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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.
Knowledge of the spatial distribution of bed lubrication regimes, i.e. frozen vs wet conditions, is crucial for understanding ice-sheet flow. Radar sounding can probe differing reflectivities between wet and frozen beds, but is limited by uncertainty in attenuation within the ice of bed echoes. Here we present two methods to estimate attenuation: (1) wide-angle radar sounding, in which source and receiver locations are varied so as to vary propagation path length, and thus echo amplitude; and (2) profiling, inwhich similar variations are obtained by sounding through varying ice thicknesses (assuming constant bed reflectivity). Siple Dome, West Antarctica, provides unusually favorable circumstances for application of these methods: the bed beneath Siple Dome is flat and uniform in its radar reflectivity, while ice thickness varies by several hundred meters. Wide-angle data 4 km from the summit yield an estimate for characteristic attenuation length of 124 m (35 dB km–1 loss), whereas profiling yields an estimate of 168 m.The difference between estimates is modest compared to the range of attenuation lengths reported in the literature. It may nonetheless prove informative by bounding effects of two ice properties to which the methods respond differently: (1) wide-angle sounding sampled relatively warm (lossy) ice beneath the summit, whereas the profiling method sampled relatively cold ice beneath the flanks as well; and (2) strain-induced crystal orientation fabrics and resulting dielectric anisotropy in the ice would vary from summit to flank, and may influence wide-angle sounding more strongly than profiling.
Brief meetings were held to confirm the elections of the incoming Division President, Francoise Genova and Vice President, Ray Norris along with the Organizing Committee which will consist of the incoming Presidents of the 7 Commissions (5,6,14,41,46,50 and 55) plus additional nominated members. The incoming Organizing Committee will thus consist of:
A coming ‘Age of Interdependent Forms’ seems destined to mark the success of what could be called ‘despecialized/interspecific fitness’ among neotenic strains (perpetuating juvenile traits) of species such as humans and domestic animals. Humans as well as the first domesticants underwent a neotenic evolution in the wild during the repeated interglacial periods which, acting on a number of mammalian forms, selected against adult species-specific ancestral adaptations to a stable environment. Neotenic species continue to look and behave more like ancestral youths than adults—even after sexual maturity and throughout their life-history. As they retain lifelong youthful dependency motivations, they can easily, under suitable conditions, become interdependent forms. By the time of melting of the last Pleistocene glacier, all the domestic partners had already become more dependency-prone than formerly, and were behaviourally despecialized enough to form the alliance that is now changing the order of Nature.