Longitudinal Profiles of Girls' Irritable, Defiant and Antagonistic Oppositional Symptoms: Evidence for Group Based Differences in Symptom Severity

Three subdimensions of ODD symptoms have been proposed -angry/irritable (IR), argumentative/defiant (DF) and antagonism (AN). This study tested whether longitudinal symptom trajectories could be identified by these subdimensions. Group-based trajectory analysis was used to identify developmental trajectories of IR, DF and AN symptoms. Multi-group trajectory analysis was then used to identify how subdimension trajectories were linked together over time. Data were drawn from the Pittsburgh Girls Study (PGS; N = 2450), an urban community sample of girls between the ages of five--eight at baseline. We included five waves of annual data across ages five-13 to model trajectories. Three trajectories were identified for each ODD subdimension: DF and AN were characterized by high, medium and low severity groups; IR was characterized by low, medium stable, and high increasing groups. Multi-trajectory analysis confirmed these subdimensions were best linked together based on symptom severity. We did not identify girls' trajectory groups that were characterized predominantly by a particular subdimension of ODD symptoms. Membership in more severe symptom groups was significantly associated with worse outcomes five years later. In childhood and early adolescence girls with high levels of ODD symptoms can be identified, and these youth are characterized by a persistently elevated profile of IR, DF and AN symptoms. Further studies in clinical samples are required to examine the ICD-10 proposal that ODD with irritability is a distinct or more severe form of ODD

Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics

On the trade-off between efficiency in job assignment and turnover: the role of breakup fees

We highlight a novel trade-off with the use of breakup fees in employment contracts. Under asymmetric learning about workers’ productivity, the market takes job assignments (or “promotions”) as a signal of quality and bids up the wages of a promoted worker, leading to inefficiently few promotions (Waldman, M. 1984. “Job Assignments, Signalling, and Efficiency” 15 RAND Journal of Economics 255–67). Breakup fees can mitigate such inefficiencies by shielding the firm from labor-market competition, but they reduce turnover efficiency when there are firm-specific matching gains. We show that it is optimal to use breakup fees if and only if the difference between the worker’s expected productivity in the pre- and post-promotion jobs is small. Also, the relationship between the optimality of breakup fees and the importance of firm-specific human capital is more nuanced than what the extant literature may suggest

External validation of a bifactor model of oppositional defiant disorder

Dimensions of irritability and defiant behavior, though correlated within the structure of ODD, convey separable developmental risks through adolescence and adulthood. Irritability predicts depression and anxiety, whereas defiant behavior is a precursor to antisocial outcomes. Previously we demonstrated that a bifactor model comprising irritability and defiant behavior dimensions, in addition to a general factor, provided the best-fitting structure of ODD symptoms in five large datasets. Herein we extend our previous work by externally validating the bifactor model of ODD using multiple regression and multivariate behavior genetic analyses. We used parent ratings of DSM IV ODD symptoms, and symptom dimensions for ADHD (i.e., inattention and hyperactivity−impulsivity), conduct disorder (CD), depression/dysthymia, and generalized anxiety disorder (GAD) from 846 6−18-year-old twin pairs. We found that the ODD irritability factor was associated only with depression/dysthymia and GAD and the ODD defiant behavior factor was associated only with inattention, hyperactivity−impulsivity, and CD, whereas the ODD general factor was associated with all five symptom dimensions. Multivariate behavior genetic analyses found all five symptom dimensions shared genetic influences in common with the ODD general, irritability, and defiant behavior factors. In contrast, the defiant behavior factor shared genetic influences uniquely with inattention and hyperactivity−impulsivity, whereas the irritability factor shared genetic influences uniquely with depression/dysthymia and GAD, but not vice versa. This suggests that genes that influence irritability in early childhood also predispose to depression and anxiety in adolescence and adulthood. These multivariate genetic findings also support the external validity of the three ODD dimensions at the etiological level. Our study provides additional support for subtyping ODD based on these symptom dimensions, as in the revisions in the ICD-11, and suggests potential mechanisms underlying the development from ODD to behavioral or affective disorders

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio

Revisiting Event Horizon Finders

Event horizons are the defining physical features of black hole spacetimes, and are of considerable interest in studying black hole dynamics. Here, we reconsider three techniques to localise event horizons in numerical spacetimes: integrating geodesics, integrating a surface, and integrating a level-set of surfaces over a volume. We implement the first two techniques and find that straightforward integration of geodesics backward in time to be most robust. We find that the exponential rate of approach of a null surface towards the event horizon of a spinning black hole equals the surface gravity of the black hole. In head-on mergers we are able to track quasi-normal ringing of the merged black hole through seven oscillations, covering a dynamic range of about 10^5. Both at late times (when the final black hole has settled down) and at early times (before the merger), the apparent horizon is found to be an excellent approximation of the event horizon. In the head-on binary black hole merger, only {\em some} of the future null generators of the horizon are found to start from past null infinity; the others approach the event horizons of the individual black holes at times far before merger.Comment: 30 pages, 15 figures, revision

The Subluminous and Peculiar Type Ia Supernova PTF09dav

PTF09dav is a peculiar subluminous type Ia supernova (SN) discovered by the Palomar Transient Factory (PTF). Spectroscopically, it appears superficially similar to the class of subluminous SN1991bg-like SNe, but it has several unusual features which make it stand out from this population. Its peak luminosity is fainter than any previously discovered SN1991bg-like SN Ia (M_B -15.5), but without the unusually red optical colors expected if the faint luminosity were due to extinction. The photospheric optical spectra have very unusual strong lines of Sc II and Mg I, with possible Sr II, together with stronger than average Ti II and low velocities of ~6000 km/s. The host galaxy of PTF09dav is ambiguous. The SN lies either on the extreme outskirts (~41kpc) of a spiral galaxy, or in an very faint (M_R>-12.8) dwarf galaxy, unlike other 1991bg-like SNe which are invariably associated with massive, old stellar populations. PTF09dav is also an outlier on the light-curve-width--luminosity and color--luminosity relations derived for other sub-luminous SNe Ia. The inferred 56Ni mass is small (0.019+/-0.003Msun), as is the estimated ejecta mass of 0.36Msun. Taken together, these properties make PTF09dav a remarkable event. We discuss various physical models that could explain PTF09dav. Helium shell detonation or deflagration on the surface of a CO white-dwarf can explain some of the features of PTF09dav, including the presence of Sc and the low photospheric velocities, but the observed Si and Mg are not predicted to be very abundant in these models. We conclude that no single model is currently capable of explaining all of the observed signatures of PTF09dav.Comment: Accepted for publication in Ap

Neural substrates of cue reactivity and craving in Gambling Disorder

Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in Gambling Disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with Gambling Disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional MRI scan performed ~2-3 hours after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity, and associations with block-by-block craving ratings. Craving ratings in the participants with Gambling Disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the Gambling Disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with Gambling Disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial PFC. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with Gambling Disorder (compared to controls), providing support for the incentive sensitisation theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.This study was funded by the Medical Research Council—MRC G1002226 (Nutt) and G1100554 (Clark). We wish to thank the study participants and the clinical team at Imanova, Centre for Imaging Sciences. The research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. SPS was funded by the Cambridge Home Scholarship Scheme (CHSS)