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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.
Parasitic worms are amongst the most common pathogens to infect humans and have a long-established history of inflicting disease in their hosts. There is a large body of evidence that states intestine-dwelling helminths ensure their survival by influencing the host immune response against them. In recent years, it has become apparent that the large and diverse microbial communities that exist in the gastrointestinal (GI) tract of the host and within the parasite itself have a pivotal role in worm survival and persistence. Using a variety of mouse models (including laboratory, germ-free and rewilded mice), there have been new insights into how bacteria and worms interact with each other; this includes the discovery that Trichuris is unable to hatch and/or infect their host in the absence of bacteria, and that these worms contain a Trichuris-specific gut microbiota. These interactions are determined in part by the capacity of the host, gut microbiota and worms to communicate via metabolites such as butyrate, which are microbially derived and have known immunoregulatory properties. By exploring the contribution of gut bacteria to worm infections and the intricate relationship that exists between them, an exciting and emerging field in whipworm parasitology is established.
This paper considers the timing and mechanisms of deforestation in the Western Isles of Scotland, focusing in particular on the landscape around the Calanais stone circles, one of the best preserved late Neolithic/early Bronze Age monumental landscapes in north-west Europe. We present new archaeological and palaeoenvironmental evidence from a soil and peat sequence at the site of Aird Calanais, which spans the main period of use of the Calanais circles. We then draw on a new synthesis of archaeobotanical and palynological evidence from across the Western Isles and a review of comparable data from the wider North Atlantic zone, before assessing the role of early farming communities in clearing the wooded landscapes of the region. Pollen and radiocarbon dating at the site of Aird Calanais reveal that a layer of birch branches, dating to the late Neolithic (2912–2881 cal bc), was contemporaneous with a decline in woodland at the site, as well as with the major phase of Neolithic activity at the Calanais stone circle complex. However, our synthesis of the pollen and plant macrofossil evidence from across the Western Isles suggests that the picture across these islands was altogether more complex: woodlands declined both before, as well as during, the Neolithic and deciduous woodlands remained sufficiently abundant for Neolithic fuel procurement. Finally, we consider the implications of the results for understanding the interactions between first farmers and woodlands in the wider North Atlantic region.
This paper investigates Margaret Cavendish's characterization of experimental philosophers as hybrids of bears and men in her 1666 story The Description of a New World, Called the Blazing World. By associating experimental philosophers, in particular Robert Hooke and his microscope, with animals familiar to her readers from the sport of bear-baiting, Cavendish constructed an identity for the fellows of the Royal Society of London quite unlike that which they imagined for themselves. Recent scholarship has illustrated well how Cavendish's opposition to experimental philosophy is linked to her different natural-philosophical, political and anthropological ideas. My contribution to this literature is to examine the meanings both of bears in early modern England and of microscopes in experimental rhetoric, in order to illustrate the connection that Cavendish implies between the two. She parodied Hooke's idea that his microscope extended his limited human senses, and mocked his aim that by so doing he could produce useful knowledge. The bear-men reflect inhuman ambition and provide a caution against ignoring both the order of English society and the place of humans in nature.
Health benefits for man have been associated with conjugated linoleic acid (CLA) and dairy products are highlighted as offering the best opportunity to increase CLA consumption. CLA is synthesised in the rumen as an intermediate in the biohydrogenation of linoleic acid to stearic acid. The supplies of both intermediates and endproducts of biohydrogenation are affected by the substrate supply and extent of biohydrogenation, thus influencing the CLA content of milk from ruminants. The majority of CLA is present in the rumen in the form of the cis-9,trans-11 isomer. The transfer efficiency of CLA to milk fat is affected by the presence of different isomers of CLA. Ruminant mammary and adipose cells are able to synthesise cis-9,trans-11-CLA from trans-11-18:1 (vaccenic acid) by the action of the Δ9-desaturase enzyme. Plant oils are high in both linoleic and linolenic acids, which results in increased CLA production in the rumen and in the mammary gland. The CLA content of milk increases when cows are offered grazed grass. Many published studies examining the CLA concentration of processed milk were confounded by variations in the concentration of CLA in the raw milk.
As an isolated island group lying off the NW European mainland which was uninhabited until the mid-first millennium AD, the Faroes offer a unique opportunity to study natural processes of Holocene ecosystem development in a region where anthropogenic activity is usually a complicating factor. In this paper new radiocarbon dates and pollen-analytical data from the island of Sandoy, in the centre of the Faroes archipelago, are presented. Together with existing pollen and plant macrofossil records, these data allow a reconstruction of patterns of Holocene vegetational and edaphic change. Basal peat dates indicate that large areas of blanket mire were established long before the first human settlement, demonstrating conclusively that human impact is not necessary for the development of such ecosystems. The timing of the initiation of the blanket peats varies markedly, both across the Faroes as a whole and at a landscape scale, with dates distributed evenly over 9000 years. This suggests that, in the Faroes at least, pedogenesis was more important than climatic change in determining the timing of the spread of blanket peat systems.
