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Abstract Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer’s disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

Abstract Background Heart failure (HF) is a debilitating disease with worsening symptoms and family caregiving burden. HF affects more than 8 million Americans. West Virginia has the highest HF death rate in the U.S. and limited healthcare services. This study tested whether the family HF palliative and end-of-life care intervention (FamPALcare) improved patient and caregiver outcomes at 3- and 6-month study endpoints. Methods This study used a randomized controlled trial design. Patients with HF and their caregivers were randomly assigned together to the intervention (n = 21) or control (n = 18) group. The intervention included five telephone coaching sessions on the HF home, palliative, and end-of-life care. The outcome data collected at baseline and at 3 and 6 months were from the patients’ (a) HF-related health status and depression/anxiety scale scores; and from caregivers’ (b) caregiving burden and depression/anxiety scale scores; and (c) anonymous ratings on the 11-item FamPALcare helpfulness scale, completed by the intervention participants. Results The mean age of the patients was 65.66 (SD = 13.72) years, and 67% were White males. The mean age of the caregivers was 62.05 (SD = 13.14) years, and 77% were White females. Compared to the controls, patients in the intervention group had significantly greater scores for HF-related health status (p

Background: A social justice framework can be used to inform healthy equity-focused research, and operationalizing social justice can inform strategic planning for research and practice models. This study aimed to develop a working definition of social justice based on input from a diverse group of collaborators to better inform the work conducted within the Center for Research, Health, and Social Justice. Methods: A concept mapping study was conducted from March to May 2022. A prompt designed to elicit social justice themes was developed (phase 1). At a study website, participants brainstormed statements that represented their definition of social justice (phase 2). Participants then sorted statements based on similarity and rated statements on importance (phase 3). Multidimensional scaling and hierarchical cluster analysis were used to identify nonoverlapping thematic clusters of statements (phase 4). Models were reviewed for best fit, and clusters were assigned names based on theme (phase 5). Results: Participants (n = 49) generated 52 unique statements that were sorted into 5 clusters describing social justice themes. Clusters included (1) Empathy, Awareness, and Understanding (n = 11); (2) Education and Systems Change (n = 10); (3) Policy Design and Implementation (n = 9); (4) Equity and Leveling the Playing Field (n = 11); and (5) Access to Services and Fair Living Standard (n = 11). High mean cluster ratings ranging from 5.22 to 6.02 out of 7 indicated all clusters were rated as being very important aspects of social justice. Conclusions: These data can guide the restructuring of research ecosystems that help eliminate race- and place-based health disparities.

Abstract Background Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations. Methods We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61–73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter. Results After adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals. Conclusions These results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

Background Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. Methods We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. Results Providers believed earlier initiation would signal an “extra sense of urgency” about the importance of antiretroviral therapy—a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. Conclusion Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.

In September 2023 the United States Food and Drug Administration (FDA) released draft guidance for comment about how informed client consent for companion animal clinical trials should be obtained. This guidance has the potential to substantially change how informed consent documents are written and presented to clients in the veterinary community. It provides specifics not only about how to obtain informed consent from owners but also the timeframe within which consent should be obtained, the formatting and language in the consent forms, and details on elements that are required to be in these consent forms. These changes will involve additional efforts by investigators to ensure compliance yet might lead to increased owner compliance and higher enrollment in clinical studies with subsequent benefits for all.

BackgroundWhile the advantages of using the internet and social media for research recruitment are well documented, the evolving online environment also enhances motivations for misrepresentation to receive incentives or to “troll” research studies. Such fraudulent assaults can compromise data integrity, with substantial losses in project time; money; and especially for vulnerable populations, research trust. With the rapid advent of new technology and ever-evolving social media platforms, it has become easier for misrepresentation to occur within online data collection. This perpetuation can occur by bots or individuals with malintent, but careful planning can help aid in filtering out fraudulent data. ObjectiveUsing an example with urban American Indian and Alaska Native young women, this paper aims to describe PRIOR (Protocol for Increasing Data Integrity in Online Research), which is a 2-step integration protocol for combating fraudulent participation in online survey research. MethodsFrom February 2019 to August 2020, we recruited participants for formative research preparatory to an online randomized control trial of a preconceptual health program. First, we described our initial protocol for preventing fraudulent participation, which proved to be unsuccessful. Then, we described modifications we made in May 2020 to improve the protocol performance and the creation of PRIOR. Changes included transferring data collection platforms, collecting embedded geospatial variables, enabling timing features within the screening survey, creating URL links for each method or platform of data collection, and manually confirming potentially eligible participants’ identifying information. ResultsBefore the implementation of PRIOR, the project experienced substantial fraudulent attempts at study enrollment, with less than 1% (n=6) of 1300 screened participants being identified as truly eligible. With the modified protocol, of the 461 individuals who completed a screening survey, 381 did not meet the eligibility criteria assessed on the survey. Of the 80 that did, 25 (31%) were identified as ineligible via PRIOR. A total of 55 (69%) were identified as eligible and verified in the protocol and were enrolled in the formative study. ConclusionsFraudulent surveys compromise study integrity, validity of the data, and trust among participant populations. They also deplete scarce research resources including respondent compensation and personnel time. Our approach of PRIOR to prevent online misrepresentation in data was successful. This paper reviews key elements regarding fraudulent data participation in online research and demonstrates why enhanced protocols to prevent fraudulent data collection are crucial for building trust with vulnerable populations. Trial RegistrationClinicalTrials.gov NCT04376346; https://www.clinicaltrials.gov/study/NCT04376346 International Registered Report Identifier (IRRID)DERR1-10.2196/52281

Abstract Staphylococcus pseudintermedius is historically understood as a prevalent commensal and pathogen of dogs, though modern clinical diagnostics reveal an expanded host-range that includes humans. It remains unclear whether differentiation across S. pseudintermedius populations is driven primarily by niche-type or host-species. We sequenced 501 diagnostic and commensal isolates from a hospital, veterinary diagnostic laboratory, and within households in the American Midwest, and performed a comparative genomics investigation contrasting human diagnostic, animal diagnostic, human colonizing, pet colonizing, and household-surface S. pseudintermedius isolates. Though indistinguishable by core and accessory gene architecture, diagnostic isolates harbor more encoded and phenotypic resistance, whereas colonizing and surface isolates harbor similar CRISPR defense systems likely reflective of common household phage exposures. Furthermore, household isolates that persist through anti-staphylococcal decolonization report elevated rates of base-changing mutations in – and parallel evolution of – defense genes, as well as reductions in oxacillin and trimethoprim-sulfamethoxazole susceptibility. Together we report parallel niche-specific bolstering of S. pseudintermedius defense mechanisms through gene acquisition or mutation.

