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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.
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.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
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.
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.
Ammonia was the first interstellar molecule with more than two atoms to be discovered (Cheung et al. 1968). Since that time it has been observed in many HII regions and dark clouds (Mayer et al. 1973; Morris et al. 1973; Cheung et al. 1973; Kaifu et al. 1975). The molecule has a rich rotation-inversion spectrum with about 10 transitions in the range 23-25 GHz. Each line has hyperfine structure which permits, in principle, the determination of optical depths, filling factors and excitation. Unfortunately line brightness temperatures are low (<1 K) so that a low-noise receiving system and long integration times are required to exploit these possibilities.
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.
Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of primary ciliary dyskinesia patients, but the prevalence of primary ciliary dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in primary ciliary dyskinesia and that might suggest the possibility of primary ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of primary ciliary dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive primary ciliary dyskinesia confirmed in one individual, and probable primary ciliary dyskinesia identified in two others. The high prevalence of respiratory features compatible with primary ciliary dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of primary ciliary dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a primary ciliary dyskinesia evaluation.
The reaction kinetics of depleted uranium under constant hydrogen pressure (1 bar) have been measured as a function of reaction temperatures between 65 and 385 °C for as-polished and vacuum annealed samples. Enhanced hydrogen reactivity was observed on samples that underwent vacuum annealing prior to hydrogen exposure. The enhanced reactivity was found to be the result of enhanced nucleation rates on annealed samples since the specific rate per reacting unit area remained unaffected. X-ray photoelectron spectroscopy demonstrates that the nucleation kinetics were promoted on annealed samples as a result of the dehydration and partial reduction of the UO2+x outer oxide layer and the formation of an oxycarbide (UOxCy) sub-layer.
The sequence of 165 nucleotides at the 3´ end of the 1D (VP1) gene of foot-and-mouth disease (FMD) virus was determined for 44 type Asia 1 strains isolated from throughout Asia between 1954–92. Analysis of the relationships between the virus genomes showed epidemiological links not previously evident. The possible origin of the only outbreak of FMD Asia 1 to have occurred in Europe, in Greece in 1984, was identified because the nucleotide sequence of this virus was closely-related to the sequences of those present in the Middle East between 1983–5.
Variation in the region sequenced was not as great as that seen in the other FMDV serotypes and all viruses shared greater than 85% nucleotide identity. Thus all the virus isolates examined were considered to belong to a single genotype.
A database of Asia 1 virus sequences has been established which will facilitate the rapid analysis of new outbreaks strains.
This paper compares strains of foot-and-mouth disease (FMD) serotype SAT (South African Territories) 2 viruses isolated from Zimbabwe and other African countries using monoclonal antibodies (MAb). A sandwich-ELISA was used to examine the relative binding of anti-SAT 2 MAb to the various viruses. The MAb-binding profiles of viruses isolated from field samples were compared using hierarchical cluster analysis. Viruses were obtained from game animals, mainly African buffalo (Syncerus caffer) which is the natural host and reservoir for SAT serotypes in Africa, and from cattle showing clinical signs of FMD, as well as from animals suspected of carrying the virus subclinically. Some isolates have been adapted for use as vaccine strains. The results showed that most of the Zimbabwe isolates collected between 1989 and 1992 were an antigenically closely-related group. Although differences were observed between Zimbabwe isolates collected between 1989 and 1992 and those collected in 1987, there was no correlation with the different MAb binding patterns within the 1987 group and the epidemiological information received from the field. Similar profiles were observed for many SAT 2 viruses, including viruses isolated over a 50-year period and from geographically distant areas. This indicates an inherent stability in antigenic profiles of SAT 2 viruses. The MAb panel was capable of assessing antigenic variation, since very different profiles were obtained for some isolates. The work also allowed comparison and characterization of anti-type SAT 2 MAb from different laboratories. The findings are discussed with reference to selection of vaccine strains.
Plaque purification of foot-and-mouth disease (FMD) type O viruses isolated from cattle in Saudi Arabia showed the presence of mixed serotype infections. Sixteen out of 31 samples collected between 1985 and 1991 also contained Asia 1 virus, a serotype which had previously only been isolated from a single outbreak in that country in 1980. Nucleotide sequences of the Asia 1 component of all these samples revealed little variation and showed that they were closely related to both a Russian lapinized vaccine virus strain (Asia 1/Tadzhikistan/64), and to a field isolate from Turkey (Asia 1/TUR/15/73). Although mixed FMD infections have been observed previously this is a first report of a serotype, considered to be exotic to a country, co-existing undetected for an extended period of time.
In 1986 and 1987 foot-and-mouth disease virus (FMDV) serotype A was isolated from outbreaks of disease in Saudi Arabia and Iran. Selected virus isolates were antigenically distinct from the prototype A22 virus strain (A22/Iraq/64), but were serologically related to each other. However, polyacrylamide gel electrophoresis showed that whilst the respective Saudi Arabian structural polypeptides were homogeneous, those from an Iran isolate were distinct. Direct sequencing of part of the P-1D (VP1) gene demonstrated considerable difference in nucleotide homology between the two groups of viruses; the Saudi Arabian viruses were closely related to each other but only distantly related to both the A22 prototype virus strain and the Iranian virus isolate. The latter viruses were only slightly more closely related to each other. Thus there appeared to be at least two distinct FMDV type A variants co-circulating in the Middle East, both of which differed considerably from the classical A22 subtype.