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Objective Chronic pain has a significant impact on functioning and results in the disruption of one’s assumed life trajectory, potentially altering their self-perceived identity. The present research is designed to determine whether identity-related issues are associated with common chronic pain cognitions and pain-related disability, which may help inform understanding of clinical chronic pain populations. Method Ninety-eight adult chronic pain patients were assessed at a local pain clinic during a regularly scheduled appointment focusing on pain management. Multivariate hierarchal regression was used to determine whether issues related to identity and death anxiety were associated with pain catastrophizing, pain acceptance, and pain-related disability, above and beyond pain severity, fear-avoidance, and age. Results Self-concept clarity was significantly related to pain catastrophizing and pain acceptance, above and beyond death anxiety, pain severity, fear-avoidance, and age. Death anxiety was associated with pain catastrophizing, pain acceptance, and pain-related disability above and beyond pain severity, fear-avoidance, and age. Conclusions To the best of our knowledge, the present study is the first examination of self-concept clarity and death anxiety as they relate to pain catastrophizing, pain acceptance, and pain-related disability. These descriptive results support the inclusion of identity and death anxiety within the pain experience and could serve as a foundation for future directions relevant to clinical applications.

Widespread use of antimicrobials in human and veterinary medicine drives the emergence and dissemination of resistant bacteria in human, animal, and environmental reservoirs. The AVMA and FDA Center for Veterinary Medicine have both taken public positions emphasizing the importance of incorporating antimicrobial stewardship in veterinary clinical settings; however, a model for implementing a comprehensive antimicrobial stewardship program in veterinary practice is not readily available. In 2015, The Ohio State University College of Veterinary Medicine began developing a veterinary antimicrobial stewardship program modeled on existing programs in human health-care institutions and the 7 core elements of a successful hospital antimicrobial stewardship program, as defined by the CDC. The program includes comprehensive antimicrobial use guidelines, active environmental surveillance, and enhanced infection control procedures in The Ohio State University Veterinary Medical Center, along with routine monitoring and reporting of antimicrobial prescribing practices and antimicrobial susceptibility patterns of common pathogens isolated from patients and the hospital environment. Finally, programs have been developed to educate clinicians, staff, and students on antimicrobial resistance and appropriate antimicrobial prescribing practices. The antimicrobial stewardship program has been designed to help clinicians and students confidently make judicious antimicrobial use decisions and provide them with actionable steps that can help them act as strong stewards while providing the best care for their patients. This report describes our program and the process involved in developing it, with the intent that the program could serve as a potential model for other veterinary medical institutions.

Transition metals are thought to be among the most toxic components in atmospheric particulate matter (PM) due to their role in catalyzing reactive oxygen species (ROS) formation. We show that precipitation of the transition metals Fe(II), Fe(III), and Mn(II) are thermodynamically favored in phosphate-based assays used to measure the oxidative potential (OP) – a surrogate for toxicity – of PM. Fe and Mn precipitation is likely to occur at extremely low metal concentrations ( 100 μM) with visible precipitates provide quasi-validation of the thermodynamic modeling. Oxidation of Fe(II) to Fe(III) is likely to be rapid in all in vitro OP assays, transforming Fe to a much less soluble form. Fe precipitates are likely to increase the rate of precipitation of other metals and possibly induce co-precipitation. These results have direct relevance for all PO4-based assays; the implications for studies of PM toxicity are discussed.

