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Community pharmacies are well-positioned to improve the health of people with opioid use disorder and who use drugs by providing naloxone and other essential public health supplies. Respond to Prevent (R2P) is a clinical trial which sought to accelerate provision of harm reduction materials through a multicomponent intervention that included in-store materials, online training, and academic detailing. The objective of this study was to explore pharmacists' attitudes, knowledge, and experiences in providing naloxone, dispensing buprenorphine, and selling nonprescription syringes following participation in the R2P program. Two online asynchronous focus groups were conducted with community-based chain pharmacists across Massachusetts, New Hampshire, Oregon, and Washington who had participated in the R2P program. Participants accessed an online repository of group interview items and responded to questions over a short period. Each pharmacist participated anonymously for approximately 30 min over 2 ½ days. Pharmacists answered questions on experiences with pharmacy-based harm reduction care and R2P intervention implementation barriers and facilitators. Qualitative data analysis was conducted by a multidisciplinary team using an immersion-crystallization approach. A total of 32 pharmacists participated in the two focus groups. Most participants were female (n = 18, 56%), non-Hispanic (n = 29, 91%), and white (n = 17, 53%). Four major themes were identified related to (1) addressing bias and stigma toward people with opioid use disorder and who use drugs, (2) familiarity and comfort with naloxone provision, (3) perspective and practice shifts in nonprescription syringe sales, (4) structural challenges to harm reduction care in the pharmacy. Community pharmacists across the four states identified attitudes, knowledge, and experiences that create barriers to providing care to people with opioid use disorder and who use drugs. R2P approaches and tools were effective at reducing stigma and changing attitudes but were less effective at addressing structural challenges from the pharmacists' perspective. • Pharmacies are well-positioned to provide harm reduction services. • Education can address stigma and attitudinal barriers to harm reduction care. • Efforts to address system barriers to naloxone are needed. [ABSTRACT FROM AUTHOR]

As rates of overdoses involving opioids continue to rise in the United States, community pharmacies are uniquely positioned as a central access point of care for individuals to access harm reduction supplies, such as naloxone and nonprescription syringes (NPS). This study aimed to identify the facilitators and barriers of obtaining naloxone and NPS at community pharmacies that participated in Respond to Prevent (R2P), a multicomponent intervention to increase dispensing rates of naloxone, buprenorphine, and NPS. Pharmacy customers were recruited to participate in semistructured qualitative interviews conducted immediately after they obtained, or attempted to obtain, naloxone and NPS (when applicable) from R2P-participating pharmacies. Thematic analysis was conducted on the transcribed interviews, and content coding was applied to ethnographic notes and text messages from participants. Of the 32 participants, most (n = 28, 88%) successfully obtained naloxone and most of those seeking NPS successfully (n = 14, 82%) purchased them as well. Participants reported positive overall experiences at the community pharmacies. Participants described using the intervention advertising materials, as designed, to facilitate the request for naloxone. Many participants shared that they felt respected by pharmacists and that they valued naloxone counseling sessions that were tailored to meet their needs and allowed space for them to ask questions. Barriers included experiences where the intervention did not address structural challenges that prohibited the purchase of naloxone and where certain types of staff lacked knowledge, treated participants poorly, or did not adequately provide expected naloxone counseling. Pharmacy customer experiences obtaining naloxone and NPS in R2P-participating pharmacies identify facilitators and barriers to access that may be used to reform implementation and future interventions. Barriers identified can help enhance strategies or inform policies to improve pharmacy-based harm reduction supply distribution not addressed through existing interventions. [ABSTRACT FROM AUTHOR]

