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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.
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
Impairment in financial capacity is an early sign of cognitive decline and functional impairment in late life. Cognitive impairments such as executive dysfunction are well documented in late-life major depression; however, little progress has been made in assessing associations of these impairments with financial incapacity.
Participants included 95 clinically depressed and 41 nondepressed older adults without dementia. Financial capacity (assessed with the Managing Money scale of the Independent Living Scale), cognitive functioning (comprehensive neuropsychological evaluation), and depression severity (Hamilton Depression Rating Scale – 24) were assessed. T tests were used to assess group differences. Linear regression was used to analyze data.
Depressed participants performed significantly lower on financial capacity (t = 2.98, p < .01). Among depressed participants, executive functioning (B = .24, p < .05) was associated with reduced financial capacity, controlling for age, gender, education, depression severity, and other cognitive domains.
Our results underscore the importance of assessing financial capacity in older depressed adults as they are likely vulnerable to financial abuse even in the absence of dementia. It will be valuable to assess whether treatment for depression is an effective intervention to improve outcomes.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
High purity UO2 powder samples were subjected to accelerated aging under controlled conditions with relative humidity ranging from 34% to 98%. Characterization of the chemical speciation of the products was accomplished using X-ray photoelectron spectroscopy (XPS). A shift to higher uranium oxidation states was found to be directly correlated to increased relative humidity exposure. Additionally, the relative abundance of O2-, OH-, and H2O was found to vary with exposure time. Thus, it is expected that uranium oxide materials exposed to high relative humidity conditions during processing and storage would display a similar increase in average uranium valence.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
This chapter addresses the metabolic sequelae of maternal obesity, and by detailing effects on glucose, lipid, and protein metabolism, parallels with type 2 diabetes are highlighted. In normal pregnancy, dynamic changes in maternal glucose homeostasis and insulin sensitivity accompany the alterations in lipid and protein metabolism. Pre-existing diabetes and poor maternal glycemic control have classically been associated with adverse pregnancy outcome. Lifestyle intervention is now a critical component of the treatment strategy for diabetes, hypertension, cardiovascular disease, and obesity in non-pregnant patients. Epidemiological studies have suggested that physical activity prior to and during pregnancy may significantly reduce the risk of gestational diabetes. Some preliminary evidence suggests that combining simple maternal demographic and clinical characteristics will allow detection rates similar to those for type 2 diabetes, but external validation is still required. The maternal obesity epidemic has stimulated the need for development of effective interventions to improve pregnancy outcome.
This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11)