Introduction Chronic pain and post-traumatic stress disorder (PTSD) comorbidity is prevalent among veterans and is associated with increased levels of pain severity and pain-related disability. An improved understanding of the relationship between these co-occurring disorders, in addition to effective integrated treatments, will develop by considering the changes to the PTSD diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The current study examined the relationship between the revised PTSD Checklist for DSM-5 (PCL-5) symptom clusters (i.e., intrusion, avoidance, negative alterations in cognition and mood [NACM], and arousal) and chronic pain measurements (i.e., pain severity, interference, and disability). Materials and Methods Participants included 103 veterans (ages 26-70, mean = 45.33) participating in a randomized clinical trial examining the efficacy of an interdisciplinary pain management program for chronic musculoskeletal pain. The study was approved by a university system Institutional Review Board and affiliated healthcare system. Results The participants with a provisional PTSD diagnosis based on PCL-5 responses (N = 76) had significantly greater pain severity, interference, and disability than the participants without a provisional diagnosis (N = 23). Correlations between symptom clusters and pain measurements were mostly significant and positive with varying strengths. The avoidance symptom cluster, however, had relatively weaker correlations with pain measurements and was not significantly associated with the numeric rating scale of pain severity. Path analyses revealed that, after controlling for avoidance symptoms, significant associations remained between NACM and all the pain measurements. After controlling for NACM symptoms, however, there were no significant associations between avoidance symptoms and pain measurements. Conclusion The current study highlights a need to re-examine the leading theories about the mutual maintenance of these disorders in order to develop effective integrative treatment approaches. PTSD-related avoidance may have a relatively weaker role in co-occurring chronic pain than the other symptom clusters and may have a qualitatively different role than chronic pain–related avoidance. Future research should explore the relationship between the avoidance in PTSD and the avoidance in chronic pain as well as identify which chronic pain measurements are the most useful when examining the relationship between PTSD and chronic pain. The potential impact of trauma-related cognition and mood on chronic pain indicates that this is an important area for intervention and should be considered in the development of integrated treatments for chronic pain and PTSD among veterans.

The substantial expansion of secure messaging (SM) via the patient portal in the last decade suggests that it is becoming a standard of care, but few have examined SM use longitudinally. We examined SM patterns among a diverse cohort of patients with diabetes (N = 19 921) and the providers they exchanged messages with within a large, integrated health system over 10 years (2006-2015), linking patient demographics to SM use. We found a 10-fold increase in messaging volume. There were dramatic increases overall and for patient subgroups, with a majority of patients (including patients with lower income or with self-reported limited health literacy) messaging by 2015. Although more physicians than nurses and other providers messaged throughout the study, the distribution of health professions using SM changed over time. Given this rapid increase in SM, deeper understanding of optimizing the value of patient and provider engagement, while managing workflow and training challenges, is crucial.

People often intentionally or unintentionally leave companion animals behind in an evacuation during a hazard event. In online animal rescue forums, people curate, comment on, and engage in posts d...

We assess risks posed by oak wilt—a disease caused by the fungal pathogen Bretziella fagacearum. Though not currently found in Canada, our distribution models indicate that suitable climate conditions currently occur in southern Ontario for B. fagacearum and two of its main insect dispersal vectors, Colopterus truncatus and Carpophilus sayi. Climate habitat for these species is projected to expand northward under climate change, with much of the oak range in eastern Canada becoming climatically suitable within the next two decades. Potential costs for the removal and replacement of oak street trees ranged from CDN$266 to $420 million, with variation related to uncertainty in costs, rate of tree replacement, and city-level estimates of oak street tree density. The value of standing oak timber in eastern Canada was estimated at CDN$126 million using provincial stumpage fees and as a CDN$24 million annual contribution to national Gross Domestic Product (GDP) when calculated using a combination of economic and forestry product statistics. These values can help inform the scale of eradication and/or management efforts in the event of future oak wilt introductions.

Local environments play influential roles in shaping individual and population-level outcomes. Yet, most literature and public health initiatives studying the built environment emphasize its role in environmental health or physical health but fail to consider its ability to influence social wellbeing. Rooted in a social determinant of health framework, this study investigates how a community’s social wellbeing is shaped by the built environment through exploring individuals’ social relationships and social interactions, specifically regarding experiences of social isolation, social loneliness, and social belonging, and the limitations or opportunities for such interactions and connections the environment imposes. Participants were selected from three geographic neighborhood tracts representing different combinations of median income, relative environment (rural versus urban) and access to available transportation and potential sites of social interaction. Collected participant data included social isolation and social loneliness scores, perceptions regarding community context and social belonging, and demographic factors (socio-structural factors). Through ANOVA and an OLS regression, our results suggest that while local built environments influence opportunities to encourage social wellbeing, socio-structural factors, such as marital status or income, can 1) overcome barriers related to physical access or 2) create additional barriers related to social access. Rather, the intersection of the community’s built environment and socio-structural factors interact to predict social isolation or social loneliness, influence perceptions related to objective accessibility, and is a potential determinant for social wellbeing, especially for socially disadvantaged individuals or households who are unable to access opportunities or spaces outside of their community.