Abstract Background The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. Objectives To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non‐PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. Animals Thirty‐one client‐owned dogs with CE: 23 non‐PLE, 8 PLE. Methods Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long‐term follow‐up at 26 weeks. Concurrent medications were allowed in PLE. Results Nineteen of 23 (83%; 95% confidence interval [CI], 60%‐94%) non‐PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%‐100%) at 26 weeks. Serum cobalamin concentration was increased (P

Abstract Introduction The Oncotype Dx Genomic Prostate Score (GPS) is a 17‐gene relative expression assay that predicts adverse pathology at prostatectomy. We conducted a novel randomized controlled trial to assess the impact of GPS on urologist's treatment preference for favorable risk prostate cancer (PCa): active surveillance versus active treatment (i.e., prostatectomy/radiation). This is a secondary endpoint from the ENACT trial which recruited from three Chicago hospitals from 2016 to 2019. Methods Ten urologists along with men with very low to favorable‐intermediate risk PCa were included in the study. Participants were randomly assigned to standardized counseling with or without GPS assay. The main outcome was urologists' preference for active treatment at Visit 2 by study arm (GPS versus Control). Multivariable best‐fit binary logistic regressions were constructed to identify factors independently associated with urologists' treatment preference. Results Two hundred men (70% Black) were randomly assigned to either the Control (96) or GPS arm (104). At Visit 2, urologists' preference for prostatectomy/radiation almost doubled in the GPS arm to 29.3% (29) compared to 14.1% (13) in the Control arm (p = 0.01). Randomization to the GPS arm, intermediate NCCN risk level, and lower patient health literacy were predictors for urologists' preference for active treatment. Discussion Limitations included sample size and number of urologists. In this study, we found that GPS testing reduced urologists' likelihood to prefer active surveillance. Conclusions These findings demonstrate how obtaining prognostic biomarkers that predict negative outcomes before treatment decision‐making might influence urologists' preference for recommending aggressive therapy in men eligible for active surveillance.

Background: Somalia has long been in a state of humanitarian crisis; trauma-related mental health needs are extremely high. Access to state-of-the-art mental health care is limited. Islamic Trauma Healing (ITH) is a manualized mosque-based, lay-led group intervention aimed at healing the individual and communal mental wounds of war and refugee trauma. The 6-session intervention combines Islamic principles with empirically-supported exposure and cognitive restructuring principles for posttraumatic stress disorder (PTSD). ITH reduces training time, uses a train the trainers (TTT) model, and relies on local partnerships embedded within the strong communal mosque infrastructure. Methods: We will conduct a hybrid effectiveness-implementation randomized control trial (RCT) in the Somaliland, with implementation in the cities of Hargeisa, Borama, and Burao. In this study, a lay-led, mosque-based intervention, Islamic Trauma Healing (ITH), to promote mental health and reconciliation will be examined in 200 participants, randomizing mosques to either immediate ITH or a delayed (waitlist; WL) ITH conditions. Participants will be assessed by assessors masked to condition at pre, 3 weeks, 6 weeks, and 3-month follow-up. Primary outcome will be assessor-rated posttraumatic stress symptoms (PTSD), with secondary outcomes of depression, somatic symptoms, and well-being. A TTT model will be tested, examining the implementation outcomes. Additional measures include potential mechanisms of change and cost effectiveness. Conclusion: This trial has the potential to provide effectiveness and implementation data for an empirically-based principle trauma healing program for the larger Islamic community who may not seek mental health care or does not have access to such care. Clinical trial registration number: ClinicalTrials.gov NCT05890482. World health organization trial registration data set information: See Supplemental Appendix 1.

[This corrects the article DOI: 10.1371/journal.pone.0258979.].

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Traumatic brain injury (TBI) is associated with increased risk of dementia. However, whether TBI is associated with greater cognitive decline over time in specific cognitive domains among older adults is not well understood. This prospective cohort study used data from 1476 male Vietnam Era Twin Study of Aging participants (average age at study entry = 57.9 years, range = 51?71 years; 97.6% non-Hispanic; 92.5% White) collected from 2003 to 2019, who had complete information on prior TBI. Participants completed a comprehensive neuropsychological assessment at up to three visits over up to a 12-year follow-up period during which they also self-reported their history of TBI. Multivariable, linear mixed-effects models were used to assess associations between TBI and cognitive performance trajectories. Effect measure modification by apolipoprotein E (APOE) epsilon 4 (?4) genotype status was assessed in a subset of participants. Thirty-one percent of participants reported a history of TBI; 29.4% were APOE ?4 carriers. There were no statistically significant associations of TBI with decline in episodic memory, executive function, or processing speed among participants overall. In models stratified by APOE ?4 carrier status, TBI was associated with a larger magnitude of decline in executive function for APOE ?4 carriers (? = ?0.0181; 95% confidence interval [CI] ?0.0335, ?0.0027) compared to noncarriers (? = ?0.0031; 95% CI ?0.0128, 0.0067; PInteraction = 0.03). In sensitivity analyses, TBI earlier in life (before military induction, average age = 20 years) was associated with faster declines in executive function compared to no TBI, irrespective of APOE ?4 status. In this sample of middle-to-older aged men, TBI was associated with faster declines in executive function among APOE ?4 carriers and among those who reported TBI in early life. These findings support the importance of a life course perspective when considering factors that may influence cognitive health in aging.

