Gamified cognitive control training for remitted depressed individuals : user requirements analysis

Background: The high incidence and relapse rates of major depressive disorder demand novel treatment options. Standard treatments (psychotherapy, medication) usually do not target cognitive control impairments, although these seem to play a crucial role in achieving stable remission. The urgent need for treatment combined with poor availability of adequate psychological interventions has instigated a shift toward internet interventions. Numerous computerized programs have been developed that can be presented online and offline. However, their uptake and adherence are oftentimes low. Objective: The aim of this study was to perform a user requirements analysis for an internet-based training targeting cognitive control. This training focuses on ameliorating cognitive control impairments, as these are still present during remission and can be a risk factor for relapse. To facilitate uptake of and adherence to this intervention, a qualitative user requirements analysis was conducted to map mandatory and desirable requirements. Methods: We conducted a user requirements analysis through a focus group with 5 remitted depressed individuals and individual interviews with 6 mental health care professionals. All qualitative data were transcribed and examined using a thematic analytic approach. Results: Results showed mandatory requirements for the remitted sample in terms of training configuration, technological and personal factors, and desirable requirements regarding knowledge and enjoyment. Furthermore, knowledge and therapeutic benefits were key requirements for therapists. Conclusions: The identified requirements provide useful information to be integrated in interventions targeting cognitive control in depression

Search for water in a super-Earth atmosphere: High-resolution optical spectroscopy of 55 Cancri e

We present the analysis of high-resolution optical spectra of four transits of 55Cnc e, a low-density, super-Earth that orbits a nearby Sun-like star in under 18 hours. The inferred bulk density of the planet implies a substantial envelope, which, according to mass-radius relationships, could be either a low-mass extended or a high-mass compact atmosphere. Our observations investigate the latter scenario, with water as the dominant species. We take advantage of the Doppler cross-correlation technique, high-spectral resolution and the large wavelength coverage of our observations to search for the signature of thousands of optical water absorption lines. Using our observations with HDS on the Subaru telescope and ESPaDOnS on the Canada-France-Hawaii Telescope, we are able to place a 3-sigma lower limit of 10 g/mol on the mean-molecular weight of 55Cnc e's water-rich (volume mixing ratio >10%), optically-thin atmosphere, which corresponds to an atmospheric scale-height of ~80 km. Our study marks the first high-spectral resolution search for water in a super-Earth atmosphere and demonstrates that it is possible to recover known water-vapour absorption signals, in a nearby super-Earth atmosphere, using high-resolution transit spectroscopy with current ground-based instruments.Comment: Accepted for publication in ApJ 12 pages, 9 figures. Email: [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

Mechanistic insights into allosteric regulation of the A2A adenosine G protein-coupled receptor by physiological cations.

Cations play key roles in regulating G-protein-coupled receptors (GPCRs), although their mechanisms are poorly understood. Here, 19F NMR is used to delineate the effects of cations on functional states of the adenosine A2A GPCR. While Na+ reinforces an inactive ensemble and a partial-agonist stabilized state, Ca2+ and Mg2+ shift the equilibrium toward active states. Positive allosteric effects of divalent cations are more pronounced with agonist and a G-protein-derived peptide. In cell membranes, divalent cations enhance both the affinity and fraction of the high affinity agonist-bound state. Molecular dynamics simulations suggest high concentrations of divalent cations bridge specific extracellular acidic residues, bringing TM5 and TM6 together at the extracellular surface and allosterically driving open the G-protein-binding cleft as shown by rigidity-transmission allostery theory. An understanding of cation allostery should enable the design of allosteric agents and enhance our understanding of GPCR regulation in the cellular milieu

Japanese Intentions for the Pearl Harbor Bombing

https://scholarworks.moreheadstate.edu/student_scholarship_posters/1024/thumbnail.jp

Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma

Immunotherapy; Prognostication; Metastatic renal cell carcinomaImmunoteràpia; Pronòstic; Carcinoma de cèl·lules renals metastàticInmunoterapia; Pronóstico; Carcinoma de células renales metastásicoBackground The combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC). Objective To establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria. Design, setting, and participants Patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups. Outcome measurements and statistical analysis Overall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were calculated using the Kaplan-Meier method and compared between IMDC risk groups within each treatment cohort by the log-rank test. The overall response rate (ORR) was calculated by physician assessment of the best overall response. The primary outcome was OS at 18 mo. Results and limitations In total, 728 patients received IPI-NIVO, 282 IO-VEGF, and 7163 VEGF-TT. The median follow-up times for patients remaining alive were 14.3 mo for IPI-NIVO, 14.9 mo IO-VEGF, and 34.4 mo for VEGF-TT. OS at 18 mo for favorable, intermediate, and poor risk was, respectively, 90%, 78%, and 50% for those receiving IPI-NIVO; 93%, 83%, and 74% for IO-VEGF; and 84%, 64%, and 28% for VEGF-TT. ORRs in favorable-, intermediate-, and poor-risk groups were 41.3%, 40.6%, and 33.0% for those receiving IPI-NIVO; 60.3%, 56.8%, and 40.9% for IO-VEGF; and 39.3%, 33.5%, and 20.9% for VEGF-TT, respectively. The IMDC model stratified patients into statistically distinct risk groups for the three endpoints of OS, TTNT, and TD within each treatment cohort. Limitations of this study were the retrospective design and short follow-up. Conclusions This study demonstrated that the IMDC model continues to risk stratify patients with mRCC treated with contemporary first-line IO combination therapies and provided real-world survival benchmarks

Tuning the dipole directed assembly of core-shell nickel coated gold nanorods

We present the dipole-directed assembly of nickel-coated gold nanorods into nanorings and nanowires. We used two different coating methods to synthesise these core-shell superstructures. Surprisingly, the two coating methods lead to very different kinds of dipole directed assembly. We show that the resultant dipole assembly is very sensitive to the reaction conditions and can be tuned to obtain core-shell nanochains, nanorings, and nanowires. In addition to the presented experimental work, cluster moving Monte Carlo simulations of a system of core-shell nanorods were carried out. These simulations are based on a small number of magnetic interaction energy terms and do not explicitly deal with steric interactions or van der Waals forces. The simulation results are in line with the obtained experimental results, confirming that the magnetic self-assembly of core-shell nanorods can be described by means of a relatively simple mode

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Purpose: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. Methods: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. Results: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be amore limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. Conclusions: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching

The origin of the Palaeoproterozoic AMCG complexes in the Ukrainian Shield : new U-Pb ages and Hf isotopes in zircon

This research gained financial support granted by the Royal Society, UK (2006/R4 IJP), and the Swedish Institute, Sweden. This paper is NORDSIM contribution number 484, and publication no. 62 of the Large Igneous Provinces – Supercontinent Reconstruction – Resource Exploration Project (CAMIRO Project 08E03, and NSERC CRDPJ 419503-11) (www.supercontinent.org, www.camiro.org/exploration/ongoing-projects), and a contribution to IGCP 648.The Ukrainian shield hosts two Palaeoproterozoic anorthosite-mangerite-charnockite-granite (AMCG) complexes (the Korosten and Korsun-Novomyrhorod complexes) that intruded Palaeoproterozoic continental crust in north-western and central parts of the shield, respectively. We report results of U-Pb zircon and baddeleyite dating of 16 samples from the Korosten plutonic complex (KPC), and 6 samples from the Korsun-Novomyrhorod plutonic complex (KNPC). Fifteen zircon samples from both complexes were also analysed for Hf isotopes. These new, together with previously published data indicate that the formation of the KPC started at c. 1815 Ma and continued until 1743 Ma with two main phases of magma emplacement at 1800-1780 and 1770-1758 Ma. Each of the main phases of magmatic activity included both basic and silicic members. The emplacement history of the KNPC is different from that of the KPC. The vast majority of the KNPC basic and silicic rocks were emplaced between c. 1757 and 1750 Ma; the youngest stages of the complex are represented by monzonites and syenites that were formed between 1748 and 1744 Ma. Both Ukrainian AMCG complexes are closely associated in space and time with mantle-derived mafic and ultramafic dykes. The Hf isotope ratios in the zircons indicate a predominantly crustal source for the initial melts with some input of juvenile Hf from mantle-derived tholeiite melts. The preferred model for the formation of the Ukrainian AMCG complexes involves the emplacement of large volumes of hot mantle-derived tholeiitic magma into the lower crust. This resulted in partial melting of mafic lower-crustal material, mixing of lower crustal and tholeiitic melts, and formation of ferromonzodioritic magmas. Further fractional crystallization of the ferromonzodioritic melts produced the spectrum of basic rocks in the AMCG complexes. Emplacement of the ferromonzodioritic and tholeiitic melts into the middle crust and their partial crystallization caused abundant melting of the ambient crust and formation of the large volumes of granitic rocks present in the complexes.PostprintPeer reviewe