The lack of reproducibility of animal experimental results between laboratories, particularly in studies investigating the microbiota, has raised concern among the scientific community. Factors such as environment, stress and sex have been identified as contributors, whereas dietary composition has received less attention. This study firstly evaluated the use of commercially available rodent diets across research institutions, with 28 different diets reported by 45 survey respondents. Secondly, highly variable ingredient, FODMAP (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) and gluten content was found between different commercially available rodent diets. Finally, 40 mice were randomized to four groups, each receiving a different commercially available rodent diet, and the dietary impact on cecal microbiota, short- and branched-chain fatty acid profiles was evaluated. The gut microbiota composition differed significantly between diets and sexes, with significantly different clusters in β-diversity. Total BCFA were highest (p = 0.01) and SCFA were lowest (p = 0.03) in mice fed a diet lower in FODMAPs and gluten. These results suggest that nutritional composition of commercially available rodent diets impact gut microbiota profiles and fermentation patterns, with major implications for the reproducibility of results across laboratories. However, further studies are required to elucidate the specific dietary factors driving these changes.

Monoclonal antibodies (mAbs) and vaccines have been proposed as medical countermeasures to treat opioid use disorder (OUD) and prevent opioid overdose. In contrast to current pharmacotherapies (e.g., methadone, buprenorphine, naltrexone, and naloxone) for OUD and overdose, which target brain opioid receptors, mAbs and vaccine-generated polyclonal antibodies sequester the target opioid in the serum and reduce drug distribution to the brain. Furthermore, mAbs offer several potential clinical benefits over approved medications, such as longer serum half-life, higher selectivity, reduced side effects, and no abuse liability. Using magnetic enrichment to isolate opioid-specific B cell lymphocytes prior to fusion with myeloma partners, this study identified a series of murine hybridoma cell lines expressing mAbs with high affinity for opioids of clinical interest, including oxycodone, heroin and its active metabolites, and fentanyl. In mice, passive immunization with lead mAbs against oxycodone, heroin, and fentanyl reduced drug-induced antinociception and the distribution of the target opioid to the brain. In mice and rats, mAb pretreatment reduced fentanyl-induced respiratory depression and bradycardia, two risk factors for opioid-related overdose fatality. Overall, these results support use of mAbs to counteract toxic effects of opioids and other chemical threats. SIGNIFICANCE STATEMENT: The incidence of fatal overdoses due to the widespread access to heroin, prescription opioids, and fentanyl suggests that current Food and Drug Administration–approved countermeasures are not sufficient to mitigate the opioid epidemic. Monoclonal antibodies (mAbs) may provide acute protection from overdose by binding to circulating opioids in serum. Use of mAbs prophylactically, or after exposure in combination with naloxone, may reduce hospitalization and increase survival.

Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has the potential to facilitate adherence and transform HIV prevention. However, little LAI PrEP research has occurred among women, who face unique barriers. We conducted 30 in-depth interviews with HIV-negative women from 2017-2018 across six sites (New York; Chicago; San Francisco; Atlanta; Washington, DC; Chapel Hill) of the Women's Interagency HIV Study. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Few women expressed interest in PrEP and when prompted to choose a regimen, 55% would prefer LAI, 10% daily pills, and 33% said they would not take PrEP regardless of formulation. Perceived barriers included: (1) the fear of new-and perceived untested-injectable products and (2) potential side effects (e.g., injection-site pain, nausea). Facilitators included: (1) believing shots were more effective than pills; (2) ease and convenience; and (3) confidentiality. Future studies should incorporate women's LAI PrEP-related experiences to facilitate uptake.

