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Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
To assess the influence of mild behavioral impairment (MBI) on the cognitive performance of older adults who are cognitively healthy or have mild cognitive impairment (MCI).
Secondary data analysis of a sample (n = 497) of older adults from the Florida Alzheimer’s Disease Research Center who were either cognitively healthy (n = 285) or diagnosed with MCI (n = 212). Over half of the sample (n = 255) met the operationalized diagnostic criteria for MBI. Cognitive domains of executive function, attention, short-term memory, and episodic memory were assessed using a battery of neuropsychological tests.
Older adults with MBI performed worse on tasks of executive function, attention, and episodic memory compared to those without MBI. A significant interaction revealed that persons with MBI and MCI performed worse on tasks of episodic memory compared to individuals with only MCI, but no significant differences were found in performance in cognitively healthy older adults with or without MBI on this cognitive domain. As expected, cognitively healthy older adults performed better than individuals with MCI on every domain of cognition.
The present study found evidence that independent of cognitive status, individuals with MBI performed worse on tests of executive function, attention, and episodic memory than individuals without MBI. Additionally, those with MCI and MBI perform significantly worse on episodic memory tasks than individuals with only MCI. These results provide support for a unique cognitive phenotype associated with MBI and highlight the necessity for assessing both cognitive and behavioral symptoms.
We examine the performance of the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) persistent complex bereavement-related disorder (PCBD) criteria in bereaved adults to identify prolonged grief cases determined prospectively.
Bereaved adults (n = 138) were assessed at 8, 21, 32, 67, and 90 months after the sudden death of a spouse or close relative. We used latent class growth analysis to identify the longitudinal trajectories of grief assessed using the Inventory for Complicated Grief. To validate the trajectory that corresponded to prolonged grief, we examined the baseline predictors of these trajectories and their relationship with functional impairment.
We found three distinct trajectories of grief reactions. One of these trajectories (13.8%) showed high and sustained grief reactions that persisted for almost 7.5 years after the death. Participants with prolonged grief showed greater functional impairment [relative risk ratio (RRR) = 0.82, 95% confidence interval (CI): 0.70 to −0.97; p = 0.02] and higher self-reported depression (RRR = 1.21, 95% CI 1.09 to 1.96; p = 0.001) than participants whose grief reactions subsided over time. The original PCBD (requiring 6 criterion C symptoms) criteria correctly identified cases (57.9–94.7%) with perfect specificity (100%) but low to high sensitivity (5.6–81.3%); however, its sensitivity increased when revising criterion C to require ⩾3 (45.5–94.1%). The dimensional approach showed high sensitivity (0.50–1) and specificity (0.787–0.97).
We recommend revisions to the PCBD criteria, which are overly restrictive and may exclude cases with clinically significant grief-related distress and impairment. In the meantime, clinicians need to monitor grief symptoms over time using available dimensional approaches to reduce the burden of grief.
Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.
Microcrystal electron diffraction (MicroED) is a cryo-electron microscopy technique that utilizes three-dimensional nano- and microcrystals for high-resolution structure determination. These extremely small crystals are several orders of magnitude smaller than what is used in conventional x-ray diffraction experiments. MicroED is capable of providing high-quality data from samples that would otherwise be considered useless for diffraction measurements. Since its initial implementation, MicroED has been used in the fields of structural biology, chemistry, and materials science. In this article, we provide an overview of the MicroED methodology as well as examples of how MicroED in cryo-electron microscopy has been used for structure determination of a variety of samples.
Simulation plays an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High-quality, simulation-based research will ensure its effective use. This study sought to summarize simulation-based research activity and its facilitators and barriers, as well as establish priorities for simulation-based research in Canadian emergency medicine (EM).
Simulation-leads from Canadian departments or divisions of EM associated with a general FRCP-EM training program surveyed and documented active EM simulation-based research at their institutions and identified the perceived facilitators and barriers. Priorities for simulation-based research were generated by simulation-leads via a second survey; these were grouped into themes and finally endorsed by consensus during an in-person meeting of simulation leads. Priority themes were also reviewed by senior simulation educators.
Twenty simulation-leads representing all 14 invited institutions participated in the study between February and May, 2018. Sixty-two active, simulation-based research projects were identified (median per institution = 4.5, IQR 4), as well as six common facilitators and five barriers. Forty-nine priorities for simulation-based research were reported and summarized into eight themes: simulation in competency-based medical education, simulation for inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology.
This study summarized simulation-based research activity in EM in Canada, identified its perceived facilitators and barriers, and built national consensus on priority research themes. This represents the first step in the development of a simulation-based research agenda specific to Canadian EM.
