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Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
Terrestrial plant macrofossils from the sedimentary record of Lake Suigetsu, Japan, provide the only quasi-continuous direct atmospheric record of radiocarbon (14C) covering the last 50 ka cal BP (Bronk Ramsey et al. 2012). Since then, new high precision data have become available on U-Th dated speleothems from Hulu Cave China, covering the same time range (Cheng et al. 2018). In addition, an updated varve-based chronology has also been published for the 2006 core from Lake Suigetsu (SG06) based on extended microscopic analysis of the sediments and improved algorithms for interpolation (Schlolaut et al. 2018). Here we reanalyze the radiocarbon dataset from Suigetsu based on the new varve counting information and the constraints imposed by the speleothem data. This enables the new information on the calendar age scale of the Suigetsu dataset to be used in the construction of the consensus IntCal calibration curve. Comparison of the speleothem and plant macrofossil records provides insight into the mechanisms underlying the incorporation of carbon into different types of record and the relative strengths of different types of archive for calibration purposes.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
We use cyclic charge-discharge experiments to evaluate the capacity retention rates of two quinone-bromide flow batteries (QBFBs). These aqueous QBFBs use a negative electrolyte containing either anthraquinone-2,7-disulfonic acid (AQDS) or anthraquinone-2-sulfonic acid (AQS) dissolved in sulfuric acid, and a positive electrolyte containing bromine and hydrobromic acid. We find that the AQS cell exhibits a significantly lower capacity retention rate than the AQDS cell. The observed AQS capacity fade is corroborated by NMR evidence that suggests the formation of hydroxylated products in the electrolyte in place of AQS. We further cycle the AQDS cell and observe a capacity fade rate extrapolating to 30% loss of active species after 5000 cycles. After about 180 cycles, bromine crossover leads to sufficient electrolyte imbalance to accelerate the capacity fade rate, indicating that the actual realization of long cycle life will require bromine rebalancing or a membrane less permeable than Nafion® to molecular bromine.
The Inquisitions post mortem (IPMs) are a truly wonderful source for many different aspects of late medieval countryside and rural life. They have recently been made digitally accessible and interrogatable by the Mapping the Medieval Countryside project, and the first fruits of these developments are presented here. The chapters examine IPMs in connection with the landscape and topography of England, in particular markets and fairs and mills; and consider the utility of proofs of age for everyday life on such topics as the Church, retaining, and the wine trade.
Michael Hicks is Emeritus Professor of Medieval History at the University of Winchester.
Contributors: Katie A. Clarke, William S. Deller, Paul Dryburgh, Christopher Dyer, Janette Garrett, Michael Hicks, Matthew Holford, Gordon McKelvie, Stephen Mileson, Simon Payling, Matthew Tompkins, Jennifer Ward.
Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months.
We describe a versatile infrared camera/spectrograph, IRIS, designed and constructed at the Anglo-Australian Observatory for use on the Anglo-Australian Telescope. A variety of optical configurations can be selected under remote control to provide several direct image scales and a few low-resolution spectroscopic formats. Two cross-dispersed transmission echelles are of novel design, as is the use of a modified Bowen-Burch system to provide a fast f/ratio in the widest-field option. The drive electronics includes a choice of readout schemes for versatility, and continuous display when the array is not taking data, to facilitate field acquisition and focusing.
The linearity of the detector has been studied in detail. Although outwardly good, slight nonlinearities prevent removal of fixed-pattern noise from the data without application of a cubic linearising function.
Specific control and data-reduction software has been written. We describe also a scanning mode developed for spectroscopic imaging.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.
Background: Delirium is common in critically ill patients and its presence is associated with increased mortality and increased likelihood of poor cognitive function among survivors. However, the cause of delirium is unknown. The purpose of this study was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to assess brain tissue oxygenation in patients with septic shock, who are at high risk of developing delirium. Methods: This prospective observational study was conducted in a 33-bed general medical surgical intensive care unit (ICU). Patients with severe sepsis or septic shock were eligible for recruitment. The FORESIGHT NIRS monitor was used to assess brain tissue oxygenation in the frontal lobes for the first 72 hours of ICU admission. Physiological data was also recorded. We used the Confusion Assessment Method-ICU to screen for delirium.Results: From March 1st 2014-September 30th 2014, 10 patients with septic shock were recruited. The NIRS monitor captured 81% of the available data. No adverse events were recorded. Brain tissue oxygenation demonstrated significant intra- and inter-individual variability in the way it correlated with physiological parameters, such as mean arterial pressure, heart rate, and peripheral oxygen saturation. Mean brain tissue oxygen levels were significantly lower in patients who were delirious for the majority of their ICU stay. Conclusion: It is feasible to record brain tissue oxygenation with NIRS in patients with septic shock. This study provides the infrastructure necessary for a larger prospective observational study to further examine the relationship between brain tissue oxygenation, physiological parameters, and acute neurological dysfunction.