Elevated Familial Cardiovascular Burden Among Adolescents With Familial Bipolar Disorder

Background: Bipolar disorder (BD) is one of the most heritable medical conditions, and certain phenotypic characteristics are especially familial in BD. BD is also strongly associated with elevated and premature cardiovascular disease (CVD) morbidity and mortality. Thus, far, little is known regarding the familiality of cardiovascular risk in BD. We therefore examined the extent of CVD-related conditions among relatives of: adolescents with BD with a family history of BD (familial BD), adolescents with BD without a family history of BD (non-familial BD) and healthy controls (HC).Materials and Methods: The sample included 372 adolescents; 75 with familial BD, 96 with non-familial BD, and 201 HC. Parents of the adolescents completed the CARDIA Family Medical History interview regarding the adolescents' first- and second- degree adult relatives. We computed a “cardiovascular risk score” (CRS) for each relative, based on the sum of the presence of diabetes, hypertension, obesity, dyslipidemia, stroke, angina, and myocardial infarction (range 0–7). Primary analyses examined for group differences in mean overall CRS scores among first and second- degree relatives combined, controlling for age, sex, and race. Secondary analyses examined first- and second-degree relatives separately, controlling for age, sex, and race.Results: There were significant between-group differences in CRS in first- and second- degree relatives combined, following the hypothesized ordering: CRS was highest among adolescents with familial BD (1.14 ± 0.78), intermediate among adolescents with non-familial BD (0.92 ± 0.79) and lowest in HC (0.76 ± 0.79; F = 6.23, df = 2, p = 0.002, ηp2 = 0.03). There was a significant pairwise difference between adolescents with familial BD and HC (p = 0.002, Cohen's d = 0.49). A similar pattern of between-group differences was identified when first-degree and second-degree relatives were examined separately.Limitations: familial cardiovascular burden was determined based on parent interview, not evaluated directly.Conclusions: Adolescents with BD with a family history of BD have elevated rates of CVD-related conditions among their relatives. This may be related to genetic overlap between BD and CVD-related conditions, shared environmental factors that contribute to both BD and CVD-related conditions, or a combination of these factors. More research is warranted to better understand the interaction between familial risk for BD and CVD, and to address this risk using family-wide preventive approaches

Galactic Spiral Structure

We describe the structure and composition of six major stellar streams in a population of 20 574 local stars in the New Hipparcos Reduction with known radial velocities. We find that, once fast moving stars are excluded, almost all stars belong to one of these streams. The results of our investigation have lead us to re-examine the hydrogen maps of the Milky Way, from which we identify the possibility of a symmetric two-armed spiral with half the conventionally accepted pitch angle. We describe a model of spiral arm motions which matches the observed velocities and composition of the six major streams, as well as the observed velocities of the Hyades and Praesepe clusters at the extreme of the Hyades stream. We model stellar orbits as perturbed ellipses aligned at a focus in coordinates rotating at the rate of precession of apocentre. Stars join a spiral arm just before apocentre, follow the arm for more than half an orbit, and leave the arm soon after pericentre. Spiral pattern speed equals the mean rate of precession of apocentre. Spiral arms are shown to be stable configurations of stellar orbits, up to the formation of a bar and/or ring. Pitch angle is directly related to the distribution of orbital eccentricities in a given spiral galaxy. We show how spiral galaxies can evolve to form bars and rings. We show that orbits of gas clouds are stable only in bisymmetric spirals. We conclude that spiral galaxies evolve toward grand design two-armed spirals. We infer from the velocity distributions that the Milky Way evolved into this form about 9 Gyrs ago.Comment: Published in Proc Roy Soc A. A high resolution version of this file can be downloaded from http://papers.rqgravity.net/SpiralStructure.pdf. A simplified account with animations begins at http://rqgravity.net/SpiralStructur

Conditions for the Quantum to Classical Transition: Trajectories vs. Phase Space Distributions

