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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.
Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.
In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.
Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.
Besides affective instability and identity diffusion, disturbances in social interactions are a core symptom of borderline personality disorder (BPD). Interpersonal problems in BPD have been suggested to be associated with oxytocin dysregulation. To directly address this hypothesis, we investigated oxytocin plasma levels during a social exclusion (ostracism) paradigm in female BPD patients.
Twenty-two female BPD patients (diagnosed according to DSM-IV) and twenty-one healthy controls matched for gender, age, and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball paradigm, a virtual balltossing game that evokes a social exclusion situation. Emotional reactions were assessed and oxytocin and cortisol levels measured at baseline and 5, 15, and 40 min after Cyberball.
After social exclusion, oxytocin plasma levels were lower in BPD patients than in healthy controls, whereas cortisol levels did not differ between groups. BPD patients showed distinct differences in emotion regulation compared to healthy participants and reacted to social exclusion with an increase of other-focused negative emotions, particularly anger and contempt.
Our pilot study suggests that the oxytocin system shows a differential response to social exclusion in BPD patients compared to healthy controls. This difference may be related to the high rejection sensitivity of BPD patients and their difficulties in resolving social conflict.
Ostracism (social exclusion) has been found to be a remarkable stress factor to mentally ill people with difficulties in situations of social interaction. In an earlier study it was found that patients with borderline personality disorder (BPD) showed differences in oxytocin dysregulation by having lower oxytocin plasma levels during a social exclusion paradigm (Jobst et al., 2013, submitted). To our knowledge, this is the first study investigating neuroendocrinological changes of social exclusion in chronically depressed patients. Chronic depression (CD) is associated with poor social functioning and behavioral interpersonal problems which are considered to be based on the non-responsiveness of CD patients to environmental consequences.
To manipulate a situation of social exclusion we used the Cyberball Paradigm, a virtual ball tossing game which has been well validated and applied in numerous previous studies on the effects of social exclusion. 19 CD patients (according to DSM-IV) and 19 healthy controls matched for gender, age and education underwent repeated neuroendocrine measurements in a standardized laboratory setting during the Cyberball Paradigm. Assessments of psychological variables as well as measurements of oxytocin plasma levels were performed at baseline, 5 min, 15 min and 40 min after Cyberball.
As an association of interpersonal problems in BPD with oxytocin dysregulation has been found, we suggest differences in changes of oxytocin levels in a social exclusion situation in CD patients versus healthy subjects. The data will be presented and discussed in relation to specific interpersonal problems of patients suffering from CD.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Human mesenchymal stem cells were reseeded in decellularized human bone subject to a controlled mechanical loading to create a bone-on-chip that was cultured for over 26 months. The cell morphology and their secretome were characterized using immunohistochemistry and in situ immunofluorescence under confocal microscopy. The presence of stem cell derived osteocytes was confirmed at 547 days. Different cell populations were identified. Some cells were connected by long processes and formed a network. Comparison of the MSCs in vitro reorganization and calcium response to in situ mechanical stimulation were compared to MLOY4 cells reseeded on human bone. The bone-on-chip produced an ECM of which the strength was nearly a quarter of native bone after 109 days and that contained calcium minerals at 39 days and type I collagen at 256 days. The cytoplasmic calcium concentration variations seemed to adapt to the expected in vivo mechanical load at the successive stages of cell differentiation in agreement with studies using fluid shear flow stimulation. Some degree of bone-like formation over a long period of time with the formation of a newly formed matrix was observed.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
The SkyMapper 1.3 m telescope at Siding Spring Observatory has now begun regular operations. Alongside the Southern Sky Survey, a comprehensive digital survey of the entire southern sky, SkyMapper will carry out a search for supernovae and other transients. The search strategy, covering a total footprint area of ~2 000 deg2 with a cadence of ⩽5 d, is optimised for discovery and follow-up of low-redshift type Ia supernovae to constrain cosmic expansion and peculiar velocities. We describe the search operations and infrastructure, including a parallelised software pipeline to discover variable objects in difference imaging; simulations of the performance of the survey over its lifetime; public access to discovered transients; and some first results from the Science Verification data.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Anxiety sensitivity (AS), the belief that anxious arousal is harmful, is a malleable risk factor that has been implicated in anxiety and depression symptoms in adolescents. Although there is some evidence that adolescents possess distinct developmental trajectories, few studies have explored this topic. This study examined the developmental trajectory of AS in 248 adolescents (M age = 11.0 years, SD = 0.82; 56% male) across 6 years, beginning when children were age 11. This study also examined the influence of AS trajectories on anxiety and depression at age 16. Finally, this study examined the utility of AS classes in identifying anxiety and depression growth. Three AS classes were found, described by normative-stable, high-stable, and high-unstable trajectories. Adolescents in the high-stable and the high-unstable AS classes had higher levels of anxiety and depression at age 16 than did adolescents in the normative-stable AS class. In addition, the anxiety and depression trajectories fit by AS class mirrored the AS class trajectories. These findings suggest three AS trajectories can be identified in adolescents. These trajectories are discussed in relation to a developmental perspective of AS.
Exposure to animal livestock has been linked to zoonotic transmission, especially of gastrointestinal pathogens. Exposure to animals may contribute to chronic asymptomatic intestinal infection, environmental enteropathy and child under-nutrition in low-income settings. We conducted a cohort study to explore the effect of exposure to cows on growth and endemic diarrhoea in children aged <5 years in a rural, low-income setting in the Indian state of Odisha. The study enrolled 1992 households with 2739 children. Height measurements were available for 824 children. Exposure to cows was measured as (1) the presence of a cowshed within or outside the compound, (2) the number of cows owned by a household, and (3) the number of cowsheds located within 50 m of a household. In a sub-study of 518 households, fly traps were used to count the number of synanthropic flies that may act as vectors for gastrointestinal pathogens. We found no evidence that environmental exposure to cows contributes to growth deficiency in children in rural India, neither directly by affecting growth, nor indirectly by increasing the risk of diarrhoea. We found no strong evidence that the presence of a cowshed increased the number synanthropic flies in households.
Analytical transmission electron microscopy (ATEM) offers great flexibility in identification of the structural—chemical organization of soft materials at the level of individual macromolecules. However, the determination of mechanical characteristics such as hardness/elasticity of the amorphous and polycrystalline organic substances by ATEM has been problematic so far. Here, we show that energy filtered TEM (EFTEM) measurements enable direct identification and study of mechanical properties in complex (bio-)polymer systems of relevance for different industrial and (bio-)medical applications. We experimentally demonstrate strong correlations between hardness/elasticity of different polymers (polycaprolactone, polylactid, polyethelene, etc.) and their volume plasmon energy. Thickness and anisotropy effects, which substantially mask the material contrast in EFTEM bulk plasmon images, can be adequately removed by normalizing the latter by carbon elemental map. EFTEM data has been validated using atomic force microscopy phase images, where phase shift related to the hardness and elastic modulus of the materials.
Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50–64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18 : 1t), 18 : 1 Δ6-10t, vaccenic acid (18 : 1 Δ11t) and rumenic acid (18 : 2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18 : 1t was 1·52 % (90 % central range 0·98, 2·19) in men and 1·47 % (1·01, 2·19) in women. No significant associations were observed between the proportions of total 18 : 1t, 18 : 1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population.