Behavior change interventions: the potential of ontologies for advancing science and practice

A central goal of behavioral medicine is the creation of evidence-based interventions for promoting behavior change. Scientific knowledge about behavior change could be more effectively accumulated using "ontologies." In information science, an ontology is a systematic method for articulating a "controlled vocabulary" of agreed-upon terms and their inter-relationships. It involves three core elements: (1) a controlled vocabulary specifying and defining existing classes; (2) specification of the inter-relationships between classes; and (3) codification in a computer-readable format to enable knowledge generation, organization, reuse, integration, and analysis. This paper introduces ontologies, provides a review of current efforts to create ontologies related to behavior change interventions and suggests future work. This paper was written by behavioral medicine and information science experts and was developed in partnership between the Society of Behavioral Medicine's Technology Special Interest Group (SIG) and the Theories and Techniques of Behavior Change Interventions SIG. In recent years significant progress has been made in the foundational work needed to develop ontologies of behavior change. Ontologies of behavior change could facilitate a transformation of behavioral science from a field in which data from different experiments are siloed into one in which data across experiments could be compared and/or integrated. This could facilitate new approaches to hypothesis generation and knowledge discovery in behavioral science

Rab-GTPase binding effector protein 2 (RABEP2) is a primed substrate for Glycogen Synthase kinase-3 (GSK3)

Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue. Rab-GTPase binding effector protein 2 (RABEP2) was identified as a novel GSK3 substrate and GSK3 phosphorylation of RABEP2 at Ser200 was enhanced by prior phosphorylation at Ser204, fitting the known consensus sequence for GSK3 substrates. Both residues are phosphorylated in cells while only Ser200 phosphorylation is reduced following inhibition of GSK3. RABEP2 function was originally identified as a Rab5 binding protein. We did not observe co-localisation of RABEP2 and Rab5 in cells, while ectopic expression of RABEP2 had no effect on endosomal recycling. The work presented identifies RABEP2 as a novel primed substrate of GSK3, and thus a potential biomarker for GSK3 activity, but understanding how phosphorylation regulates RABEP2 function requires more information on physiological roles of RABEP2

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score &gt;3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.</p

Deeply virtual and exclusive electroproduction of omega mesons

The exclusive omega electroproduction off the proton was studied in a large kinematical domain above the nucleon resonance region and for the highest possible photon virtuality (Q2) with the 5.75 GeV beam at CEBAF and the CLAS spectrometer. Cross sections were measured up to large values of the four-momentum transfer (-t < 2.7 GeV2) to the proton. The contributions of the interference terms sigma_TT and sigma_TL to the cross sections, as well as an analysis of the omega spin density matrix, indicate that helicity is not conserved in this process. The t-channel pi0 exchange, or more generally the exchange of the associated Regge trajectory, seems to dominate the reaction gamma* p -> omega p, even for Q2 as large as 5 GeV2. Contributions of handbag diagrams, related to Generalized Parton Distributions in the nucleon, are therefore difficult to extract for this process. Remarkably, the high-t behaviour of the cross sections is nearly Q2-independent, which may be interpreted as a coupling of the photon to a point-like object in this kinematical limit.Comment: 15 pages,19 figure

Q^2 Dependence of the S_{11}(1535) Photocoupling and Evidence for a P-wave resonance in eta electroproduction

New cross sections for the reaction $ep \to e'\eta p$ are reported for total center of mass energy $W$=1.5--2.3 GeV and invariant squared momentum transfer $Q^2$=0.13--3.3 GeV$^2$. This large kinematic range allows extraction of new information about response functions, photocouplings, and $\eta N$ coupling strengths of baryon resonances. A sharp structure is seen at $W\sim$ 1.7 GeV. The shape of the differential cross section is indicative of the presence of a $P$-wave resonance that persists to high $Q^2$. Improved values are derived for the photon coupling amplitude for the $S_{11}$(1535) resonance. The new data greatly expands the $Q^2$ range covered and an interpretation of all data with a consistent parameterization is provided.Comment: 31 pages, 9 figure

