94 research outputs found

    Utilizing Principal Coach Reflections to Co-Develop an Effective Coaching Strategy in a Large Urban School District

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    Our Educational Leadership (EDL) program collaborated with a large urban district to provide coaching support for 15 principals. Principals were identified by their supervisor based on specific coaching needs. This collaboration allowed program faculty to design a coaching strategy. Utilization-focused program evaluation (Patton, 2008) was used to examine coaching practices that acknowledged the context, challenges and opportunities present in the district. Our interviews revealed the need for specific attention focusing on the first-hand experiences principals’ encounter in the field. The importance of relationship building and trust informed a consultee-centered approach. A cycle of inquiry allowed for collaboration and refinement of the process. Strategies implemented during the coaching process informed continuous improvement for our second year of coaching support

    Tidal effects on the radial velocity curve of HD77581 (Vela X-1)

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    The mass of the neutron star in Vela X-1 has been found to be more massive than the canonical 1.5 Mo. This result relies on the assumption that the amplitude of the optical component's measured radial velocity curve is not seriously affected by the interactions in the system. In this paper we explore the effect on the radial velocity curve caused by surface motions excited by tidal interactions. We use a calculation from first principles that involves solving the equations of motion of a Lagrangian grid of surface elements. The velocities on the visible surface of the star are projected along the line-of-sight to the observer to obtain the absorption-line profile in the observer's reference frame. The centroid of the line-profiles for different orbital phases is then measured and a simulated RV curve constructed. Models are run for the "standard" (vsini=116 km/s) and "slow" (56 km/s) supergiant rotation velocities. We find that the surface velocity field is complex and includes fast, small-spatial scale structures. It leads to strong variability in the photospheric line profiles which, in turn, causes significant deviations from a Keplerian RV curve. The peak-to-peak amplitudes of model RV curves are in all cases larger than the amplitude of the orbital motion. Keplerian fits to RV curves obtained with the "standard" rotation velocity imply a neutron star >1.7 Mo. However, a similar analysis of the "slow" rotational velocity models allows for m_ns ~ 1.5 Mo. Thus, the stellar rotation plays an important role in determining the characteristics of the perturbed RV curve. Given the observational uncertainty in GP Vel's projected rotation velocity and the strong perturbations seen in the published and the model RV curves, we are unable to rule out a small (~1.5 Mo) mass for the neutron star companion.Comment: 14 pages, 16 figures; A&A, accepte

    Identification of non‐reported bupropion metabolites in human plasma

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    Bupropion and its three active metabolites exhibit clinical efficacy in the treatment of major depression, seasonal depression and smoking cessation. The pharmacokinetics of bupropion in humans is highly variable. It is not known if there are any non‐reported metabolites formed in humans in addition to the three known active metabolites. This paper reports newly identified and non‐reported metabolites of bupropion in human plasma samples. Human subjects were dosed with a single oral dose of 75 mg of an immediate release bupropion HCl tablet. Plasma samples were collected and analysed by LC–MS/MS at 0, 6 and 24 h. Two non‐reported metabolites (M1 and M3) were identified with mass‐to‐charge (m/z) ratios of 276 (M1, hydration of bupropion) and 258 (M3, hydroxylation of threo/erythrohydrobupropion) from human plasma in addition to the known hydroxybupropion, threo/erythrohydrobupropion and the glucuronidation products of the major metabolites (M2 and M4–M7). These new metabolites may provide new insight and broaden the understanding of bupropion’s variability in clinical pharmacokinetics. © 2016 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134787/1/bdd2046_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134787/2/bdd2046.pd

    Ecologically valid long-term mood monitoring of individuals with bipolar disorder using speech

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    ABSTRACT Speech patterns are modulated by the emotional and neurophysiological state of the speaker. There exists a growing body of work that computationally examines this modulation in patients suffering from depression, autism, and post-traumatic stress disorder. However, the majority of the work in this area focuses on the analysis of structured speech collected in controlled environments. Here we expand on the existing literature by examining bipolar disorder (BP). BP is characterized by mood transitions, varying from a healthy euthymic state to states characterized by mania or depression. The speech patterns associated with these mood states provide a unique opportunity to study the modulations characteristic of mood variation. We describe methodology to collect unstructured speech continuously and unobtrusively via the recording of day-to-day cellular phone conversations. Our pilot investigation suggests that manic and depressive mood states can be recognized from this speech data, providing new insight into the feasibility of unobtrusive, unstructured, and continuous speech-based wellness monitoring for individuals with BP

    Fats and Factors: Lipid Profiles Associate with Personality Factors and Suicidal History in Bipolar Subjects

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    Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms

    The association between lithium use and neurocognitive performance in patients with bipolar disorder

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    Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.acceptedVersio

    Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions

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    <p>Abstract</p> <p>Background</p> <p>The combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. In a malaria model system, it has been shown that the progression of <it>Plasmodium berghei </it>through <it>Anopheles stephensi </it>and the survival of the mosquito both depend non-linearly on parasite density. These processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (TBIs) currently under development.</p> <p>Methods</p> <p>An individual-based stochastic mathematical model is used to investigate the combined impact of these multiple regulatory processes and examine how TBIs, which target different parasite life-stages within the mosquito, may influence overall parasite transmission.</p> <p>Results</p> <p>The best parasite molecular targets will vary between different epidemiological settings. Interventions that reduce ookinete density beneath a threshold level are likely to have auxiliary benefits, as transmission would be further reduced by density-dependent processes that restrict sporogonic development at low parasite densities. TBIs which reduce parasite density but fail to clear the parasite could cause a modest increase in transmission by increasing the number of infectious bites made by a mosquito during its lifetime whilst failing to sufficiently reduce its infectivity. Interventions with a higher variance in efficacy will therefore tend to cause a greater reduction in overall transmission than a TBI with a more uniform effectiveness. Care should be taken when interpreting these results as parasite intensity values in natural parasite-vector combinations of human malaria are likely to be significantly lower than those in this model system.</p> <p>Conclusions</p> <p>A greater understanding of the development of the malaria parasite within the mosquito is required to fully evaluate the impact of TBIs. If parasite-induced vector mortality influenced the population dynamics of <it>Plasmodium </it>species infecting humans in malaria endemic regions, it would be important to quantify the variability and duration of TBI efficacy to ensure that community benefits of control measures are not overestimated.</p

    Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

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    Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio

    Response to correspondence on Reproducibility of CRISPR-Cas9 Methods for Generation of Conditional Mouse Alleles: A Multi-Center Evaluation

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