Improving the external validity of clinical trials: the case of multiple chronic conditions

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built both through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.Journal of Comorbidity 2013;3(2)30–3

Confirming what we know: Understanding questionable research practices in intro physics labs

Many institutions are changing the focus of their introductory physics labs from verifying physics content towards teaching students about the skills and nature of science. As instruction shifts, so too will the ways students approach and behave in the labs. In this study, we evaluated students' lab notes from an early activity in an experimentation-focused lab course. We found that about 30% of student groups (out of 107 groups at three institutions) recorded questionable research practices in their lab notes, such as subjective interpretations of results or manipulating equipment and data. The large majority of these practices were associated with confirmatory goals, which we suspect stem from students' prior exposure to verification labs. We propose ways for experimentation-focused labs to better engage students in the responsible conduct of research and authentic scientific practice.Comment: 4 pages, 4 figure

Penetrating the Homunculus -- Near-Infrared Adaptive Optics Images of Eta Carinae

Near-infrared adaptive optics imaging with NICI and NaCO reveal what appears to be a three-winged or lobed pattern, the "butterfly nebula", outlined by bright Br$\gamma$ and H$_{2}$ emission and light scattered by dust. In contrast, the [Fe II] emission does not follow the outline of the wings, but shows an extended bipolar distribution which is tracing the Little Homunculus ejected in $\eta$ Car's second or lesser eruption in the 1890's. Proper motions measured from the combined NICI and NaCO images together with radial velocities show that the knots and filaments that define the bright rims of the butterfly were ejected at two different epochs corresponding approximately to the great eruption and the second eruption. Most of the material is spatially distributed 10\arcdeg to 20\arcdeg above and below the equatorial plane apparently behind the Little Homunculus and the larger SE lobe. The equatorial debris either has a wide opening angle or the clumps were ejected at different latitudes relative to the plane. The butterfly is not a coherent physical structure or equatorial torus but spatially separate clumps and filaments ejected at different times, and now 2000 to 4000 AU from the star.Comment: 42 pages, 12 figures, To appear in the Astronomical Journa

Perfectionistic Strivings are Neither Adaptive, Healthy, Positive, Functional, nor Advisable: Findings From Six Peer-Reviewed Journal Articles

This article-based dissertation incrementally advanced our understanding of the contentiously debated (mal)adaptiveness of perfectionistic strivings (i.e., self-oriented perfectionism and personal standards). Perfectionistic strivings’ relations with negative emotionality, narcissism, depressive symptoms, and suicide were examined using structural equation modeling, path analysis, and meta-analysis. Additionally, bifactor modeling was used to explore how controlling for perfectionistic concerns (i.e., socially prescribed perfectionism, concern over mistakes, and doubts about actions) impacts perfectionistic strivings’ factor structure. Results suggest perfectionistic strivings are neither adaptive, healthy, positive, functional, nor advisable. Indeed, perfectionistic strivings exacerbated perfectionistic concerns’ relationship with negative emotionality. Likewise, controlling for perfectionistic concerns rendered perfectionistic strivings an unreliable factor. Self-oriented perfectionism also had a small, unique positive relationship with narcissistic grandiosity. Furthermore, perfectionistic strivings predicted small longitudinal increases in depressive symptoms beyond neuroticism. Similarly, daughters’ self-oriented perfectionism conferred risk for daughters’ depressive symptoms by eroding daughters’ social self-esteem. Lastly, perfectionistic strivings had a small positive relationship with suicide ideation. Overall, findings lend credence and coherence to theoretical accounts suggesting self-imposed pressures to be perfect are part of the premorbid personality of people prone to depression, suicide, social disconnection, negative emotionality, and narcissistic grandiosity. Investigators are strongly advised to cease a-priori labeling perfectionistic strivings “adaptive perfectionism”; doing so is an oversimplification of a double-edged, potentially lethal, construct. Researchers are also encouraged to explore further the perils of partialling

The Perfectionism-Psychological Outcome Link: The Mediating Effect of Personal Resiliency

