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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.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
The best method for quantifying the marine reservoir effect (MRE) using the global IntCal Marine13 calibration curve remains unresolved. Archaeologists frequently quantify uncertainty on MRE values as errors computed from single pairs of marine-terrestrial radiocarbon ages, which we argue significantly overstates their accuracy and precision. Here, we review the assumptions, methods, and applications of estimating MRE via an estimate of the additional regional offset between the marine and terrestrial calibration curves (ΔR) for the Prince Rupert Harbour (PRH) region of British Columbia, Canada. We acknowledge the influence on ΔR of MRE variation as (1) a dynamic oceanographic process, (2) its variable expression in biochemical and geochemical pathways, and (3) compounding errors in sample selection, measurement, and calculation. We examine a large set of marine-terrestrial pairs (n = 63) from PRH to compare a common archaeological practice of estimating uncertainty from means that generate an uncertainty value of ±49 years with a revised, more appropriate estimate of error of ± 230 years. However, we argue that the use of multiple-pair samples estimates the PRH ΔR as 273 ± 38 years for the last 5,000 years. Calculations of error that do not consider these issues may generate inaccurate age estimates with unjustifiable precision.
Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland.
Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009–2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017.
Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78–1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76–1.10) and 18.8% (OR = 0.81, 0.67–0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63–1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89–2.32) increased, and 4.3% (OR = 0.96, 0.56–1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80–2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41–3.11) increase in odds of incident anxiety.
High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose–response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.
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.
Prince Rupert Harbour (PRH), on the north Pacific Coast of British Columbia, contains at least 157 shell middens, of which 66 are known villages, in an area of approximately 180 km2. These sites span the last 9500 yr and in some cases are immense, exceeding 20,000 m2 surface area and several meters in depth. Recent archaeological research in PRH has become increasingly reliant on radiocarbon dates from marine shell for developing chronologies. However, this is problematic as the local marine reservoir effect (MRE) remains poorly understood in the region. To account for the MRE and to better date the Harbour’s sites, we propose a ΔR of 273±38 for the PRH area, based on our work at the site of Kitandach (GbTo-34), a massive shell midden-village centrally located within the Harbour. We followed the multiple paired sample approach for samples from specific contexts and ensured contemporaneity within the groups of marine and terrestrial materials by statistically assessing for outliers using the χ2 test. Taking together, the results for this and previous studies, it appears the MRE was fairly constant over the past 5000 yr.
We study a first-order functional language with the novel combination of the ideas of refinement type (the subset of a type to satisfy a Boolean expression) and type-test (a Boolean expression testing whether a value belongs to a type). Our core calculus can express a rich variety of typing idioms; for example, intersection, union, negation, singleton, nullable, variant, and algebraic types are all derivable. We formulate a semantics in which expressions denote terms, and types are interpreted as first-order logic formulas. Subtyping is defined as valid implication between the semantics of types. The formulas are interpreted in a specific model that we axiomatize using standard first-order theories. On this basis, we present a novel type-checking algorithm able to eliminate many dynamic tests and to detect many errors statically. The key idea is to rely on a Satisfiability Modulo Theories solver to compute subtyping efficiently. Moreover, using a satisfiability modulo theories solver allows us to show the uniqueness of normal forms for non-deterministic expressions, provide precise counterexamples when type-checking fails, detect empty types, and compute instances of types statically and at run-time.
The assumption that the transmission of social behaviors and political preferences is purely cultural has been challenged repeatedly over the last 40 years by the combined evidence of large studies of adult twins and their relatives, adoption studies, and twins reared apart. Variance components and path modeling analyses using data from extended families quantified the overall genetic influence on political attitudes, but few studies have attempted to localize the parts of the genome which accounted for the heritability estimates found for political preferences. Here, we present the first genome-wide analysis of Conservative-Liberal attitudes from a sample of 13,000 respondents whose DNA was collected in conjunction with a 50-item sociopolitical attitude questionnaire. Several significant linkage peaks were identified and potential candidate genes discussed.
Cerebral palsy (CP) is the most common cause of severe physical disability in childhood. Spastic hemiplegia, characterized by motor impairments largely affecting one side of the body, is the most common form of CP. The resulting impaired hand function is one of the most disabling symptoms of hemiplegia, affecting self-care activities such as feeding, dressing and grooming. Consequently, children with hemiplegic CP tend not to use the more affected extremity. This “developmental non-use” can lead to further deficits, most notably affecting bimanual coordination. To date, there is unfortunately little evidence of efficacy of any specific treatment approach. Nevertheless, several lines of evidence suggest the impairments are not static. Upper extremity performance in children with CP may improve with practice and development, indicating that hand function may well be amenable to treatment. In this chapter we review this evidence along with studies involving intensive unilateral practice; i.e. constraint-induced movement therapy (CIMT). We then discuss important limitations of CIMT (most importantly, bimanual impairments underlie functional limitations) and introduce a new form of intensive training to address these limitations: Hand–Arm Bimanual Intensive Training (HABIT). The clinical implications of these findings and future directions for pediatric rehabilitation research are discussed.
Cerebral palsy (CP) is a development disorder of movement and posture causing limitations in activity and deficits in motor skill (Bax et al., 2005) and is attributed to non-progressive disturbances in the developing fetal or infant brain.
When transporting an object during locomotion, the inertial forces that are indirectly generated through the motion of multiple body parts must be taken into account to prevent object slippage. The grip–inertial force coupling that maintains a secure grasp on a hand-held object is preserved across a variety of locomotor tasks that include variations in velocity and precision demands (e.g. transporting a cup of water). When the locomotor pattern is altered by changing the step length or stepping over an obstacle, the grip–inertial force coupling continues to be under anticipatory control. However, the coupling is less robust and can be explained by increased attention demands. Furthermore, the fine motor grasping functions and gross motor locomotor functions are precisely coordinated across multiple limb segments to ensure successful performance right from the onset of gait initiation. These findings support the notion that grip force is based on moment-to-moment predictions of inertial forces acting on the object at gait initiation and throughout predictable variations in the gait cycle. Internal representations of the interactions between body segments through which inertia is transferred to the object–digit interface are proposed to provide the basis for this anticipatory grip force control.
A central question in the study of systems motor control is how simultaneous tasks involving multiple body segments are coordinated. For example, during voluntary movements with a hand-held object, grip (normal) force is coupled to the object's load as well as to the motion-induced inertial (tangential) force in an anticipatory manner to prevent slippage.
Antidepressants are important in the treatment of depression, and selective serotonin reuptake inhibitors are first-line pharmacologic options. However, only 50% to 70% of patients respond to first treatment and <40% remit. Since depression is associated with substantial morbidity, mortality, and family burden, it is unfortunate and demanding on health resources that patients must remain on their prescribed medications for at least 4 weeks without knowing whether the particular antidepressant will be effective. Studies have suggested a number of predictors of treatment response, including clinical, psychophysiological, neuroimaging, and genetics, each with varying degrees of success and nearly all with poor prognostic sensitivity and specificity. Studies are yet to be conducted that use multiple measures from these different domains to determine whether sensitivity and specificity can be improved to predict individual treatment response. It is proposed that a focus on standardized testing methodologies across multiple testing modalities and their integration will be crucial for translation of research findings into clinical practice.