Silphium spp. have garnered interest in Europe as a bioenergy crop and in North America as a perennial oilseed crop. However, very little has been done at this early stage of domestication to characterize wild collections for many key characteristics, including important oilseed traits. The objective of this work was to develop a basic understanding of how biogeography and associated population genetic forces have shaped seed phenotypes in plant collections across the native range of Silphium integrifolium Michx. (Asteraceae: Heliantheae), the primary domestication candidate for oilseed use. A collection of 53 accessions was grown in a common environment in Salina, KS, which is a location well within the native range of the species in central North America. Plants from each collection site were randomly mated by hand to produce seed representative of each accession, and the seeds subjected to seed dimensional trait, oil content and oil composition analyses. Kernel width varied along a latitudinal cline of collection site, while kernel length varied across a longitudinal cline. Palmitic and linoleic acids were inversely correlated with each other and varied along a longitudinal cline of the collection site. The results indicate that accessions collected from more southwesterly sites tended to have larger seed and those from more westerly sites had higher linoleic acid content and lower palmitic and myristic acids, which are all desirable phenotypes for an oilseed Silphium.
We study the metallicity calibrations in high-redshift galaxies using a sample of local analogs of high-redshift galaxies selected from the SDSS survey. Located in the same region on the BPT diagram as star-forming galaxies at z ∼ 2, these high-redshift analogs share the same ionized ISM conditions as high-redshift galaxies. We establish empirical metallicity calibrations between the direct gas-phase oxygen abundances and varieties of metallicity indicators in our local analogs using direct Te method. These new metallicity calibrations are the best means to measure the metallicity in high-redshift galaxies. There exist significant offsets between these new high-redshift metallicity calibrations and local calibrations. Such offsets are mainly driven by the evolution of the ionized ISM conditions from high-z to low-z.
Studies of domestic architectural variation are rare in archaeological research, possibly because the essential methods remain underdeveloped. To encourage a comparative approach to explaining the construction differences in household dwellings, we designed and utilized objective and easily applied means to calculate labor costs for constructing a variety of domestic architectural styles in Hohokam society. We applied Abrams's (1989, 1994) approach, labelled “architectural energetics,” which converts architecture into its labor equivalents for building structures. By doing so, we derived standard units of measurement that promote comparative analysis. To demonstrate the method's utility, we turned to the pithouses and adobe surface structures at Pueblo Grande. We wanted to test whether the history of construction was driven by environmental degradation, and, in particular, a depletion over time of wood resources for home building (see Loendorf and Lewis 2017). Our analysis indicated that factors in addition to wood depletion likely contributed to the architectural changes at Pueblo Grande and across the Hohokam world.
Tropical signalgrass (TSG) is one of the most problematic weeds found on golf courses, sports fields, and sod farms in south Florida. The recent ban of monosodium methane-arsonate (MSMA), an organic arsenical herbicide, from urban areas in Florida has left turfgrass managers searching for effective management options. In an effort to avoid relying solely on POST chemical control, this research examined the effect of combining a cultural practice, verticutting, along with PRE and POST herbicides as an integrated weed management approach to controlling TSG in hybrid bermudagrass. Field experiments were conducted at multiple locations over 2 yr in south Florida to: (1) determine whether verticutting before herbicide applications increases TSG control and (2) identify herbicide programs that effectively control TSG. No interactions between verticutting and herbicide programs were detected, but verticutting consistently provided a slight reduction (8% averaged across herbicide treatments) in TSG cover. Treatments containing a PRE herbicide resulted in a significant reduction (20% to 50%) in TSG cover at 52 wk after initial treatment (WAIT), while some POST herbicide treatments reduced TSG cover to <20% at 52 WAIT. A study was conducted to determine which POST herbicide combinations were most efficacious in controlling TSG. Amicarbazone alone provided ≤35% TSG control at 8 and 12 WAIT, but synergistic responses were observed between amicarbazone and mesotrione, trifloxysulfuron, and thiencarbazone+foramsulfuron+halosulfuron. Two- and three-way combinations of amicarbazone with these POST herbicides resulted in >80% TSG control at 4, 8, and 12 WAIT, with some reaching 100% TSG control at 4 WAIT. Based on these data, verticutting may provide limited complementary control, but certain combinations of POST herbicides exhibited excellent (>95%) TSG control.
In this paper, we explored various aspects of Canadian preservice elementary school teacher views about inclusive physical education. Based on prior work by Loreman (2014) that broadly examined preservice teacher views on inclusive education, in this study we looked specifically at inclusive physical education using a different sample of participants in the same program. Preservice teachers were asked a series of open-ended questions relating to their understandings, feelings of teaching self-efficacy, attitudes, and concerns relating to inclusive physical education in elementary school. Their responses reflected a strong focus on ability diversity (e.g., disability) and indicated that inclusive physical education means that all students should be part of the learning environment or that some should be excluded in roughly equal proportion. Depending on the curricular dimension, their self-perceived levels of preparedness ranged from low to high. The participants also presented a strong case for the necessity of resources available for the teaching of inclusive physical education.
In this paper, we summarise and critique a network meta-analysis (NMA) of antidepressant efficacy and tolerability for paediatric depression and an accompanying editorial. Although we agree that many of the extant studies are flawed, this meta-analysis showed clear efficacy of fluoxetine in the NMA, and for sertraline and escitalopram in pairwise analyses. Consequently, these papers underestimate the benefits of antidepressants for paediatric depression, and provide support for current practice guideline, which recommends the use of an antidepressant if the patient does not respond to psychotherapy. In these circumstances, fluoxetine should be the first choice, with escitalopram and sertraline as alternatives.