We contrast two sets of conditions that govern the transition in which classical dynamics emerges from the evolution of a quantum system. The first was derived by considering the trajectories seen by an observer (dubbed the ``strong'' transition) [Bhattacharya, et al., Phys. Rev. Lett. 85: 4852 (2000)], and the second by considering phase-space densities (the ``weak'' transition) [Greenbaum, et al., Chaos 15, 033302 (2005)]. On the face of it these conditions appear rather different. We show, however, that in the semiclassical regime, in which the action of the system is large compared to $\hbar$, and the measurement noise is small, they both offer an essentially equivalent local picture. Within this regime, the weak conditions dominate while in the opposite regime where the action is not much larger than Planck's constant, the strong conditions dominate.Comment: 8 pages, 2 eps figure

An electron Talbot interferometer

The Talbot effect, in which a wave imprinted with transverse periodicity reconstructs itself at regular intervals, is a diffraction phenomenon that occurs in many physical systems. Here we present the first observation of the Talbot effect for electron de Broglie waves behind a nanofabricated transmission grating. This was thought to be difficult because of Coulomb interactions between electrons and nanostructure gratings, yet we were able to map out the entire near-field interference pattern, the "Talbot carpet", behind a grating. We did this using a Talbot interferometer, in which Talbot interference fringes from one grating are moire'-filtered by a 2nd grating. This arrangement has served for optical, X-ray, and atom interferometry, but never before for electrons. Talbot interferometers are particularly sensitive to distortions of the incident wavefronts, and to illustrate this we used our Talbot interferometer to measure the wavefront curvature of a weakly focused electron beam. Here we report how this wavefront curvature demagnified the Talbot revivals, and we discuss applications for electron Talbot interferometers.Comment: 5 pages, 5 figures, updated version with abstrac

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Aging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Aging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective

Effects of comorbid anxiety disorders on the longitudinal course of pediatric bipolar disorders

OBJECTIVE: To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP). METHOD: As part of the Course and Outcome of Bipolar Youth study, 413 youth, who were 7 through 17 years or age and who met criteria for DSM-IV BP-I (n = 244), BP-II (n = 28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n = 141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed. RESULTS: At intake and during the follow-up, 62% of youth with BP met criteria for at least 1 anxiety disorder. About 50% of the BP youth with anxiety had ≥2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with ≥2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety. CONCLUSIONS: Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, and more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youth with anxiety are warranted

Cognitive flexibility and performance in children and adolescents with threshold and sub-threshold bipolar disorder

Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or “not otherwise specified” (NOS) participating in multi-site Course and Outcome of Bipolar Youth study compared to typically developing controls (TDC) without psycho-pathology. In particular, we sought to test the hypothesis that BD-I and BD-II youths with full threshold episodes of mania or hypomania would have cognitive deficits, including in reversal learning, vs. those BD-NOS participants with sub-threshold episodes and TDCs. N = 175 participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of the simple reversal stage of the CANTAB intra-/extra-dimensional shift task showed that aggregated BD-I/II participants required significantly more trials to complete the task than either BD-NOS participants with sub-syndromal manic/hypomanic symptoms or than TDCs. BD participants across sub-types had impairments in sustained attention and information processing for emotionally valenced words. Our results align with prior findings showing that BD-I/II youths with distinct episodes have specific alterations in reversal learning. More broadly, our study suggests that further work is necessary to see the interaction between neurocognitive performance and longitudinal illness course. Additional work is required to identify the neural underpinnings of these differences as targets for potential novel treatments, such as cognitive remediation

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients

Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD)

Longitudinal Associations Between Interpersonal Relationship Functioning and Mood Episode Severity in Youth With Bipolar Disorder

This study examined the longitudinal association between mood episode severity and relationships in BP youth. Participants were 413 Course and Outcome of Bipolar Youth study youth, aged 12.6 ± 3.3 years. Monthly ratings of relationships (parents, siblings, and friends) and mood episode severity were assessed by the Adolescent Longitudinal Interval Follow-Up Evaluation (ALIFE) Psychosocial Functioning Schedule (PFS) and Psychiatric Rating Scales (PSR) on average every 8.2 months over 5.1 years. Correlations examined whether participants with increased episode severity also reported poorer relationships, and also examined whether fluctuations in episode severity predicted fluctuations in relationships, and vice versa. Results indicated that participants with greater mood episode severity also had worse relationships. Longitudinally, participants had largely stable relationships. To the extent that there were associations, changes in parental relationships may precede changes in episode severity, although the magnitude of this finding was small. Findings have implications for relationship interventions in BP youth