Perfectionism is a multidimensional personality trait encompassing two higher-order dimensions: perfectionistic strivings and perfectionistic concerns. People high in perfectionistic strivings rigidly and ceaselessly demand perfection of the self and hold unrealistically high personal standards. People high in perfectionistic concerns have overly negative reactions to perceived failures, nagging self-doubts, and excessive concerns over other’s expectations. Research suggests perfectionistic strivings are predominantly associated with positive psychological outcomes, whereas perfectionistic concerns are predominantly associated with negative psychological outcomes. Theory suggests differences in personal resiliency may account for the divergent psychological outcomes associated with perfectionistic strivings and perfectionistic concerns. However, this contention has yet to be tested. It is currently unclear which perfectionism dimensions, if any, are uniquely associated with personal resiliency. The present study addresses this gap in knowledge. Perfectionistic strivings and perfectionistic concerns were hypothesized to correlate significantly with personal resiliency. In addition, personal resiliency was hypothesized to mediate the link between perfectionism dimensions and psychological outcomes. A sample of 425 undergraduates completed measures of perfectionistic strivings, perfectionistic concerns, personal resiliency, negative emotionality, positive affect, negative affect, life satisfaction, and coping strategies. All hypotheses were supported. Personal resiliency appears to mediate the relationship between perfectionism dimensions and both positive and negative psychological outcomes

Accurate polarization within a unified Wannier function formalism

We present an alternative formalism for calculating the maximally localized Wannier functions in crystalline solids, obtaining an expression which is extremely simple and general. In particular, our scheme is exactly invariant under Brillouin zone folding, and therefore it extends trivially to the Gamma-point case. We study the convergence properties of the Wannier functions, their quadratic spread and centers as obtained by our simplified technique. We show how this convergence can be drastically improved by a simple and inexpensive ``refinement'' step, which allows for very efficient and accurate calculations of the polarization in zero external field.Comment: 9 pages, 4 figure

Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.https://scholarscompass.vcu.edu/gradposters/1078/thumbnail.jp

A Dense Gas Trigger for OH Megamasers

HCN and CO line diagnostics provide new insight into the OH megamaser (OHM) phenomenon, suggesting a dense gas trigger for OHMs. We identify three physical properties that differentiate OHM hosts from other starburst galaxies: (1) OHMs have the highest mean molecular gas densities among starburst galaxies; nearly all OHM hosts have = 10^3-10^4 cm^-3 (OH line-emitting clouds likely have n(H2) > 10^4 cm^-3). (2) OHM hosts are a distinct population in the nonlinear part of the IR-CO relation. (3) OHM hosts have exceptionally high dense molecular gas fractions, L(HCN)/L(CO)>0.07, and comprise roughly half of this unusual population. OH absorbers and kilomasers generally follow the linear IR-CO relation and are uniformly distributed in dense gas fraction and L(HCN), demonstrating that OHMs are independent of OH abundance. The fraction of non-OHMs with high mean densities and high dense gas fractions constrains beaming to be a minor effect: OHM emission solid angle must exceed 2 pi steradians. Contrary to conventional wisdom, IR luminosity does not dictate OHM formation; both star formation and OHM activity are consequences of tidal density enhancements accompanying galaxy interactions. The OHM fraction in starbursts is likely due to the fraction of mergers experiencing a temporal spike in tidally driven density enhancement. OHMs are thus signposts marking the most intense, compact, and unusual modes of star formation in the local universe. Future high redshift OHM surveys can now be interpreted in a star formation and galaxy evolution context, indicating both the merging rate of galaxies and the burst contribution to star formation.Comment: 5 pages, 3 figures, 1 table, accepted by ApJ Letter

Staircase to Higher-Order Topological Phase Transitions

We find a series of topological phase transitions of increasing order, beyond the more standard second-order phase transition in a one-dimensional topological superconductor. The jumps in the order of the transitions depend on the range of the pairing interaction, which is parametrized by an algebraic decay with exponent $\alpha$. Remarkably, in the limit $\alpha = 1$ the order of the topological transition becomes infinite. We compute the critical exponents for the series of higher-order transitions in exact form and find that they fulfill the hyperscaling relation. We also study the critical behaviour at the boundary of the system and discuss potential experimental platforms of magnetic atoms in superconductors.Comment: 5+5pages, 7 figures. Accepted as a Rapid Communicatio

Enhancing research quality and reporting: why the Journal of Comorbidity is now publishing study protocols

The Journal of Comorbidity was launched in 2011 and has since become established as a high-quality journal that publishes open-access, peer-reviewed articles, with a focus on advancing the clinical management of patients with comorbidity/multimorbidity. To further enhance research quality and reporting of studies in this field, the journal is now offering authors the opportunity to publish a summary of their study protocols – a move designed to generate interest and raise awareness in ongoing clinical research and to enable researchers to detail their methodologies in order that replication by scientific peers is possible