Declaration of interest
D.A.B. receives royalties from Guilford Press, has or will receive royalties from the electronic self-rated version of the C-SSRS from eResearch Technology, Inc., is on the editorial board of UpToDate, and is a reviewer for Healthwise. R.D.G. serves as an expert witness for the US Department of Justice, Pfizer, Wyeth and GSK; and is the founder of Adaptive Testing Technologies. P.W. receives personal fees from Lundbeck and Takeda. B.D. reports a licensing agreement with Lundbeck for a psychosocial treatment manual for depression. No other disclosures were reported.
While the growth of pits in passive metals exposed to chloride solutions is well understood, the processes associated with the initiation and propagation of stable pits, versus pits that form and apparently re-passivate, are still a matter of conjecture. A major challenge in studying pit initiation using electron microscopy has been alteration of the structure and chemistry of the hydrated corrosion films upon transfer to the vacuum environment of the microscope. A recently developed technique uses a microfluidic liquid cell to maintain the aqueous environment in contact with the sample. This work uses such cells to directly observe pits initiating, and growing before reaching stability, in aluminum thin films under potentiostatic polarization in situ in the electron microscope. Polarization curves developed in the cell show good agreement with those observed under conventional electrochemical experimental conditions. We observed current transients representative of metastable pitting and were able to relate crystalline features found in situ with topographic features using atomic force microscopy (AFM). An accumulation of aluminum surrounding an initiated pit, combined with depth profiling using Auger electron spectroscopy suggests that aluminum metal is deposited during the pit initiation process, and may serve to reduce lateral dissolution of the aluminum film. Work is currently underway to determine if this observation is unique to the geometry of the microfluidics cell or if is a general result that occurs at the very beginning of pit initiation.
UCDs are super massive star clusters found largely in dense regions but have also been found around individual galaxies and in smaller groups. Their origin is still under debate but consensus is that they formed either during major galaxy mergers as mergers of super massive star clusters, are simply the high mass end of the globular cluster luminosity function and formed in the same way as globular clusters, or that they formed from the threshing of galaxies and are remnant nuclear star clusters, which themselves may have formed from the mergers of globular star clusters within galaxies. We are attempting to disentangle these competing formation scenarios with a large survey of UCDs in the Coma cluster. Using ACS two-passband imaging from the HST/ACS Coma Cluster Treasury Survey, we are using colors and sizes to identify the UCD cluster members. With a large sample within the core region of the Coma cluster, we will use the population size, properties, and spatial distribution, and comparison with the Coma globular cluster and nuclear star cluster populations to discriminate between the threshing and globular cluster scenarios. In particular, previously we have found a possible correlation of UCD colors with host galaxy and a possible excess of UCDs around a non-central giant galaxy with an unusually large globular cluster population, both suggestive of a globular cluster origin. With a larger sample size, we are investigating whether the color correlation with host persists and whether the UCD population is consistent with, or in excess of, the bright end of the GCLF. We present initial results from the survey.
The extent to which observed differences in emotion processing and
regulation neural circuitry in adolescents with a history of suicide attempt
are paralleled by structural differences is unknown. We measured brain
cortical thickness and grey- and white-matter volumes in 100 adolescents: 28
with a history of suicide attempt and major depressive disorder (MDD); 31
with a history of MDD but no suicide attempt; and a healthy control group
(n = 41). The first group compared with controls showed
reduction in grey-matter volume in the right superior temporal gyrus (BA38),
a region important for social emotion processing.
Online educational resources (OERs) are increasingly available for emergency medicine (EM) education. This study describes and compares the use of free OERs by the Royal College of Physicians and Surgeons of Canada (RCPSC) EM residents and program directors (PDs) and investigates the relationship between the use of OERs and peer-reviewed literature.
A bilingual, online survey was distributed to RCPSC-EM residents and PDs using a modified Dillman method. The chi-square test and Fisher’s exact test were used to compare the responses of residents and PDs.
The survey was completed by 214/350 (61%) residents and 11/14 (79%) PDs. Free OERs were used by residents most frequently for general EM education (99.5%), procedural skills training (96%), and learning to interpret diagnostic tests (92%). OER modalities used most frequently included wikis (95%), file-sharing websites (95%), e-textbooks (94%), and podcasts (91%). Residents used wikis, podcasts, vodcasts, and file-sharing websites significantly more frequently than PDs. Relative to PDs, residents found entertainment value to be more important for choosing OERs (p<0.01). Some residents (23%) did not feel that literature references were important, whereas all PDs did. Both groups reported that OERs increased the amount of peer-reviewed literature (75% and 60%, respectively) that they read.
EM residents make extensive use of OERs and differ from their PDs in the importance that they place on their entertainment value and incorporation of peer-reviewed references. OERs may increase the use of peer-reviewed literature in both groups. Given the prevalence of OER use for core educational goals among RCPSC-EM trainees, future efforts to facilitate critical appraisal and appropriate resource selection are warranted.