To investigate depression at 12 months after traumatic brain injury (TBI) in older adults compared with younger adults. Prospective longitudinal cohort study of persons with medically documented mild, moderate, and severe TBI at 12 months postinjury. Eighteen participating Level 1 trauma centers in the United States. Participants with TBI (N=1505) and primary outcome data at 12-month follow-up. Not applicable. Patient Health Questionnaire-9 (PHQ-9). PHQ-9 total scores were significantly lower for older adults (age≥65y; M=3.2) compared with younger adults (age<65y; M=5.0; B =−1.63, P <.001), indicating fewer depressive symptoms in older adults. Age did not interact with education, sex, race/ethnicity, psychiatric history, substance use, or Glasgow Coma Scale severity to affect PHQ-9 scores. Of the 29% of older adults who endorsed symptoms consistent with depression, 14% were classified as minor depression and 15% as major depression. The odds of older adults falling in the major depression vs no depression group were significantly lower (decreased by 56%) compared with younger adults (odds ratio=0.44, P =.001). At 12 months post-TBI, older adults endorse lower depressive symptoms than their younger counterparts and are less likely to experience major depression; however, over one-fourth of older adults endorsed symptoms consistent with depression, warranting evaluation and treatment. [ABSTRACT FROM AUTHOR]

Bettinger, J. S., K. J. Friston. Conceptual Foundations of Physiological Regulation incorporating the Free Energy Principle & Self-Organized Criticality. NEUROSCI BIOBEHAV REV 23(x) 144-XXX, 2022. Since the late nineteen-nineties, the concept of homeostasis has been contextualized within a broader class of "allostatic" dynamics characterized by a wider-berth of causal factors including social, psychological and environmental entailments; the fundamental nature of integrated brain-body dynamics; plus the role of anticipatory, top-down constraints supplied by intrinsic regulatory models. Many of these evidentiary factors are integral in original descriptions of homeostasis; subsequently integrated; and/or cite more-general operating principles of self-organization. As a result, the concept of allostasis may be generalized to a larger category of variational systems in biology, engineering and physics in terms of advances in complex systems, statistical mechanics and dynamics involving heterogenous (hierarchical/heterarchical, modular) systems like brain-networks and the internal milieu. This paper offers a three-part treatment. 1) interpret "allostasis" to emphasize a variational and relational foundation of physiological stability; 2) adapt the role of allostasis as "stability through change" to include a "return to stability" and 3) reframe the model of homeostasis with a conceptual model of criticality that licenses the upgrade to variational dynamics. • Allostasis "allo" + "stasis" as "variational & relational stability" • Allostasis as "stability through change" return to stability (physiological resilience) • Regulatory physiological processing should also operate at/near critical phase transitions • Variational/relational stability of allostatic processing is associated with a Griffiths region • To minimize free energy is to self-organize internal states into a Griffiths regime [ABSTRACT FROM AUTHOR]

Details of research to assess the procedural and conceptual knowledge of children in counting, are presented.

Precision cancer medicine is based on the ability to predict the dependencies of a given tumor from its molecular makeup. These dependencies can be exploited with targeted, cytotoxic and/or immunity-inducing therapeutics. Ongoing efforts to perform genomic and cellular analyses on clinically annotated patient tumors are powerful, but bounded to existing therapies and focused cohorts. Here, we describe how living tumor material is increasingly being used in the generation of a systematic laboratory-based functional map of cancer dependencies (a 'Cancer Dependency Map'). In particular, we emphasize the important contributions of long-term cell models, emerging uses for short-term cell models and future potential for 'alpha cultures' that are mere hours or days from the cancer patient. Collecting research-grade cancer dependency data with each of these model formats could pave the way to ensure that the Map increasingly reflects all tumors. The integration of clinical genomics and preclinical functional genomics data should provide a powerful research platform to improve the accuracy of precision medicine predictions. [ABSTRACT FROM AUTHOR]