Abstract Background Most people with opioid use disorder (OUD) have co-occurring substance use, which is associated with lower receipt of OUD medications (MOUD). Expanding MOUD provision and care linkage outside of substance use disorder (SUD) specialty settings is a key strategy to increase access. Therefore, it is important to understand how MOUD providers in these settings approach care for patients with co-occurring substance use. This qualitative study of Veterans Health Administration (VA) clinicians providing buprenorphine care in primary care, mental health, and pain settings aimed to understand (1) their approach to addressing OUD in patients with co-occurring substance use, (2) perspectives on barriers/facilitators to MOUD receipt for this population, and (3) support needed to increase MOUD receipt for this population. Methods We interviewed a purposive sample of 27 clinicians (12 primary care, 7 mental health, 4 pain, 4 pharmacists) in the VA northwest network. The interview guide assessed domains of the Tailored Implementation for Chronic Diseases Checklist. Interviews were transcribed and qualitatively analyzed using inductive content analysis. Results Participants reported varied approaches to identifying co-occurring substance use and addressing OUD in this patient population. Although they reported that this topic was not clearly addressed in clinical guidelines or training, participants generally felt that patients with co-occurring substance use should receive MOUD. Some viewed their primary role as providing this care, others as facilitating linkage to OUD care in SUD specialty settings. Participants reported multiple barriers and facilitators to providing buprenorphine care to patients with co-occurring substance use and linking them to SUD specialty care, including provider, patient, organizational, and external factors. Conclusions Efforts are needed to support clinicians outside of SUD specialty settings in providing buprenorphine care to patients with co-occurring substance use. These could include clearer guidelines and policies, more specific training, and increased care integration or cross-disciplinary collaboration. Simultaneously, efforts are needed to improve linkage to specialty SUD care for patients who would benefit from and are willing to receive this care, which could include increased service availability and improved referral/hand-off processes. These efforts may increase MOUD receipt and improve OUD care quality for patients with co-occurring substance use.

ABSTRACT Staphylococcus saprophyticus is the leading Gram-positive cause of uncomplicated urinary tract infections. Recent reports of increasing antimicrobial resistance (AMR) in S. saprophyticus warrant investigation of its understudied resistance patterns. Here, we characterized a diverse collection of S. saprophyticus (n = 275) using comparative whole genome sequencing. We performed a phylogenetic analysis of core genes (1,646) to group our S. saprophyticus and investigated the distributions of antibiotic resistance genes (ARGs). S. saprophyticus isolates belonged to two previously characterized lineages, and 14.91% (41/275) demonstrated multidrug resistance. We compared antimicrobial susceptibility phenotypes of our S. saprophyticus with the presence of different ARGs and gene alleles. 29.8% (82/275) carried staphylococcal cassette chromosome mobile elements, among which 25.6% (21/82) were mecA+. Penicillin resistance was associated with the presence of mecA or blaZ. The mecA gene could serve as a marker to infer cefoxitin and oxacillin resistance of S. saprophyticus, but the absence of this gene is not predictive of susceptibility. Utilizing computational modeling, we found several genes were associated with cefoxitin and oxacillin resistance in mecA− isolates, some of which have predicted functions in stress response and cell wall synthesis. Furthermore, phenotype association analysis indicates ARGs against non-β-lactams reported in other staphylococci may serve as resistance determinants of S. saprophyticus. Lastly, we observed that two ARGs [erm and erm (44)v], carried by bacteriophages, were correlated with high phenotypic non-susceptibility against erythromycin (11/11 and 10/10) and clindamycin (11/11 and 10/10). The AMR-correlated genetic elements identified in this work can help to refine resistance prediction of S. saprophyticus during antibiotic treatment.IMPORTANCEStaphylococcus saprophyticus is the second most common bacteria associated with urinary tract infections (UTIs) in women. The antimicrobial treatment regimen for uncomplicated UTI is normally nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), or a fluoroquinolone without routine susceptibility testing of S. saprophyticus recovered from urine specimens. However, TMP-SMX-resistant S. saprophyticus has been detected recently in UTI patients, as well as in our cohort. Herein, we investigated the understudied resistance patterns of this pathogenic species by linking genomic antibiotic resistance gene (ARG) content to susceptibility phenotypes. We describe ARG associations with known and novel SCCmec configurations as well as phage elements in S. saprophyticus, which may serve as intervention or diagnostic targets to limit resistance transmission. Our analyses yielded a comprehensive database of phenotypic data associated with the ARG sequence in clinical S. saprophyticus isolates, which will be crucial for resistance surveillance and prediction to enable precise diagnosis and effective treatment of S. saprophyticus UTIs.

Purpose: Evaluate perceptions of a 12-week in-person physical activity intervention for endometrial cancer survivors with obesity. Methods: Sixteen endometrial cancer survivors (Age: 64 ± 8 yrs) with obesity (BMI: 34 ± 8 kg·m−2) who completed a 12-week comprehensive physical activity program completed semi-structured interviews regarding perceptions of physical activity participation. Transcripts were analyzed using thematic analysis and were confirmed by multiple authors. Results: Emergent themes (and subthemes) were: 1) Routine physical activity (Walking, Chores), 2) Motivations for physical activity (Social, Independence, Health, Family, Weight), 3) Barriers to physical activity (Weather, Pain, Fatigue, Family Stress), 4) Motivation to 12-week program adherence (Social, Fun, Caring, Structure, Shared Experiences), 5) Perceived benefits of the program (Social, Self-efficacy, Activities of Daily Living, Body Composition, Well-being, Health), and 6) Feedback about the 12-week program (Timing, Setting, Exercise Modes, Incentives, Instructor, Learning). Conclusions: Socioculturally diverse cancer survivors with obesity who were able to complete a 12-week physical activity program emphasized the importance of maintaining independence, and being part of a fun, caring, and social environment for their ability to overcome fatigue, pain, and family stresses to adhere to the program. Participants discussed myriad health and wellness benefits, and wished the program were more robust. Implications for Cancer Survivors: Low-burden exercise programs can confer meaningful health and wellness benefits for cancer survivors. To maintain adherence, programs should emphasize social cohesion and exercises to help maintain independence. Instructors should express caring support while also making classes fun, while emphasizing body composition instead of weight loss.

IntroductionCardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia.MethodsThis study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points.ResultsHDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males.DiscussionFindings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

Indices such as the Index of Biotic Integrity (IBI) are often used by management agencies to estimate the abstract property of stream health. These indices are usually predicated on the belief that certain fish species are tolerant to environmental perturbation while others are sensitive. Species are usually designated as either tolerant or sensitive in these analyses based on inherent ecological or taxonomic characteristics. However, previous literature has shown that certain species from ecological or taxonomic “sensitive” groups experience increased abundance in degraded streams. We term such species “cryptic tolerants”. Using a stream fish assemblage dataset of 433 unique sample locations across the state of Alabama and the National Landcover Dataset, our objectives were to 1) identify the most common cryptic tolerant species, 2) investigate how cryptic tolerant species might inflate indices of stream health, and 3) compare an alternative measure of stream health in which species are statistically defined rather than defined using the traditional trait-based approach. We identified cryptic tolerants using Nonmetric Multidimensional Scaling in six ecoregions. A series of regressions revealed that the proportion of cryptic tolerant species decreased in response to an increasing proportion of forested land in catchments while the proportion of true sensitives increased in all ecoregions except for the Cumberland Plateau. An index that simply used the percentage of statistically defined, non-tolerant species generally had lower p-values and higher r2 values than IBI scores when both were regressed against percentage of forest in catchment. However, both indices had low degrees of correlation with expected disturbance, indicating a univariate index may be inadequate to characterize stream health. Our results highlight a potential issue with applying the IBI to diverse southeastern systems in the United States, which may be alleviated by designating species sensitivity based on empirical response to disturbance rather than taxonomic or ecological characteristics.

