Choosing a physician depends on how you want to feel: The role of ideal affect in health-related decision making

When given a choice, how do people decide which physician to select? Although significant research has demonstrated that how people actually feel (their “actual affect”) influences their health care preferences, how people ideally want to feel (their “ideal affect”) may play an even greater role. Specifically, we predicted that people trust physicians whose affective characteristics match their ideal affect, which leads people to prefer those physicians more. Consistent with this prediction, the more participants wanted to feel high arousal positive states on average ([ideal HAP]; e.g., excited), the more likely they were to select a HAP-focused physician. Similarly, the more people wanted to feel low arousal positive states on average ([ideal LAP]; e.g., calm), the more likely they were to select a LAP-focused physician. Also as predicted, these links were mediated by perceived physician trustworthiness. Notably, while participants’ ideal affect predicted physician preference, actual affect (how much people actually felt HAP and LAP on average) did not. These findings suggest that people base even serious decisions on how they want to feel and highlight the importance of considering ideal affect in models of decision making, person perception, and patient physician communication

Healthcare worker competencies for disaster training

BACKGROUND: Although training and education have long been accepted as integral to disaster preparedness, many currently taught practices are neither evidence-based nor standardized. The need for effective evidence-based disaster training of healthcare staff at all levels, including the development of standards and guidelines for training in the multi-disciplinary health response to major events, has been designated by the disaster response community as a high priority. We describe the application of systematic evidence-based consensus building methods to derive educational competencies and objectives in criteria-based preparedness and response relevant to all hospital healthcare workers. METHODS: The conceptual development of cross-cutting competencies incorporated current evidence through a systematic consensus building process with the following steps: (1) review of peer-reviewed literature on relevant content areas and educational theory; (2) structured review of existing competencies, national level courses and published training objectives; (3) synthesis of new cross-cutting competencies; (4) expert panel review; (5) refinement of new competencies and; (6) development of testable terminal objectives for each competency using similar processes covering requisite knowledge, attitudes, and skills. RESULTS: Seven cross-cutting competencies were developed: (1) Recognize a potential critical event and implement initial actions; (2) Apply the principles of critical event management; (3) Demonstrate critical event safety principles; (4) Understand the institutional emergency operations plan; (5) Demonstrate effective critical event communications; (6) Understand the incident command system and your role in it; (7) Demonstrate the knowledge and skills needed to fulfill your role during a critical event. For each of the cross-cutting competencies, comprehensive terminal objectives are described. CONCLUSION: Cross-cutting competencies and objectives developed through a systematic evidence-based consensus building approach may serve as a foundation for future hospital healthcare worker training and education in disaster preparedness and response

Synergistic Induction of Apoptosis in Primary B-CLL Cells after Treatment with Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Histone Deacetylase Inhibitors

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently being investigated as a therapeutic agent for a variety of malignancies, as it triggers apoptosis specifically in transformed cells. However, TRAIL use as a stand alone therapeutic is hampered by the fact that many primary tumor cells are resistant to TRAIL-mediated apoptosis. Here, we investigated the extent to which pretreatment of TRAIL-resistant primary B-cell chronic lymphocytic leukemia (B-CLL) cells with histone deacetylase inhibitors (HDACis) could render them susceptible to killing by TRAIL. We found that HDAC inhibition in B-CLL cells led to increased TRAIL receptor expression, increased caspase activation, decreased expression of antiapoptotic regulators such as Bcl-2, and ultimately, enhanced TRAIL-induced apoptosis. Importantly, untransformed peripheral blood mononuclear cells remained largely resistant to TRAIL, even in the presence of HDACis. These results suggest that combination therapies using HDAC inhibition and TRAIL could prove beneficial for the treatment of B-CLL

Design, Synthesis and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse

Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse. We have recently reported that a mono-hydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies. In the current study, we show that systematic modification of an aminoalkylindole scaffold identified two new compounds with dual CB1R antagonist/CB2R agonist activity. Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration, without affecting total fluid intake and block the development of alcohol-conditioned place preference. Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse

Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity

K2 and several similar purported “incense products” spiked with synthetic cannabinoids are abused as cannabis substitutes. We hypothesized that metabolism of JWH-073, a prevalent cannabinoid found in K2, contributes to toxicity associated with K2 use. Competition receptor binding studies and G-protein activation assays, both performed by employing mouse brain homogenates, were used to determine the affinity and intrinsic activity, respectively, of potential monohydroxylated (M1, M3–M5) and monocarboxylated (M6) metabolites at cannabinoid 1 receptors (CB1Rs). Surprisingly, M1, M4 and M5 retain nanomolar affinity for CB1Rs, while M3 displays micromolar affinity and M6 does not bind to CB1Rs. JWH-073 displays equivalent efficacy to that of the CB1R full agonist CP-55,940, while M1, M3, and M5 act as CB1R partial agonists, and M4 shows little or no intrinsic activity. Further in vitro investigation by Schild analysis revealed that M4 acts as a competitive neutral CB1R antagonist (Kb~40nM). In agreement with in vitro studies, M4 also demonstrates CB1R antagonism in vivo by blunting cannabinoid-induced hypothermia in mice. Interestingly, M4 does not block agonist-mediated responses of other measures in the cannabinoid tetrad (e.g., locomotor suppression, catalepsy or analgesia). Finally, also as predicted by in vitro results, M1 exhibits agonist activity in vivo by inducing significant hypothermia and suppression of locomotor activity in mice. In conclusion, the present study indicates that further work examining the physiological effects of synthetic cannabinoid metabolism is warranted. Such a complex mix of metabolically produced CB1R ligands may contribute to the adverse effect profile of JWH-073-containing products