Lithium manganese spinel, LiMn 2 O 4 (LMO), is a well-established active material for batteries, in which charge is stored via a two-stage insertion of Li + that manifests with coupled current peaks or voltage plateaus under voltammetric or galvanostatic conditions, respectively. The charge–discharge kinetics for LMO are significantly enhanced when the oxide is expressed in a nanoscale form, for example as an ultrathin coating of nanocrystallites at the surfaces of a 3D carbon substrate, such as fiber paper–supported carbon nanofoams (CNFs). In addition to expressing well-defined “battery-like” Li + -insertion peaks between ∼0.6 and 1 V vs . Ag/AgCl when cycled in aqueous lithium sulfate, LMO@CNF electrodes exhibit a pseudocapacitance envelop at more negative potentials (∼0.2–0.6 V). The pseudocapacitive character of LMO@CNF is further verified when cycled in aqueous sodium sulfate, where a broad capacitance envelop dominates the voltammetric response over the entire potential range at a current density an order of magnitude greater than expected for double-layer capacitance. Thus, the LMO@CNF electrode provides a prime example where multiple distinct charge-storage mechanisms are expressed in a single material. Herein, we apply voltammetry and impedance-based methods to deconvolve the respective contributions of double-layer capacitance, surface-based pseudocapacitance, and battery-like Li + insertion. The use of power-law analysis provides a general assignment of transport dynamics, while projecting impedance data as 3D Bode-style representations provides key mechanistic information regarding the time/frequency–potential response of LMO@CNF electrodes. [ABSTRACT FROM AUTHOR]

Printing high-resolution microwave passive devices directly on textile surfaces presents many challenges due to the high surface roughness and porosity of textile materials. This paper explains in detail physical and electromagnetic characterization of screen-printed coplanar waveguides (CPWs) on nonwoven textiles with a surface roughness of approximately ∼18 μm. Three different screen mesh counts (mesh opening unit) are used to screen print CPWs with five different resolutions. A screen printable silver paste is used as a conductive ink during the screen printing process. The difference in screen mesh counts affects the line resolution, thickness, conformity, and overall power transferring capacity of printed CPWs. A print resolution of 220 μm as the gap between the parallel lines of CPWs is achieved in this work without any surface modification of textile media. The surface roughness of the printed silver track is very similar to the base fabric (18 μm) when the screen with 305 mesh-count is selected for printing. Additionally, the thickness of the ink on the fabric is most conformal and lowest (23.4 μm) for the similar selection of screen mesh count. Fabricated CPWs are characterized for signals from 0.5 GHz to 10 GHz and compared to electromagnetic 3D simulation results. This paper also identifies minute printing faults in the 3D structure of the printed CPWs and correlates that with the scattering parameters of the transmission lines. Simulated and experimental data prove that a well-designed and process optimized printed nonwoven-based CPW works well (i.e. below 3 dB of insertion loss) for frequencies ranging from 0.5 GHz to 7 GHz. [ABSTRACT FROM AUTHOR]

For wild free-living animals the availability of food resources can be greatly affected by environmental perturbations such as weather events. In response to environmental perturbations, animals activate the hypothalamic-pituitary-adrenal (HPA) axis to adjust physiology and behavior. The literature asserts that during weather events food intake declines leading to changes in HPA axis activity, as measured by both baseline and stress-induced glucocorticoid concentrations. Here we investigated how body condition, locomotor activity, and stress physiology were affected by varying lengths of a fast (1, 2, 6, and 24 h; similar to that experienced by free-living birds) compared to when food was provided ad libitum in captive wintering male white-crowned sparrows, Zonotrichia leucophrys gambelii, exposed to a short day photoperiod. Baseline corticosterone concentrations were increased for all fasting durations but were highest in 6 and 24 h fasted birds. Stress-induced corticosterone was elevated in 1 h fasted birds with a trend for the 2 h of fast; no other differences were found. Baseline corticosterone concentrations were negatively related to both total fat scores and body mass. All birds lost body mass regardless of fast length but birds fasted for 24 h lost the most. Fat scores declined in the 6 and 24 h groups, and no measureable changes were detected in pectoralis muscle profile. Locomotor activity was increased over the entire period in which food was removed regardless of fasting duration. Together this suggests that reduced food availability is responsible, at least in part, for the rapid elevation both baseline corticosterone under any duration of fast and stress-induced concentrations during short-term fasts. [ABSTRACT FROM AUTHOR]