Many individuals practicing field-based research are subjected to sexual harassment and assault. This fact holds true for people engaged in archaeological field research and may be true for students who are just learning field methods while enrolled in an archaeological field school. We review some of our current research on the means of reducing and preventing sexual harassment and assault at archaeological field schools, as well as ways to create safer, more inclusive learning spaces. Additionally, we suggest that for the discipline to advance field school teaching and learning, we, as field directors, must situate ourselves as active and advocacy anthropologists: an approach that puts our students as a central focus when developing field-based pedagogy. As the authors of this work, we review our identities and positionality in conducting this research and in making meaning from the data we have collected.

ABSTRACT Proteus mirabilis is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria, P. mirabilis may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of P. mirabilis genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060 Proteus genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related P. mirabilis genomes, and pan-genome annotation to identify genes of interest not present in the model P. mirabilis strain HI4320. Within our cohort, Proteus is composed of 10 named species and 5 uncharacterized genomospecies. P. mirabilis can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The P. mirabilis pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain P. mirabilis HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome. IMPORTANCE Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on P. mirabilis, but similar to other Gram-negative bacteria, P. mirabilis has a mosaic genome with a linkage between phylogenetic position and accessory genome content. P. mirabilis encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.

IntroductionDaily oral pre-exposure prophylaxis (PrEP) is a safe and effective HIV prevention method for pregnant and postpartum women, but adherence barriers exist. Understanding the role of male partners in supporting PrEP use may inform strategies to support PrEP adherence among pregnant and breastfeeding women.MethodsTo understand male partners’ involvement in women's use of PrEP, we conducted in-depth interviews with pregnant women in Lilongwe, Malawi who had recently decided to use PrEP (n = 30) and their male partners (n = 20) in the context of a PrEP adherence trial. Women were purposively recruited to ensure variation in their partners’ HIV status. Interviews were conducted in Chichewa using a semistructured guide. We followed a thematic approach to analyze the interview data.ResultsMost male partners were receptive to women using PrEP during pregnancy because it eased their fears of the woman and baby acquiring HIV. Men often played a key role in women's PrEP adherence by providing daily reminders and encouragement to adhere to their medication. The majority of women appreciated this support from the men as it lessened the burden of remembering to take their medications daily on their own and aided their adherence. However, several women who lacked male partner support spoke of wanting their partners to be more involved. Many men living with HIV found the mutual support beneficial for their antiretroviral therapy adherence, while men without HIV or with status unknown appreciated knowing that the family was protected. While most men were open to women continuing PrEP beyond the current study, some would only support it if women were still at risk for acquiring HIV.ConclusionIn this study, male partners were strongly motivated to support the PrEP adherence of their female partners as a way of ensuring that the pregnant women and unborn babies were protected against HIV. Promoting disclosure and tangible support that arises organically among men may be helpful, but programs to enhance this support and identify ways to support women who do not receive support from their partners or do not wish to disclose their PrEP use to partners may be needed.

Abstract Background Blood-based neurofilament light chain (NfL) is a promising biomarker of neurodegeneration across multiple neurodegenerative diseases. However, blood-based NfL is highly associated with renal function in older adults, which leads to the concern that blood-based NfL levels may be influenced by renal function, rather than neurodegeneration alone. Despite growing interest in using blood-based NfL as a biomarker of neurodegeneration in research and clinical practices, whether renal function should always be accounted for in these settings remains unclear. Moreover, the mechanisms underlying this association between blood-based measures of NfL and renal function remain elusive. In this study, we first evaluated the effect of renal function on the associations of plasma NfL with other measures of neurodegeneration. We then examined the extent of genetic and environmental contributions to the association between plasma NfL and renal function. Methods In a sample of 393 adults (mean age=75.22 years, range=54–90), we examined the associations of plasma NfL with cerebrospinal fluid (CSF) NfL and brain volumetric measures before and after adjusting for levels of serum creatinine (an index of renal function). In an independent sample of 969 men (mean age=67.57 years, range=61–73) that include monozygotic and dizygotic twin pairs, we replicated the same analyses and leveraged biometrical twin modeling to examine the genetic and environmental influences on the plasma NfL and creatinine association. Results Plasma NfL’s associations with cerebrospinal fluid NfL and brain volumetric measures did not meaningfully change after adjusting for creatinine levels. Both plasma NfL and creatinine were significantly heritable (h 2=0.54 and 0.60, respectively). Their phenotypic correlation (r=0.38) was moderately explained by shared genetic influences (genetic correlation=0.46) and unique environmental influences (unique environmental correlation=0.27). Conclusions Adjusting for renal function is unnecessary when assessing associations between plasma NfL and other measures of neurodegeneration but is necessary if plasma NfL is compared to a cutoff for classifying neurodegeneration-positive versus neurodegeneration-negative individuals. Blood-based measures of NfL and renal function are heritable and share common genetic influences.