Background Posttraumatic headache is difficult to define and there is debate about the specificity of the 7-day headache onset criterion in the current definition. There is limited evidence available to guide decision making about this criterion. Method A nested cohort study of 193 treatment-seeking veterans who met criteria for persistent headache attributed to mild traumatic injury to the head, including some veterans with delayed headache onset up to 90 days post-injury, was undertaken. Survival analysis examined the proportion of participants reporting headache over time and differences in these proportions based on sex, headache phenotype, and mechanism of injury. Result 127 participants (66%; 95% CI: 59–72%) reported headache onset within 7 days of head injury and 65 (34%) reported headache onset between 8 days and 3 months after head injury. Fourteen percent of participants reported pre-existing migraine before head injury, and there was no difference in the proportion of veterans with pre-existing migraine based on headache onset. Headache onset times were not associated with sex, headache phenotype, or mechanism of injury. There were no significant differences in proportion of veterans with headache onset within 7 days of head injury based on headache phenotype (70% migraine onset within 7 days, 70% tension-type headache within 7 days, 56% cluster headache within 7 days; p ≥ .364). Similar findings were observed for head injury (64% blast, 60% blunt; p = .973). There were no significant differences observed between headache onset groups for psychiatric symptoms (Posttraumatic Stress Disorder Checklist for DSM-5 = 1.3, 95% CI = −27.5, 30.1; Patient Health Questionnaire-9 Item = 3.5, 95% CI = −6.3, 3.7; Generalized Anxiety Disorder Screener = 6.5, 95% CI = −2.7, 15.6). Conclusions Although most of the sample reported headache onset within 7 days of head injury, one-third experienced an onset outside of the diagnostic range. Additionally, veterans with headache onset within 7 days of head injury were not meaningfully different from those with later onset based on sex, headache phenotype, or mechanism of head injury. The ICHD-3 diagnostic criteria for 7-day headache onset should be expanded to 3 months. ClinicalTrials.gov Identifier NCT02419131

Background Chronic musculoskeletal pain is a complex problem, particularly for individuals with head injury and comorbid psychiatric conditions. The Fear Avoidance Model offers one of the strongest opportunities to conceptualize comorbid traumatic injury and pain, but this model is largely untested. Objective This study tests the Fear Avoidance Model of chronic pain using a sample from a study of polytrauma patients in a large Department of Veterans Affairs facility who participated in a federally-funded study of interdisciplinary chronic pain management. Methods The present study comprises a secondary analysis of 93 veterans with chronic pain, head injury, posttraumatic stress symptoms and a history of persistent opioid use. Standardized measures of Fear Avoidance Model risk factors (e.g., pain catastrophizing, fear avoidance beliefs, anxiety, depression) were examined as cross-sectional predictors of pain-related disability. Results Secondary data analysis revealed that Fear Avoidance Model factors accounted for almost 40% of the variance in pain-related disability, with pain catastrophizing and depression demonstrating the strongest relationships with disability. A summary variable combining all four factors revealed a 6% increase in disability for each factor that was clinically significant for the sample patients. Conclusions This study represents the first attempt to examine a complex, theoretical model of pain in a comorbid pain and TBI sample. Findings revealed a strong relationship between this model and pain-related disability that outperforms pain intensity ratings. This model could be used to guide better treatment for comorbid pain and TBI.

Chaikhot, D, Reed, K, Petroongrad, W, Athanasiou, F, van Kooten, D, and Hettinga, FJ. Effects of an upper-body training program involving resistance exercise and high-intensity arm cranking on peak handcycling performance and wheelchair propulsion efficiency in able-bodied men. J Strength Cond Res 34(8): 2267-2275, 2020-The aim of this study was to determine the training effects of an upper-body training program involving resistance exercise and high-intensity arm cranking on peak handcycling performance, propulsion efficiency, and biomechanical characteristics of wheelchair propulsion in able-bodied men. The training group (n = 10) received a 4-week upper-body resistance training (RT), 70% of 1 repetition maximum, 3 sets of 10 repetitions, 8 exercise stations, 2 times per week, combined with high-intensity interval training (HIIT) 2 times per week. High-intensity interval training consisted of arm-crank exercise, 7 intervals of 2 minutes at 80-90% of peak heart rate (HRpeak) with 2-minute active rest at 50-60% of HRpeak. The control group (n = 10) received no training. Both groups performed a preincremental and postincremental handcycling test until volitional exhaustion to evaluate fitness and a 4-minute submaximal wheelchair propulsion test at comfortable speed (CS), 125 and 145% of CS, to evaluate gross mechanical efficiency (GE), fraction of effective force (FEF), percentage of peak oxygen consumption (% V[Combining Dot Above]O2peak), and propulsion characteristics. Repeated-measures analysis of variance was performed (p < 0.05). Training resulted in a 28.2 ± 16.5% increase in peak power output, 13.3 ± 7.5% increase in V[Combining Dot Above]O2peak, 5.6 ± 0.9% increase in HRpeak, and 3.8 ± 1.5% decrease in HRrest. No training effects on FEF, GE, % V[Combining Dot Above]O2peak, and push characteristics were identified. In conclusion, the combined RT and arm-cranking HIIT improved fitness. However, it seems that this training did not result in improvements in propulsion efficiency and push characteristics. Additional wheelchair skill training may be needed to fully benefit from this advantage in daily life propulsion.

