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To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes.
DELTA score development used neuropsychological test scores from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0–15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer’s biomarkers.
There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aβ SUVr (ρ = 324), higher CSF-pTau/CSF-Aβ ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer’s disease biomarker classification.
Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer’s biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Salmonella prevalence in UK pigs is amongst the highest in Europe, highlighting the need to investigate pig farms which have managed to maintain a low Salmonella seroprevalence. A total of 19 pig farms that had a consistently low (<10%) seroprevalence over 4 years (named Platinum farms) were compared against 38 randomly selected Control farms, chosen to match the same distribution of production types and geographical distribution of the Platinum farms. Each farm was visited and floor faeces and environmental samples were collected. It was shown that Control farms had a significantly higher median percentage of pooled faecal samples positive for Salmonella compared with the Platinum farms (12.1% and 0.4% for pooled faecal samples, respectively) and were more likely to have serovars of public health importance detected (S. Typhimurium/ monophasic variants or S. Enteritidis). Considering the comprehensive on-farm sampling, the identification of farms negative for Salmonella, along with the identification of those that had maintained low prevalence over a long period is important. The risk factor analyses identified pelleted feed, feed deliveries crossing farm perimeter and regular antibiotic use as associated with being a Control farm. Performance data indicated that Platinum farms were performing better for slaughter live weight than Controls. Limited assessments of available pig movement records suggested that the source of pigs was not key to Platinum status, but further study would be needed to confirm this finding. These results emphasise that maintaining very low prevalence on UK farms is achievable.
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.
Chondrichthyan teeth from a new locality in the Scottish Borders supply additional evidence of Early Carboniferous chondrichthyans in the UK. The interbedded dolostones and siltstones of the Ballagan Formation exposed along Whitrope Burn are interpreted as representing a restricted lagoonal environment that received significant amounts of land-derived sediment. This site is palynologically dated to the latest Tournaisian–early Viséan. The diverse dental fauna documented here is dominated by large crushing holocephalan toothplates, with very few, small non-crushing chondrichthyan teeth. Two new taxa are named and described. Our samples are consistent with worldwide evidence that chondrichthyan crushing faunas are common following the Hangenberg extinction event. The lagoonal habitat represented by Whitrope Burn may represent a temporary refugium that was host to a near-relict fauna dominated by large holocephalan chondrichthyans with crushing dentitions. Many of these had already become scarce in other localities by the Viséan and become extinct later in the Carboniferous. This fauna provides evidence of early endemism or niche separation within European chondrichthyan faunas at this time. This evidence points to a complex picture in which the diversity of durophagous chondrichthyans is controlled by narrow spatial shifts in niche availability over time.
The concept of information has penetrated almost all areas of human inquiry, from physics, chemistry, and engineering through biology to the social sciences. And yet its status as a physical entity remains obscure. Traditionally, information has been treated as a derived or secondary concept. In physics especially, the fundamental bedrock of reality is normally vested in the material building blocks of the universe, be they particles, strings, or fields. Because bits of information are always instantiated in material degrees of freedom, the properties of information could, it seems, always be reduced to those of the material substrate. Nevertheless, over several decades there have been attempts to invert this interdependence and root reality in information rather than matter. This contrarian perspective is most famously associated with the name of John Archibald Wheeler, who encapsulated his proposal in the pithy dictum ‘it from bit?’ (Wheeler, 1999).
In a practical, everyday sense, information is often treated as a primary entity, as a ‘thing in its own right’ with a measure of autonomy; indeed, it is bought and sold as a commodity alongside gas and steel. In the life sciences, informational narratives are indispensable: biologists talk about the genetic code, about translation and transcription, about chemical signals and sensory data processing, all of which treat information as the currency of activity, the ‘oil’ that makes the ‘biological wheels go round’. The burgeoning fields of genomic and metagenomic sequencing and bioinformatics are based on the notion that informational bits are literally vital. But beneath this familiar practicality lies a stark paradox. If information makes a difference in the physical world, which it surely does, then should we not attribute to it causal powers? However, in physics causation is invariably understood at the level of particle and field interactions, not in the realm of abstract bits (or qubits, their quantum counterparts). Can we have both? Can two causal chains coexist compatibly? Are the twin narratives of material causation and informational causation comfortable bedfellows? If so, what are the laws and principles governing informational dynamics to place alongside the laws of material dynamics?
Recent advances suggest that the concept of information might hold the key to unravelling the mystery of life's nature and origin. Fresh insights from a broad and authoritative range of articulate and respected experts focus on the transition from matter to life, and hence reconcile the deep conceptual schism between the way we describe physical and biological systems. A unique cross-disciplinary perspective, drawing on expertise from philosophy, biology, chemistry, physics, and cognitive and social sciences, provides a new way to look at the deepest questions of our existence. This book addresses the role of information in life, and how it can make a difference to what we know about the world. Students, researchers, and all those interested in what life is and how it began will gain insights into the nature of life and its origins that touch on nearly every domain of science.