Neurons affected in Alzheimer’s disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy. Interventions that bolster mitochondrial health and/or stimulate mitophagy may therefore forestall the neurodegenerative process in AD. [ABSTRACT FROM AUTHOR]

Introduction: The timely administration of intravenous (IV) tissue plasminogen activator (t-PA) to acute ischemic stroke patients from the period of symptom presentation to treatment, door-to-needle (DTN) time, is an important focus for quality improvement and best clinical practice.Methods: A retrospective review of our Get With The Guidelines database was performed for a 5-hospital telestroke network for the period between January 2010 and January 2015. All acute ischemic stroke patients who were triaged in the emergency departments connected to the telestroke network and received IV t-PA were included. Optimal DTN time was defined as less than 60 minutes. Logistic regression was performed with clinical variables associated with DTN time. Age and National Institutes of Health Stroke Scale (NIHSS) score were categorized based on clinically significant cutoffs.Results: Six-hundred and fifty-two patients (51% women, 46% White, 45% Hispanic, and 8% Black) were included in this study. The mean age was 70 years (range 29-98). Of the variables analyzed, only arrival mode, initial NIHSS score, and the interaction between age and initial NIHSS score were significant. DTN time more than or equal to 60 minutes was most common in patients aged more than 80 years with NIHSS score higher than 10.Conclusions: The cause of DTN time delay for older patients with higher NIHSS score is unclear but was not related to presenting blood pressure or arrival mode. Further study of this subgroup is important to reduce overall DTN times. [ABSTRACT FROM AUTHOR]

Summary Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD + , and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD + reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD + also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. [ABSTRACT FROM AUTHOR]

Improvements in scientific instrumentation allow imaging at mesoscopic to atomic length scales, many spectroscopic modes, and now—with the rise of multimodal acquisition systems and the associated processing capability—the era of multidimensional, informationally dense data sets has arrived. Technical issues in these combinatorial scientific fields are exacerbated by computational challenges best summarized as a necessity for drastic improvement in the capability to transfer, store, and analyze large volumes of data. The Bellerophon Environment for Analysis of Materials (BEAM) platform provides material scientists the capability to directly leverage the integrated computational and analytical power of High Performance Computing (HPC) to perform scalable data analysis and simulation via an intuitive, cross-platform client user interface. This framework delivers authenticated, “push-button” execution of complex user workflows that deploy data analysis algorithms and computational simulations utilizing the converged compute-and-data infrastructure at Oak Ridge National Laboratory’s (ORNL) Compute and Data Environment for Science (CADES) and HPC environments like Titan at the Oak Ridge Leadership Computing Facility (OLCF). In this work we address the underlying HPC needs for characterization in the material science community, elaborate how BEAM’s design and infrastructure tackle those needs, and present a small sub-set of user cases where scientists utilized BEAM across a broad range of analytical techniques and analysis modes. [ABSTRACT FROM AUTHOR]

This research outlines six studies (total N = 3867) that develop and validate an Aggressive Beliefs and Attitudes — Short Form scale for use within the normal nonclinical adult population (e.g., organizational psychology). In the first two samples, exploratory factor analysis reduced the original 30 item scale to a shorter, more parsimonious, eight item measure. In the third sample, confirmatory factor analysis found that the proposed model and items fit the data extremely well. Examination of the nomological network underlying the new measure in Samples 3–4 displayed relationships with positive affect, negative affect, agreeableness, conscientiousness, and neuroticism ranging from r = .23 to − .23, while relationships with anger, hostility, physical aggression, and verbal aggression ranged from r = .49 to .30. Finally, in two criterion-related validity studies the relationships between the aggressive beliefs and attitudes scales, both original and short forms, and workplace deviance were examined with independent samples of employed adults. The short form scale was significantly related to workplace deviance in both samples ( r = .37 and .43). Furthermore, these relationships were of identical magnitude to the full 30 item measure, suggesting that the short form scale comparably captures aggression-related behaviors with a greatly reduced number of items. [ABSTRACT FROM AUTHOR]