This study investigates how American English speakers from within and outside the Appalachian region interpret negative auxiliary inversion (NAI). Previously observed in Appalachian and other English varieties, NAI has surface syntax similar to yes-no questions but receives a declarative interpretation (e.g., Didn’t everybody watch Superbowl 53, meaning ‘not everybody watched’). Previous work shows that NAI is associated with a reading in which some but not all people participated in an event, as opposed to one in which no one participated. Results from an interpretation task revealed that Appalachian participants tended to obtain the ‘not all’ and not the ‘no one’ reading for NAI. In contrast, non-Appalachian participants’ interpretations exhibited greater inter- and intraspeaker variability. Appalachian participants with more ‘not all’ interpretations reported positive attitudes toward NAI use, and they also distinguished between attested and unattested syntactic subject types (e.g., everybody, many people, *few people) in a naturalness rating task. Appalachian participants with more ‘no one’ interpretations had more negative attitudes toward NAI use and made no distinction between subject types. These results highlight how individuals from Appalachia interpret NAI differently than individuals from outside the region and suggest that language attitudes may impact semantic interpretation within a nonmainstream speaker group.

Genetic screening to inform personal risk has only recently become an option as the cost of sequencing decreases, and our ability to interpret sequence variants improves. Studies have demonstrated that people want to learn about their genetic information and do well after learning it, but minorities are underrepresented in these studies. We surveyed Ashkenazi Jewish (AJ) and Latino/a participants in a genetic screening study to solicit choices about genetic results to return, as well as their experience with learning these results and attitudes about genetic information secrecy and security. Participants had the option to proceed through the study self-guided, and few elected to have traditional pre-test genetic education and counseling. Despite this, the majority were satisfied with the process of selecting and receiving genetic results and felt that they understood their results. Concerns about privacy and confidentiality of genetic data were minimal, though some participants expressed modest concerns about keeping any potential results secret or the confidentiality of their genetic information. Our results support the feasibility of the option of self-guided genetic screening. Additional care will need to be taken when designing population-based screening studies to meet the needs of participants who come from communities with different experiences with genetics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12687-020-00464-6) contains supplementary material, which is available to authorized users.

Objective: Research driven by terror management theory suggests sociocultural anxiety-buffer systems typically protect against existential anxiety, whereas anxiety buffer disruption theory suggests traumatic experiences may disrupt that process. Method: Following posttraumatic stress (PTS) symptom screening (n = 4097), individuals with low (n = 149) and high (n = 120) PTS engaged in either negative or positive self-evaluations, then reported death anxiety and appraised life's stressors as negative/threatening or positive/challenging. Results: When low PTS participants contemplated their worst (vs. best) selves, they experienced moderately heightened death anxiety yet appraised life's stressors as more positive/challenging than harmful/threatening, reflecting effective existential anxiety buffers. However, high PTS participants reported high death anxiety in both the best-self and worst-self conditions—indicating anxiety buffer disruption—and the worst-self (vs. best self) prompt increased their appraisal of life's stresses as a harmful threat and decreased appraisal as positive/challenging opportunities for growth and well-being. Discussion: Theoretical and clinical implications are discussed.

The relationship of a speaker’s language to their sense of place has been a focus of much of the sociolinguistic literature and dialect studies. However, the use of differing methodologies and measures makes comparison and contrast of the importance of place across different communities and social contexts problematic and drawing overarching conclusions challenging. To resolve this, the current article presents a way to quantitatively measure place-attachment using a Rootedness Metric that is both adaptable and comparable, permitting more nuanced understandings of place and language. Through three case studies, the author presents evidence that demonstrates the effectiveness of the Rootedness Metric to better understand how attachment to place impacts the phonetic variation in Appalachia. Inclusion of rootedness helps to explain why demographically similar speakers have divergent production, while the production of dissimilar speakers patterns alike.