A Multi-State Model of the CaMKII Dodecamer Suggests a Role for Calmodulin in Maintenance of Autophosphorylation

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) accounts for up to 2 percent of all brain protein and is essential to memory function. CaMKII activity is known to regulate dynamic shifts in the size and signaling strength of neuronal connections, a process known as synaptic plasticity. Increasingly, computational models are used to explore synaptic plasticity and the mechanisms regulating CaMKII activity. Conventional modeling approaches may exclude biophysical detail due to the impractical number of state combinations that arise when explicitly monitoring the conformational changes, ligand binding, and phosphorylation events that occur on each of the CaMKII holoenzyme’s subunits. To manage the combinatorial explosion without necessitating bias or loss in biological accuracy, we use a specialized syntax in the software MCell to create a rule-based model of a twelve-subunit CaMKII holoenzyme. Here we validate the rule-based model against previous experimental measures of CaMKII activity and investigate molecular mechanisms of CaMKII regulation. Specifically, we explore how Ca²⁺/CaM-binding may both stabilize CaMKII subunit activation and regulate maintenance of CaMKII autophosphorylation. Noting that Ca²⁺/CaM and protein phosphatases bind CaMKII at nearby or overlapping sites, we compare model scenarios in which Ca²⁺/CaM and protein phosphatase do or do not structurally exclude each other’s binding to CaMKII. Our results suggest a functional mechanism for the so-called “CaM trapping” phenomenon, wherein Ca²⁺/CaM may structurally exclude phosphatase binding and thereby prolong CaMKII autophosphorylation. We conclude that structural protection of autophosphorylated CaMKII by Ca²⁺/CaM may be an important mechanism for regulation of synaptic plasticity

Costs of streamlined HIV care delivery in rural Ugandan and Kenyan clinics in the SEARCH Studys.

OBJECTIVES/DESIGN:As antiretroviral therapy (ART) rapidly expands in sub-Saharan Africa using new efficient care models, data on costs of these approaches are lacking. We examined costs of a streamlined HIV care delivery model within a large HIV test-and-treat study in Uganda and Kenya. METHODS:We calculated observed per-person-per-year (ppy) costs of streamlined care in 17 health facilities in SEARCH Study intervention communities (NCT: 01864603) via micro-costing techniques, time-and-motion studies, staff interviews, and administrative records. Cost categories included salaries, ART, viral load testing, recurring goods/services, and fixed capital/facility costs. We then modeled costs under three increasingly efficient scale-up scenarios: lowest-cost ART, centralized viral load testing, and governmental healthcare worker salaries. We assessed the relationship between community-specific ART delivery costs, retention in care, and viral suppression. RESULTS:Estimated streamlined HIV care delivery costs were $291/ppy. ART ($117/ppy for TDF/3TC/EFV [40%]) and viral load testing ($110/ppy for 2 tests/year [39$51/ppy), recurring costs ($5/ppy), and fixed costs ($7/ppy). Optimized ART scale-up with lowest-cost ART ($100/ppy), annual viral load testing ($24/ppy), and governmental healthcare salaries ($27/ppy), lowered streamlined care cost to$163/ppy. We found clinic-to-clinic heterogeneity in retention and viral suppression levels versus streamlined care delivery costs, but no correlation between cost and either retention or viral suppression. CONCLUSIONS:In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including viral load testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90-90-90 targets

The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 statement

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single-case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts.Funding for the SCRIBE project was provided by the Lifetime Care and Support Authority of New South Wales, Australia. The funding body was not involved in the conduct, interpretation or writing of this work. We acknowledge the contribution of the responders to the Delphi surveys, as well as administrative assistance provided by Kali Godbee and Donna Wakim at the SCRIBE consensus meeting. Lyndsey Nickels was funded by an Australian Research Council Future Fellowship (FT120100102) and Australian Research Council Centre of Excellence in Cognition and Its Disorders (CE110001021). For further discussion on this topic, please visit the Archives of Scientific Psychology online public forum at http://arcblog.apa.org. (Lifetime Care and Support Authority of New South Wales, Australia; FT120100102 - Australian Research Council Future Fellowship; CE110001021 - Australian Research Council Centre of Excellence in Cognition and Its Disorders)Published versio

Supernova Cosmology and the ESSENCE project

The proper usage of Type Ia supernovae (SNe Ia) as distance indicators has revolutionized cosmology, and added a new dominant component to the energy density of the Universe, dark energy. Following the discovery and confirmation era, the currently ongoing SNe Ia surveys aim to determine the properties of the dark energy. ESSENCE is a five year ground-based supernova survey aimed at finding and characterizing 200 SNe Ia in the redshift domain z=[0.2-0.8]. The goal of the project is to put constraints on the equation of state parameter, w, of the dark energy with an accuracy of <10%. This paper presents these ongoing efforts in the context of the current developments in observational cosmology.Comment: Submitted to EPS1