Objective: To examine trends of frozen embryo transfer (FET) proportions and large-for-gestational-age (LGA) incidence and determine risk factors for LGA infants after FET. Design: Retrospective cohort study. Setting: Not applicable. Patient(s): Frozen embryo transfer cycles. Intervention(s): None. Main Outcome Measure(s): Singleton LGA infant. Result(s): The percentage of FETs increased from 20%–74% of transfers, whereas the rate of LGA among FET singleton births decreased from 18%–12% during 2004–2018. In a subanalysis of 127,525 FET-associated singleton live births during 2016–2018, patient factors associated with LGA were higher-than-normal maternal body mass index (body mass index [BMI], 25.0–29.9 kg/m2; adjusted relative risk [aRR], 1.31; 95% confidence interval [CI], 1.26–1.36; BMI, 30.0–34.9 kg/m2; aRR, 1.48; 95% CI, 1.41–1.55; and BMI, >35 Kg/m2; aRR, 1.68; 95% CI, 1.59–1.77) and ≥1 prior birth vs. none. Low maternal BMI (

Abstract Background Fidelity measurement of implementation strategies is underdeveloped and underreported, and the level of reporting is decreasing over time. Failing to properly measure the factors that affect the delivery of an implementation strategy may obscure the link between a strategy and its outcomes. Barriers to assessing and reporting implementation strategy fidelity among researchers are not well understood. The aims of this qualitative study were to identify barriers to fidelity measurement and pragmatic pathways towards improvement. Methods We conducted in-depth interviews among researchers conducting implementation trials. We utilized a theory-informed interview approach to elicit the barriers and possible solutions to implementation strategy fidelity assessment and reporting. Reflexive-thematic analysis guided coding and memo-writing to determine key themes regarding barriers and solutions. Results Twenty-two implementation researchers were interviewed. Participants agreed that implementation strategy fidelity was an essential element of implementation trials and that its assessment and reporting should improve. Key thematic barriers focused on (1) a current lack of validated fidelity tools with the need to assess fidelity in the short term, (2) the complex nature of some implementation strategies, (3) conceptual complications when assessing fidelity within mechanisms-focused implementation research, and (4) structural issues related to funding and publishing. Researchers also suggested pragmatic solutions to overcome each barrier. Respondents reported using specification and tracking data in the short term until validated tools become available. Participants suggested that researchers with strategy-specific content expertise lead the way in identifying core components and setting fidelity requirements for them. Addressing the third barrier, participants provided examples of what pragmatic prospective and retrospective fidelity assessments might look like along a mechanistic pathway. Finally, researchers described approaches to minimize costs of data collection, as well as more structural accountability like adopting and enforcing reporting guidelines or changing the structure of funding opportunities. Discussion We propose short- and long-term priorities for improving the assessment and reporting of implementation strategy fidelity and the quality of implementation research. Conclusions A better understanding of the barriers to implementation strategy fidelity assessment may pave the way towards pragmatic solutions.

Abstract Background Fetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity. Methods Mother–child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (

Abstract We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

Background: Evidence supports an important link between mitochondrial DNA (mtDNA) variation and adverse drug reactions such as idiosyncratic drug-induced liver injury (iDILI). Here, we describe the generation of HepG2-derived transmitochondrial cybrids, to investigate the impact of mtDNA variation on mitochondrial (dys)function and susceptibility to iDILI. This study created 10 cybrid cell lines, each containing distinct mitochondrial genotypes of haplogroup H or haplogroup J backgrounds. Methods: HepG2 cells were depleted of mtDNA to make rho zero cells, before the introduction of known mitochondrial genotypes using platelets from healthy volunteers (n=10), thus generating 10 transmitochondrial cybrid cell lines. The mitochondrial function of each was assessed at basal state and following treatment with compounds associated with iDILI; flutamide, 2-hydroxyflutamide, and tolcapone, and their less toxic counterparts bicalutamide and entacapone utilizing ATP assays and extracellular flux analysis. Results: Whilst only slight variations in basal mitochondrial function were observed between haplogroups H and J, haplogroup-specific responses were observed to the mitotoxic drugs. Haplogroup J showed increased susceptibility to inhibition by flutamide, 2-hydroxyflutamide, and tolcapone, via effects on selected mitochondrial complexes (I and II), and an uncoupling of the respiratory chain. Conclusions: This study demonstrates that HepG2 transmitochondrial cybrids can be created to contain the mitochondrial genotype of any individual of interest. This provides a practical and reproducible system to investigate the cellular consequences of variation in the mitochondrial genome, against a constant nuclear background. Additionally, the results show that inter-individual variation in mitochondrial haplogroup may be a factor in determining sensitivity to mitochondrial toxicants. Funding: This work was supported by the Centre for Drug Safety Science supported by the Medical Research Council, United Kingdom (Grant Number G0700654); and GlaxoSmithKline as part of an MRC-CASE studentship (grant number MR/L006758/1).

Abstract Background Leadership commitment to worker safety and health is one of the most important factors when organizations develop and implement a Total Worker Health® approach. We aimed to assess the effectiveness of a Total Worker Health (“TWH”) leadership development program that targeted owners and other senior-level leadership positions on changing organizational and worker outcomes from baseline to one-year later. Methods The Small + Safe + Well study included small businesses from a variety of industries in the state of Colorado, USA that were participating in Health Links™. We designed a randomized waitlisted control comparison design (RCT) to evaluate the added benefit of a TWH leadership development program. An employer assessment tool was used to assess TWH policies and programs, and an employee health and safety survey was used to assess safety leadership and health leadership practices, safety climate and health climate, safety behaviors and health behaviors, and well-being. We used a linear mixed model framework with random effects for business and employee to assess the impact of intervention on the outcomes of interest. Results Thirty-six businesses (37% retention) and 250 employees (9% retention) met the RCT study inclusion criteria and were included in the analysis. Businesses improved their TWH policies and programs score from baseline to one-year later, regardless of leadership intervention group assignment. Neither intervention group demonstrated improvements in employee-reported outcomes. Conclusions This study sought to address a gap in the literature regarding small business senior leadership development for TWH. Our study demonstrates many of the challenges of conducting studies focused on organizational change in workplaces, specifically in small businesses. When designing TWH intervention studies, researchers should consider how to best engage small business leaders in interventions and implementations early on, as well as methods that are well matched to measuring primary and secondary outcomes longitudinally. Future research is needed to test the feasibility and sustainability of TWH interventions in small business. Trial registration The trial was retrospectively registered with ClinicalTrials.gov ( ID U19OH011227 ).