Introduction: Syncope is common among emergency department (ED) patients with acute pulmonary embolism (PE) and indicates a higher acuity and worse prognosis than in patients without syncope. Whether presyncope carries the same prognostic implications has not been established. We compared incidence of intensive care unit (ICU) admission in three groups of ED PE patients: those with presyncope; syncope; and neither. Methods: This retrospective cohort study included all adults with acute, objectively confirmed PE in 21 community EDs from January 2013–April 2015. We combined electronic health record extraction with manual chart abstraction. We used chi-square test for univariate comparisons and performed multivariate analysis to evaluate associations between presyncope or syncope and ICU admission from the ED, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Among 2996 PE patients, 82 (2.7%) had presyncope and 109 (3.6%) had syncope. ICU admission was similar between groups (presyncope 18.3% vs syncope 25.7%) and different than their non-syncope counterparts (either 22.5% vs neither 4.7%; p

Schoenmakers, PPJM, Crisell, JJ, and Reed, KE. Physiological and perceptual demands of running on a curved nonmotorized treadmill compared with running on a motorized treadmill set at different grades. J Strength Cond Res 34(5): 1197-1200, 2020-The current study compared the physiological and perceptual demands of running on a commercially available curved nonmotorized treadmill (cNMT) with different incline grades on a motorized treadmill (MT). Ten male team-sport athletes completed, after a familiarization session, a 6-minute run at a target velocity of 2.78 m·s on the cNMT (cNMTrun). The mean individual running velocity of cNMTrun was then used as warm-up and experimental running velocity in 3 subsequent visits, in which subjects ran for 6 minutes on the MT set at different grades (4, 6, or 8%). In all experimental trials (cNMTrun, 4MTrun, 6MTrun, and 8MTrun) and in the warm-up of the subjects' third visit (1MTrun), oxygen consumption (V[Combining Dot Above]O2) and heart rate (HR) were monitored, and ratings of perceived exertion (RPE) were obtained. The HR in cNMTrun was significantly higher compared with all MT trials. V[Combining Dot Above]O2 and RPE were significantly higher in cNMTrun compared with 1MTrun and 4MTrun, but not different from 6MTrun and 8MTrun. The relationship between V[Combining Dot Above]O2 and MT grades was highly linear (V[Combining Dot Above]O2 = 34.36 + 1.7 MT grade; r = 0.99), and using linear interpolation, the concave curved design of the cNMT was estimated to mimic a 6.9 ± 3% MT grade. On matched running velocities, V[Combining Dot Above]O2 and RPE responses while running on the cNMT are similar to a 6-8% MT grade. These findings can be used as a reference value by athletes and coaches in the planning of cNMT training sessions and amend running velocities accordingly. Future studies are needed to determine whether this estimate is similar for female runners, or those of a lower body mass.

Breast cancers (BC) expressing estrogen and/or progesterone receptors, referred to as hormone receptor (HR)-positive represent the largest molecular subset of breast tumors. Fortunately, estrogen receptor expression on the cell surface serves as a drug target for endocrine therapy. In HR+, human epidermal growth factor receptor-2 (HER2) negative BC, neoadjuvant endocrine therapy (NET) is being increasingly used. While NET has been shown to reduce tumor cell proliferation causing apoptosis, up to 20% of tumors do not respond. Currently there are no validated predictive gene signatures distinguishing responders from non-responders to NET. Furthermore, there are limited data on the effects of different NET regimens in vivo and how they vary between responders and non-responders. Methods: We conducted a retrospective translational study in patients who were treated with NET at our institution. This study was approved by our institutional review board. Paired pre-treatment and surgical samples were collected from 24 patients along with clinico-pathological information. Responders were defined as those with a preoperative endocrine prognostic index (PEPI) score of 0. RNA isolation was performed using the Roche HighPure FFPET RNA Isolation spin-column kit. Purified RNA was hybridized with the PanCancer Code Set and finally the cartridge was scanned on the nCounter Digital Analyzer. Raw counts from each gene were imported into the nSolver Analysis. Log2 normalized data obtained from Nanostring nCounter analysis was analyzed for differentially expressed genes between pre- and post-treatment samples. The bioinformatics analysis was carried out using nCounter analysis software. Results: The median age at diagnosis was 64 years and NET used was anastrozole alone or in combination with fulvestrant. At baseline the majority of tumors were invasive ductal carcinomas (n=18), grade II (n=18), with a Ki67% >15% (n=16). Median duration of treatment with NET was 5 months (range 2-10 months). Nine tumors were defined as responders to NET and 15 were non-responders. In all of the 24 paired samples, we found 123 genes with a statistically significant change in expression (defined by greater than two-fold change and a false discovery rate adjusted p-value Conclusions: In our retrospective translational study we found that NET upregulates genes in the Jak-STAT, MAPK, RAS, cytosine-cytosine receptor interaction and PI3K-Akt signaling pathways and downregulates cell cycle pathway genes independent of type or duration of NET. We also found multiple genes involving the PI3K-Akt and Notch pathway were differentially expressed in pre-treatment specimens among responders compared to non-responders. While the sample size comparing responders versus non-responders was inadequate, our results suggest some early trends which warrant further investigation. Citation Format: Darien E Reed, Ritu Pandey, Jennifer M Segar, Michele Chu, Lauren LeBeau, Pavani Chalasani. Gene expression changes with neoadjuvant hormonal treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-05.