In stably stratified flow over a three-dimensional hill, we can define a dividing streamline that separates those streamlines that pass around the hill from those that pass over the hill. The height Hs of this dividing streamline can be estimated by Sheppard's simple energy argument; fluid parcels originating far upstream of a hill at an elevation above Hs have sufficient kinetic energy to rise over the top, whereas those below Hs must pass around the sides. This prediction provides the basis for analysing an extensive range of laboratory observations and measurements of stably stratified flow over a variety of shapes and orientations of hills and with different upwind density and velocity profiles. For symmetric hills and small upwind shear, Sheppard's expression provides a good estimate for Hs. For highly asymmetric flow and/or in the presence of strong upwind shear, the expression provides a lower limit for Hs. As the hills become more nearly two-dimensional, these experiments become less well defined because steady-state conditions take progressively longer to be established. The results of new studies are presented here of the development of the unsteady flow upwind of two-dimensional hills in a finite-length towing tank. These measurements suggest that a very long tank would be required for steady-state conditions to be established upstream of long ridges with or without small gaps and cast doubt upon the validity of previous laboratory studies.
Despite their relatively small total ice volume, mid-latitude valley glaciers are expected to make a significant contribution to global sea-level rise over the next century due to the sensitivity of their mass-balance systems to small changes in climate. Here we use a degree-day model to reconstruct the past century of mass-balance variation at ‘Ka Roimata o Hine Hukatere’ Franz Josef Glacier, New Zealand, and to predict how mass balance may change over the next century. Analysis of the relationship between temperature, precipitation and mass balance indicates that temperature is a stronger control than precipitation on the mass balance of Franz Josef Glacier. The glacier’s mass balance, relative to its 1986 geometry, has decreased at a mean annual rate of 0.02m a–1 w.e. between 1894 and 2005. We compare this reduction to observations of terminus advance and retreat, of which Franz Josef Glacier has the best record in the Southern Hemisphere. For the years 2000–05 the relative mass balance ranged from –0.75 to +1.50m a–1 w.e., with 2000/01 the only year showing a negative mass balance. In a regionally downscaled Intergovernmental Panel on Climate Change mean warming scenario, the annual relative mass balance will continue to decrease at 0.02m a–1 w.e. through the next century.
The Norse colonisation or landnám of the North Atlantic islands of the Faroes, Iceland, and Greenland from the ninth century AD onwards provides opportunities to examine human environmental impacts on ‘pristine’ landscapes on an environmental gradient from warmer, more maritime conditions in the east to colder, more continental conditions in the west. This paper considers key environmental contrasts across the Atlantic and initial settlement impacts on the biota and landscape. Before landnám, the modes of origin of the biota (which resulted in boreo-temperate affinities), a lack of endemic species, limited diversity, and no grazing mammals on the Faroes or Iceland, were crucial in determining environmental sensitivity to human impact and, in particular, the impact of introduced domestic animals. Gathering new data and understanding their geographical patterns and changes through time are seen as crucial when tackling fundamental questions about human interactions with the environment, which are relevant to both understanding the past and planning for the future.
Referrals for young males with drink-related offending behaviours were obtained from local courts. Following an assessment interview, young offenders completed either a talk-based Alcohol Education Course (AEC) or a behavioural AEC. At follow-up interviews, differences in dependent variables of offending and drinking behaviour were observed. The results are discussed in the context of their possible implications for practice.
There is a need for a method, useful both to the clinician and to the research worker which can assess both the ‘quantity’ and the ‘quality’ of daily life. In this paper two ‘diary’ methods are described for obtaining accounts of daily activities, social contacts and patterns of interaction from people diagnosed as having multiple sclerosis. The information obtained is compared with that derived from a major decennial national survey of the population aged over 4 years and from a selected group of matched non-patient controls. The paper is divided into two parts, each concentrating on one of the techniques. The first is a postal 24-hour written account; the second a detailed tape-recorded interview known as the ‘Standard Day Interview’. Difficulties and advantages in using these approaches to assess both the quantitative and the qualitative changes during disabling illness are discussed and proposals for developing the methods are presented. Indications of substantive variation in the use of time by samples drawn from the ‘healthy’ and from populations with multiple sclerosis are reported.
Emotionalism, occurring as excessive or inappropriate weepiness or laughter, is a common and distressing symptom of the pseudobulbar state. It interferes with conversation, is socially embarrassing, and occurring during eating or drinking can be dangerous, particularly so in a patient already dysphagia Preliminary and uncontrolled use of imipramine in a few cases of this condition impressed us with its efficacy, and we therefore engaged in a “double-blind” form of therapeutic trial, comparing two dose strengths of imipramine with phenobarbitone and dummy tablets given in random sequence to each patient. Our favourable impression of imipramine being confirmed, we then attempted to assess the effect on this symptom of two other drugs of related pharmacology.
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