Prior abdominal liposuction can be viewed as a relative or absolute contraindication to abdominally based autologous breast reconstruction given concerns for damaged perforators and scarring complicating intraoperative dissection. This systematic review aims to explore the outcomes of abdominally based breast reconstruction in patients with a history of abdominal liposuction. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided literature search was conducted using PubMed, Scopus, and Web of Science from the earliest available date through June 2020. Deep inferior epigastric perforator, muscle-sparing transverse rectus abdominis musculocutaneous (TRAM), superficial inferior epigastric artery, and pedicled TRAM flaps were included for evaluation. Complications included total or partial flap loss, fat necrosis, seroma, delayed wound healing, and donor site complications. After inclusion criteria were applied, 336 nonduplicate articles were screened, yielding 11 for final review, representing 55 flaps in 43 patients. There was no instance of total flap loss, eight (14.5%) flaps developed partial loss or fat necrosis, three (5.4%) flaps had delayed wound healing, and two (4.6%) patients had donor site complications. Most authors (8/11) utilized some type of preoperative imaging. Doppler ultrasonography was the most used modality, and these patients had the lowest rate of partial flap loss or flap fat necrosis (8%), followed by those without any preoperative imaging (10%). In conclusion, this review supports that patients undergoing abdominally based autologous breast reconstruction with a history of abdominal liposuction are not at an increased risk of flap or donor site complications. Although preoperative imaging was common, it did not reliably decrease complications. Further prospective studies are needed to address the role of imaging in improving outcomes.

Abstract Background Improved methodology to measure acute phase proteins and determination of lipoprotein particle‐size distribution (PSD) could be clinically useful in dogs with systemic inflammatory processes. Objectives Evaluate an immunoturbidometric assay for serum amyloid A (SAA) and lipoprotein PSD in dogs with sepsis, nonseptic systemic inflammation, and in healthy controls. Correlate dyslipidemic changes with SAA and C‐reactive protein (CRP) concentrations. Animals Twenty‐five dogs with sepsis, 15 dogs with nonseptic systemic inflammation, and 22 healthy controls. Methods Prospective, case‐control study. Variables included SAA, CRP, and electrophoretic subfractionation of high‐ and low‐density lipoproteins (HDL, LDL). Continuous variables were compared using ANOVA or Kruskal‐Wallis tests with linear regression or Spearman's rank correlation used to assess relationships between variables. Results Median SAA and CRP concentrations were greater in dogs with sepsis (SAA 460 mg/L, interquartile range [IQR] 886 mg/L; CRP 133.2 mg/L, IQR 91.6 mg/L) and nonseptic inflammation (SAA 201 mg/L, IQR 436 mg/L; CRP 91.1 mg/L, IQR 88.6 mg/L) compared to healthy dogs (SAA 0.0 mg/L, IQR 0.0 mg/L; CRP 4.9 mg/L, IQR 0.0 mg/L) P 677.5 mg/L SAA was 43.2% sensitive and 92.3% specific for sepsis. Low‐density lipoprotein was higher in dogs with sepsis 29.6%, (mean, SD 14.6) compared to 14.4% (mean, SD 5.6) of all lipoproteins in healthy controls (P = .005). High‐density lipoprotein was not associated with CRP but was negatively correlated with SAA (rs −0.47, P

A meta-analysis of genome-wide association studies of circulating total-tau levels identifies loci specific to European or African American ancestries, providing further insight to the genetic etiology of neurological diseases.

Background: Studies have investigated white matter microstructure in relation to late-life cognitive impairments, with fractional anisotropy (FA) and mean diffusivity (MD) measures thought to capture demyelination and axonal degradation. However, new post-processing methods allow isolation of free water (FW), which captures extracellular fluid contributions such as atrophy and neuroinflammation, from tissue components. FW also appears to be highly relevant to late-life cognitive impairment. Here, we evaluated whether executive functions are associated with FW, and FA and MD corrected for FW (FAFWcorr and MDFWcorr). Method: We examined 489 non-demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Two latent factors capturing ‘common executive function’ and ‘working-memory specific’ processes were estimated based on 6 tasks. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FAFWcorr, and MDFWcorr. Results: Better ‘common executive function’ was associated with lower FW across 9 of the 11 tracts. There were no significant associations with intracellular metrics after false discovery rate correction. Effects also appeared driven by individuals with MCI (13.7% of the sample). Working memory-specific tasks showed some associations with FAFWcorr, including the triangularis portion of the inferior frontal gyrus. There was no evidence that cognitive reserve (i.e., general cognitive ability assessed in early adulthood) moderated these associations between executive function and FW or FA. Discussion: Executive function abilities in early old age are associated primarily with extracellular fluid (FW) as opposed to white matter (FAFWcorr or MDFWcorr). Moderation analyses suggested cognitive reserve does not play a strong role in these associations, at least in this sample of non-demented men.

ObjectiveThere is scant research on the effectiveness of permanent supportive housing for homeless women with mental illness. This study examines the effectiveness of Housing First with an unprecedentedly large sample of homeless women from five Canadian cities, and explore baseline risk factors that predict social, health and well-being outcomes over a 24 month-period.MethodsThe At Home/Chez Soi multi-site randomized controlled Housing First trial recruited over 600 women between October 2009 and July 2011. This is a post-hoc subgroup exploratory analysis of self-identified women with at least one follow-up interview who were randomized to Housing First (HF) (n = 374) or treatment-as-usual (TAU) (n = 279) and had at least one follow-up interview. Linear mixed models and generalized estimating equations were used after multiple imputation was applied to address missing data.ResultsAt the end of follow-up, the mean percentage of days spent stably housed was higher for women in the intervention 74.8% (95%CI = 71.7%-77.8%) compared with women in the treatment-as-usual group, 37.9% (95%CI = 34.4%-41.3%), pConclusionsHousing First interventions ensured that women experiencing homelessness are quickly and consistently stably housed. However, they did not differentially impact health and social measures compared to treatment as usual. Ensuring positive health and social outcomes may require greater supports at enrolment for subgroups such as those with low educational attainment, and additional attention to severity of baseline mental health challenges, such as suicidality.Trial registrationInternational Standard Randomized Control Trial Number Register Identifier: ISRCTN42520374.

Abstract Background Chronic psychotic disorders (CPD) impose a particularly significant burden in resource-limited settings. Combining long-acting antipsychotic medication (LAI) with a customized adherence enhancement intervention (CAE-L) has potential to advance care. Methods Nineteen adults ≥ age 18 with CPD who self-reported missing ≥20% of antipsychotic medication within the last month were stabilized on oral haloperidol prior to transitioning to monthly haloperidol decanote for 25 weeks. Outcome evaluations were conducted at baseline and Week 25. Primary outcomes were oral medication adherence assessed via the Tablet Routines Questionnaire (TRQ) and LAI injection frequency. Secondary outcomes included CPD symptoms measured by the Brief Psychiatric Rating Scale and Clinical Global Impressions, functioning evaluated using the Social and Occupational Functioning Scale, and medication attitudes assessed with the Drug Attitudes Inventory. Results Mean sample age was 38.79 (SD = 9.31) with 18 individuals completing the study. There was one serious adverse event, a relapse into substance use, not deemed study-related. Mean endpoint LAI dosage was 65.79 mg (SD = 22.38). TRQ mean scores were 21.84 (SD =13.83) and 12.94 (SD = 11.93) at screen and baseline respectively. For only two individuals who were on concomitant oral medication at 25 weeks, TRQ change was not calculated. LAI injection frequency was 100%. Medication attitudes scores significantly improved from 7.89 (SD = 2.72) to 9.83 (SD = 0.52) (p = .001.) Changes in CPD symptoms and functioning were non-significant. Conclusions CAE-L appears to be preliminarily feasible and acceptable in Tanzanians with CPD. Trial registration The study was registered on ClinicalTrials.gov (NCT04327843) on March 31, 2020.