Measurement of Inclusive Spin Structure Functions of the Deuteron

We report the results of a new measurement of spin structure functions of the deuteron in the region of moderate momentum transfer ($Q^2$ = 0.27 -- 1.3 (GeV/c)$^2$) and final hadronic state mass in the nucleon resonance region ($W$ = 1.08 -- 2.0 GeV). We scattered a 2.5 GeV polarized continuous electron beam at Jefferson Lab off a dynamically polarized cryogenic solid state target ($^{15}$ND$_3$) and detected the scattered electrons with the CEBAF Large Acceptance Spectrometer (CLAS). From our data, we extract the longitudinal double spin asymmetry $A_{||}$ and the spin structure function $g_1^d$. Our data are generally in reasonable agreement with existing data from SLAC where they overlap, and they represent a substantial improvement in statistical precision. We compare our results with expectations for resonance asymmetries and extrapolated deep inelastic scaling results. Finally, we evaluate the first moment of the structure function $g_1^d$ and study its approach to both the deep inelastic limit at large $Q^2$ and to the Gerasimov-Drell-Hearn sum rule at the real photon limit ($Q^2 \to 0$). We find that the first moment varies rapidly in the $Q^2$ range of our experiment and crosses zero at $Q^2$ between 0.5 and 0.8 (GeV/c)$^2$, indicating the importance of the $\Delta$ resonance at these momentum transfers.Comment: 13 pages, 8 figures, ReVTeX 4, final version as accepted by Phys. Rev.

Search for Θ+(1540)\Theta^+(1540) pentaquark in high statistics measurement of γp→Kˉ0K+n\gamma p \to \bar K^0 K^+ n at CLAS

The exclusive reaction $\gamma p \to \bar K^0 K^+ n$ was studied in the photon energy range between 1.6-3.8 GeV searching for evidence of the exotic baryon $\Theta^+(1540)\to nK^+$. The decay to $nK^+$ requires the assignment of strangeness $S=+1$ to any observed resonance. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility corresponding to an integrated luminosity of 70 $pb^{-1}$. No evidence for the $\Theta^+$ pentaquark was found. Upper limits were set on the production cross section as function of center-of-mass angle and $nK^+$ mass. The 95% CL upper limit on the total cross section for a narrow resonance at 1540 MeV was found to be 0.8 nb.Comment: Submitted to Physical Review Letter

Measurement of the Polarized Structure Function σLT′\sigma_{LT^\prime} for p(e⃗,e′π+)np(\vec{e},e'\pi^+)n in the Δ(1232)\Delta(1232) Resonance Region

The polarized longitudinal-transverse structure function $\sigma_{LT^\prime}$ has been measured using the $p(\vec e,e'\pi^+)n$ reaction in the $\Delta(1232)$ resonance region at $Q^2=0.40$ and 0.65 GeV$^2$. No previous $\sigma_{LT^\prime}$ data exist for this reaction channel. The kinematically complete experiment was performed at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. A partial wave analysis of the data shows generally better agreement with recent phenomenological models of pion electroproduction compared to the previously measured $\pi^0 p$ channel. A fit to both $\pi^0 p$ and $\pi^+ n$ channels using a unitary isobar model suggests the unitarized Born terms provide a consistent description of the non-resonant background. The $t$-channel pion pole term is important in the $\pi^0 p$ channel through a rescattering correction, which could be model-dependent.Comment: 6 pages, LaTex, 5 eps figures: Submitted to PRC/Brief Reports v2: Updated referenc

Light Vector Mesons in the Nuclear Medium

The light vector mesons ($\rho$, $\omega$, and $\phi$) were produced in deuterium, carbon, titanium, and iron targets in a search for possible in-medium modifications to the properties of the $\rho$ meson at normal nuclear densities and zero temperature. The vector mesons were detected with the CEBAF Large Acceptance Spectrometer (CLAS) via their decays to $e^{+}e^{-}$. The rare leptonic decay was chosen to reduce final-state interactions. A combinatorial background was subtracted from the invariant mass spectra using a well-established event-mixing technique. The $\rho$ meson mass spectrum was extracted after the $\omega$ and $\phi$ signals were removed in a nearly model-independent way. Comparisons were made between the $\rho$ mass spectra from the heavy targets ($A > 2$) with the mass spectrum extracted from the deuterium target. With respect to the $\rho$-meson mass, we obtain a small shift compatible with zero. Also, we measure widths consistent with standard nuclear many-body effects such as collisional broadening and Fermi motion.Comment: 15 pages, 18 figures, 3 table

First measurement of coherent ϕ\phi-meson photoproduction on deuteron at low energies

The cross section and decay angular distributions for the coherent \phi meson photoproduction on the deuteron have been measured for the first time up to a squared four-momentum transfer t =(p_{\gamma}-p_{\phi})^2 =-2 GeV^2/c^2, using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The cross sections are compared with predictions from a re-scattering model. In a framework of vector meson dominance, the data are consistent with the total \phi-N cross section \sigma_{\phi N} at about 10 mb. If vector meson dominance is violated, a larger \sigma_{\phi N} is possible by introducing larger t-slope for the \phi N \to \phi N process than that for the \gamma N \to \phi N process. The decay angular distributions of the \phi are consistent with helicity conservation.Comment: 6 page