As an obvious candidate for a p-type dopant in ZnO, nitrogen remains elusive in this role. Nitrogen containing precursors are a potential means to incorporate nitrogen during MOCVD growth. One class of nitrogen-containing precursors are zinc acetate amines, yet, they have received little attention. The synthesis and single crystal X-ray structure of [Zn(acetate) 2 (en)], and the synthesis of [Zn(acetate) 2 (en) 2 ], [Zn(acetate) 2 (benzylamine) 2 ], [Zn(acetate) 2 (butylamine) 2 ], [Zn(acetate) 2 (NH 3 ) 2 ], and [Zn(acetate) 2 (tris) 2 ], where en=ethylenediamine and tris=(tris[hydroxymethyl]aminomethane) are reported. The compounds were characterized by thermogravimetric analysis and pyrolyzed in air and inert gas to yield ZnO. These compounds are useful single source precursors to ZnO bulk powders by alkali precipitation and ZnO thin films by spray pyrolysis. The amine bound to the zinc influences the ZnO crystal size and shape and acts as a nitrogen donor for preparing nitrogen-doped ZnO during alkali precipitation. Thin films of ZnO prepared by spray pyrolysis using the precursors had a (100) preferred orientation and measured n-type to intrinsic conductivity. [ABSTRACT FROM AUTHOR]

Aims: Previously rare among Alaska Native (AN) people, type 2 diabetes (DM2) prevalence as indicated by registry data has increased by as much as 300% in some western Alaska regions. We sought to determine prevalence and incidence of DM2 and analyze associated cardiometabolic risk factors in western AN people.Methods: DM2 and prediabetes prevalence and incidence were determined by the Western Alaska Tribal Collaborative for Health using consolidated data from cohort studies conducted during 2000-2010. Crude and age-adjusted incidence for DM2 and prediabetes were calculated using 2010 American Diabetes Association criteria. Effects of covariates on DM2 and prediabetes were determined using univariate and multivariate Cox proportional hazards analyses, adjusted for age and sex.Results: Excluding baseline diabetes (n=124, 4.5%), 53 cases of new DM2 were identified among 2630 participants. Age- and sex-adjusted DM2 incidence was 4.3/1000 (95% CI 2.9, 5.0) person-years over an average 5.9-year follow up. After excluding baseline prediabetes, 387 new cases of prediabetes were identified among 1841 participants; adjusted prediabetes incidence was 44.5/1000 (95% CI 39.5, 49.5) person years. Independent predictors for DM2 included age, impaired fasting glucose, and metabolic syndrome; family history of diabetes and obesity were additional independent predictors for prediabetes.Conclusions: DM2 incidence in western AN people is substantially lower than that for U.S. whites; however, incidence of prediabetes is more than 10-fold higher than western AN DM2 incidence and more closely aligned with U.S. rates. Interventions aimed at achieving healthy lifestyles are needed to minimize risk factors and maximize protective factors for DM2 in this population. [ABSTRACT FROM AUTHOR]

Neurons in early visual cortex respond to both luminance- (1st order) and contrast-modulated (2nd order) local features in the visual field. In later extra-striate areas neurons with larger receptive fields integrate information across the visual field. For example, local luminance-defined features can be integrated into contours and shapes. Evidence for the global integration of features defined by contrast-modulation is less well established. While good performance in some shape tasks has been demonstrated with 2nd order stimuli, the integration of contours fails with 2nd order elements. Recently we developed a global orientation coherence task that is more basic than contour integration, bearing similarity to the well-established global motion coherence task. Similar to our previous 1st order result for this task, we find 2nd order coherence detection to be scale-invariant. There was a small but significant threshold elevation for 2nd order relative to 1st order. We used a noise masking approach to compare the efficiency of orientation integration for the 1st and 2nd order. We find a significant deficit for 2nd order detection at both the local and global level, however the small size of this effect stands in stark contrast against previous results from contour-integration experiments, which are almost impossible with 2nd order stimuli. [ABSTRACT FROM AUTHOR]