Abstract Background Poppy seeds contain morphine and other opioid alkaloids and are commercially available in the United States. Users of poppy seed tea (PST) can consume several hundred morphine milligram equivalents per day, and opioid dependence from PST use can develop. We report a case of a patient with chronic pain and PST use leading to opioid use disorder (OUD). This case represents the first published report of OUD from PST successfully treated with buprenorphine (BUP) in a primary care setting. The provider in this case used a unique model of care with an opioid prescribing support team to deliver safe and effective care. Case presentation A 47-year-old man with chronic pain and prescription opioid use presented to primary care to discuss a flare of shoulder pain, and revealed in subsequent conversation a long-standing use of PST to supplement pain control. Attempts at cessation resulted in severe withdrawal symptoms, leading to return to PST use. The primary care provider consulted the VA Puget Sound SUpporting Primary care Providers in Opioid Risk reduction and Treatment (SUPPORT) team to evaluate the patient for OUD. The patient discontinued all opioids, and initiated BUP under the supervision of the primary care provider. He remained on a stable dosage, without relapse, 24 months later. Conclusions PST, which can be made through purchase of readily available poppy pods, carries risk for development of OUD and overdose. Herein we highlight the utility of a primary care opioid prescribing support team in empowering a primary care provider to prescribe BUP to treat a patient with complex OUD.

Abstract The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p

Providing equitable support for people experiencing communication disability (CD) globally is a historical and contemporary challenge for the speech–language therapy profession. A group of speech–language therapists (SLTs) with ongoing and sustained experiences in Majority and Minority World contexts participated in five virtual meetings in 2021. The aim of these meetings was to develop provocative statements that might spur a global discussion among individuals and organisations that support people experiencing CD. The following questions were discussed: What is our vision for the future of the profession globally? What are the global challenges around access to speech–language therapy services? Four main themes emerged: (1) the need to centre people experiencing CD as the focal point of services, (2) participation, (3) equity and (4) community. The themes relate to the need for a process of de-imperialism in the profession. Suggestions were made to develop more suitable terminology and to establish a global framework that promotes more equitable access to communication services. We seek the adoption of approaches that focus on reciprocal global engagement for capacity strengthening. Alternative models of culturally sustaining and equitable service delivery are needed to create impact for people experiencing CD, and their families worldwide. Contribution: Provocative statements were developed to prompt global conversations among speech–language therapy professionals and associations. We encourage readers to consider the questions posed, share their viewpoints and initiate positive change towards a global strategy.

ABSTRACT The prevalence of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Escherichia coli has been increasing, with this spread driven by ESBL-encoding plasmids. However, the epidemiology of ESBL-disseminating plasmids remains understudied, obscuring the roles of individual plasmid lineages in ESBL spread. To address this, we performed an in-depth genomic investigation of 149 clinical ESBL-like E. coli isolates from a tertiary care hospital. We obtained high-quality assemblies for 446 plasmids, revealing an extensive map of plasmid sharing that crosses time, space, and bacterial sequence type boundaries. Through a sequence-based network, we identified specific plasmid lineages that are responsible for the dissemination of major ESBLs. Notably, we demonstrate that IncF plasmids separate into 2 distinct lineages that are enriched for different ESBLs and occupy distinct host ranges. Our work provides a detailed picture of plasmid-mediated spread of ESBLs, demonstrating the extensive sequence diversity within identified lineages, while highlighting the genetic elements that underlie the persistence of these plasmids within the clinical E. coli population. IMPORTANCE The increasing incidence of nosocomial infections with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli represents a significant threat to public health, given the limited treatment options available for such infections. The rapid ESBL spread is suggested to be driven by localization of the resistance genes on conjugative plasmids. Here, we identify the contributions of different plasmid lineages in the nosocomial spread of ESBLs. We provide further support for plasmid-mediated spread of ESBLs but demonstrate that some ESBL genes rely on dissemination through plasmids more than the others. We identify key plasmid lineages that are enriched in major ESBL genes and highlight the encoded genetic elements that facilitate the transmission and stable maintenance of these plasmid groups within the clinical E. coli population. Overall, our work provides valuable insight into the dissemination of ESBLs through plasmids, furthering our understating of factors underlying the increased prevalence of these genes in nosocomial settings.

Abstract Background The Total Worker Health® (TWH) approach is a best practice method to protect and promote worker safety, health, and well-being. Central to this approach is leadership support and health and safety climates that support day-to-day use of health and safety policies and programs. There is some research that supports these relationships, but there is limited research amongst small businesses. Furthermore, it remains to be shown what role TWH business strategies, as reflected by organizational policies and programs, play in this process. The purpose of this study is to characterize small businesses by their organizations’ TWH approach and assess the relationship of these approaches to employee health and safety behaviors. Methods We utilized cross-sectional data from 97 businesses participating in the Small+Safe+Well study. We collected data using a business assessment tool, Healthy Workplace Assessment™, and an employee assessment tool, Employee Health and Safety Culture Survey. We used latent profile analysis at the business level to identify subgroups of businesses based on a set of characteristics from these assessments. Linear regression analysis at the employee level was used to determine profile association with employee safety and health behaviors. Results There were two profiles characterized by the lowest (33% of all businesses) and highest (9%) levels of the indicators. There were also two profiles with higher scores on two of the different foci on either TWH business strategies (27%) or leadership and climate (31%). Employees working for a business with a profile that focused on leadership and climate, in addition to having a business strategy, reported the best safety and health behaviors. Conclusions Our study demonstrates that employee engagement in TWH will be highest when businesses have a strategy for how they implement a TWH approach and when they demonstrate leadership commitment to these strategies and foster positive safety and health climates. Our results offer suggestions on how to use TWH assessments to develop interventions for small businesses. More research is needed to understand whether small businesses can improve upon their profile overtime, whether these changes depend on contextual factors, and whether TWH interventions can help them improve their profile.