The degree of natal philopatry relative to natal dispersal in animal populations has important demographic and genetic consequences and often varies substantially within species. In salmonid fishes, lakes have been shown to have a strong influence on dispersal and gene flow within catchments; for example, populations spawning in inflow streams are often reproductively isolated and genetically distinct from those spawning in relatively distant outflow streams. Less is known, however, regarding the level of philopatry and genetic differentiation occurring at microgeographic scales, for example, where inflow and outflow streams are separated by very small expanses of lake habitat. Here, we investigated the interplay between genetic differentiation and fine‐scale spawning movements of brown trout between their lake‐feeding habitat and two spawning streams (one inflow, one outflow, separated by, We used a combination of PIT telemetry and genetic analyses to investigate the interplay between fine‐scale spawning movements and population structure of brown trout within a complex river system. Our research revealed evidence of distinctly asymmetrical, downstream‐biased dispersal patterns between inflow and outflow streams separated by less than 100 m of lake habitat. This asymmetry appears to facilitate the occurrence and maintenance of genetic structure at a microgeographic scale.

Understanding the climatic drivers of environmental variability (EV) during the Plio-Pleistocene and EV’s influence on mammalian macroevolution are two outstanding foci of research in African paleoclimatology and evolutionary biology. The potential effects of EV are especially relevant for testing the variability selection hypothesis, which predicts a positive relationship between EV and speciation and extinction rates in fossil mammals. Addressing these questions is stymied, however, by 1) a lack of multiple comparable EV records of sufficient temporal resolution and duration, and 2) the incompleteness of the mammalian fossil record. Here, we first compile a composite history of Pan-African EV spanning the Plio-Pleistocene, which allows us to explore which climatic variables influenced EV. We find that EV exhibits 1) a long-term trend of increasing variability since ∼3.7 Ma, coincident with rising variability in global ice volume and sea surface temperatures around Africa, and 2) a 400-ky frequency correlated with seasonal insolation variability. We then estimate speciation and extinction rates for fossil mammals from eastern Africa using a method that accounts for sampling variation. We find no statistically significant relationship between EV and estimated speciation or extinction rates across multiple spatial scales. These findings are inconsistent with the variability selection hypothesis as applied to macroevolutionary processes.

Transition metals in particulate matter (PM) are hypothesized to have enhanced toxicity based on their oxidative potential (OP). The acellular dithiothreitol (DTT) assay is widely used to measure the OP of PM and its chemical components. In our prior study, we showed that the DTT assay (pH 7.4, 0.1 M phosphate buffer, 37 °C) provides favorable thermodynamic conditions for precipitation of multiple metals present in PM. This study utilizes multiple techniques to characterize the precipitation of aqueous metals present at low concentrations in the DTT assay. Metal precipitation was identified using laser particle light scattering analysis, direct chemical measurement of aqueous metal removal, and microscopic imaging. Experiments were run with aqueous metals from individual metal salts and a well-characterized urban PM standard (NIST SRM-1648a, Urban Particulate Matter). Our results demonstrated rapid precipitation of metals in the DTT assay. Metal precipitation was independent of DTT but dependent on metal concentration. Metal removal in the chemically complex urban PM samples exceeded the thermodynamic predictions and removal seen in single metal salt experiments, suggesting co-precipitation and/or adsorption may have occurred. These results have broad implications for other acellular assays that study PM metals using phosphate buffer, and subsequently, the PM toxicity inferred from these assays.

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women’s perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women’s Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals.

Potable source-water reservoirs are the main water supplies in many urbanizing regions, yet their long-term responses to cultural eutrophication are poorly documented in comparison with natural lakes, creating major management uncertainties. Here, long-term discrete data (June 2006-June 2018) for classical eutrophication water quality indicators, continuous depth-profile data for dissolved oxygen (DO), and an enhanced hybrid statistical trend analysis model were used to evaluate the eutrophication status of a potable source-water reservoir. Based on classical indicators (nitrogen, N and phosphorus, P concentrations and ratios; phytoplankton biomass as chlorophyll a, chl a; and trophic state indices), the reservoir was eutrophic to hypereutrophic and stoichiometrically imbalanced. Anoxia/hypoxia occurred for 7-8 months annually systemwide, even throughout the water column for days to weeks in some years; and elevated total ammonia (up to ~900 μg tNH

OBJECTIVEHigh-deductible health plans (HDHPs) are increasingly more common but can be challenging for patients to navigate and may negatively affect care engagement for chronic conditions such as type 2 diabetes. We sought to understand how higher out-of-pocket costs affect participation in provider visits, medication adherence, and routine monitoring by patients with type 2 diabetes with an HDHP.RESEARCH DESIGN AND METHODSIn a retrospective cohort of 19,379 Kaiser Permanente Northern California patients with type 2 diabetes (age 18–64 years), 6,801 patients with an HDHP were compared with those with a no-deductible plan using propensity score matching. We evaluated the number of telephone and office visits with primary care, oral diabetic medication adherence, and rates of HbA1c testing, blood pressure monitoring, and retinopathy screening.RESULTSPatients with an HDHP had fewer primary care office visits compared with patients with no deductible (4.25 vs. 4.85 visits per person; P < 0.001), less retinopathy screening (49.9% vs. 53.3%; P < 0.001), and fewer A1c and blood pressure measurements (46.7% vs. 51.4%; P < 0.001 and 93.2% vs. 94.4%; P = 0.004, respectively) compared with the control group. Medication adherence was not significantly different between patients with an HDHP and those with no deductible (57.4% vs. 58.6%; P = 0.234).CONCLUSIONSHDHPs seem to be a barrier for patients with type 2 diabetes and reduce care participation in both visits with out-of-pocket costs and preventive care without out-of-pocket costs, possibly because of the increased complexity of cost sharing under an HDHP, potentially leading to decreased monitoring of important clinical measurements.

Increasing rates of infection and multidrug-resistant pathogens, along with a high use of antimicrobial therapy, make the intensive care unit (ICU) an ideal setting for implementing and supporting antimicrobial stewardship efforts. Overuse of antimicrobial agents is common in the ICU, as practitioners are challenged daily with achieving early, appropriate empiric antimicrobial therapy to improve patient outcomes. While early antimicrobial stewardship programs focused on the financial implications of antimicrobial overuse, current goals of stewardship programs align closely with those of critical care providers—to optimize patient outcomes, reduce development of resistance, and minimize adverse outcomes associated with antibiotic overuse and misuse such as acute kidney injury and Clostridioides difficile-associated disease. Significant opportunities exist in the ICU for critical care clinicians to support stewardship practices at the bedside, including thoughtful and restrained initiation of antimicrobial therapy, use of biomarkers in addition to rapid diagnostics, Staphylococcus aureus screening, and traditional microbiologic culture and susceptibilities to guide antibiotic de-escalation, and use of the shortest duration of therapy that is clinically appropriate. Integration of critical care practitioners into the initiatives of antimicrobial stewardship programs is key to their success. This review summarizes key components of antimicrobial stewardship programs and mechanisms for critical care practitioners to share the responsibility for antimicrobial stewardship.

A fundamental understanding of speech science is a critically important component in fields such as linguistics, communication disorders and sciences, cognitive science, and speech technology. Therefore, courses in speech communication are integral to the undergraduate and graduate curricula of these and other subjects. Despite being at the forefront of pedagogical innovations, speech science courses have lagged in representing cultural and linguistic diversity in the classroom. Many speech scientists understand that linguistic diversity is fundamental to human language systems. However, discussions of language variation tend to be relegated to a single section within a course. The lack of inclusion of diverse language varieties results in a lack of engagement with many social variables such as race, ethnicity, and gender identity, among others. We argue that this “status quo” in speech science courses must change, such that linguistic diversity must be addressed in and throughout all courses, even those where diversity is not the focus. We will present concerns with current approaches to teaching about cultural and linguistic diversity. Furthermore, we will explain the benefits of including diversity instruction throughout the curriculum. Finally, we present specific recommendations for instructors to incorporate teaching of linguistic diversity throughout their curriculum and speech science courses.