Cognitive reserve and related constructs are valuable for aging-related research, but consistency and clarification of terms is needed as there is still no universally agreed upon nomenclature. We propose a new set of definitions for the concepts of reserve, maintenance, and resilience, and we invoke parallel concepts for each that are applicable to cognition and to brain. Our definitions of reserve and resilience correspond reasonably well to dictionary definitions of these terms. We demonstrate logical/methodological problems that arise from incongruence between commonly used conceptual and operational definitions. In our view, cognitive reserve should be defined conceptually as one’s total cognitive resources at a given point in time. IQ and education are examples of common operational definitions (often referred to as proxies) of cognitive reserve. Many researchers define cognitive reserve conceptually as a property that allows for performing better than expected cognitively in the face of aging or pathology. Performing better than expected is demonstrated statistically by interactions in which the moderator is typically IQ or education. The result is an irreconcilable situation in which cognitive reserve is both the moderator and the moderation effect itself. Our proposed nomenclature resolves this logical inconsistency by defining performing better than expected as cognitive resilience. Thus, in our usage, we would test the hypothesis that high cognitive reserve confers greater cognitive resilience. Operational definitions (so-called proxies) should not conflate factors that may influence reserve—such as occupational complexity or engagement in cognitive activities—with cognitive reserve itself. Because resources may be depleted with aging or pathology, one’s level of cognitive reserve may change over time and will be dependent on when assessment takes place. Therefore, in addition to cognitive reserve and cognitive resilience, we introduce maintenance of cognitive reserve as a parallel to brain maintenance. If, however, education is the measure of reserve in older adults, it precludes assessing change or maintenance of reserve. Finally, we discuss consideration of resistance as a subcategory of resilience, reverse causation, use of residual scores to assess performing better than expected given some adverse factor, and what constitutes high vs. low cognitive reserve across different studies.

ObjectiveCognitive practice effects (PEs) can delay detection of progression from cognitively unimpaired to mild cognitive impairment (MCI). They also reduce diagnostic accuracy as suggested by biomarker positivity data. Even among those who decline, PEs can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and thus impede detection of further impairment. Within an MCI sample at baseline, we evaluated how PEs impact prevalence, reversion rates, and dementia progression after 1 year.MethodsWe examined 329 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age = 73.1; SD = 7.4). We identified test-naïve participants who were demographically matched to returnees at their 1-year follow-up. Since the only major difference between groups was that one completed testing once and the other twice, comparison of scores in each group yielded PEs. PEs were subtracted from each test to yield PE-adjusted scores. Biomarkers included cerebrospinal fluid phosphorylated tau and amyloid beta. Cox proportional models predicted time until first dementia diagnosis using PE-unadjusted and PE-adjusted diagnoses.ResultsAccounting for PEs increased MCI prevalence at follow-up by 9.2% (272 vs. 249 MCI), and reduced reversion to normal by 28.8% (57 vs. 80 reverters). PEs also increased stability of single-domain MCI by 12.0% (164 vs. 147). Compared to PE-unadjusted diagnoses, use of PE-adjusted follow-up diagnoses led to a twofold increase in hazard ratios for incident dementia. We classified individuals as false reverters if they reverted to cognitively unimpaired status based on PE-unadjusted scores, but remained classified as MCI cases after accounting for PEs. When amyloid and tau positivity were examined together, 72.2% of these false reverters were positive for at least one biomarker.InterpretationEven when PEs are small, they can meaningfully change whether some individuals with MCI retain the diagnosis at a 1-year follow-up. Accounting for PEs resulted in increased MCI prevalence and altered stability/reversion rates. This improved diagnostic accuracy also increased the dementia-predicting ability of MCI diagnoses.

ABSTRACT Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S. aureus skin and soft tissue infections (SSTI), skin swabs were collected from the anterior nares, axillae, and inguinal folds of 14 participants at 1- to 3-month intervals over 24 months. Four household members experienced SSTI during the first 12-months (observational period) and were prescribed a 5-day decolonization regimen with intranasal mupirocin and bleach water baths at the 12-month study visit. We sequenced the 16S rRNA gene V1–V2 region and compared bacterial community characteristics between the pre- and post-intervention periods and between younger and older subjects. The median Shannon diversity index was stable during the 12-month observational period at all three body sites. Bacterial community characteristics (diversity, stability, and taxonomic composition) varied with age. Among all household members, not exclusively among the four performing decolonization, diversity was unstable throughout the year post-intervention. In the month after decolonization, bacterial communities were changed. Although communities largely returned to their baseline states, relative abundance of some taxa remained changed throughout the year following decolonization (e.g., more abundant Bacillus; less abundant Cutibacterium). This 5-day decolonization regimen caused disruption of skin bacteria, and effects differed in younger and older subjects. Some effects were observed throughout the year post-intervention, which emphasizes the need for better understanding of the collateral effects of decolonization for S. aureus eradication. IMPORTANCE Decolonization with topical antimicrobials is frequently prescribed to prevent Staphylococcus aureus infection, but the effects on commensal skin bacteria are undetermined. We found that decolonization with mupirocin and bleach water baths leads to sustained disruption of bacterial communities.

Abstract Background Total physical activity is positively associated with brain volume and cognition in older adults. While we have ample evidence that recreational physical activity influences brain health, the contributions of other daily activities are less understood. In particular, the associations between household physical activity and brain health in older adults is underexplored. The purpose of this study was to identify associations between household physical activity, brain volume, and cognition in a sample of cognitively unimpaired older adults. Methods We report data from 66 cognitively unimpaired older adults (71 ± 4 years) who participated in a health evaluation, cognitive assessment, and structural brain imaging. Physical activity was assessed using the Phone-FITT questionnaire and separated into household and recreational physical activity. We quantified whole brain volume, gray matter volume, and white matter volume, and assessed cognitive performance in four domains: memory, working memory/attention, processing speed, and executive function. Associations between physical activity, brain volume, and cognition were investigated in an omnibus approach using two multivariate analysis of variance (MANOVA) models. The first model assessed the associations between physical activity and brain volume adjusting for age, sex, Framingham Risk score (FRS) and intracranial volume. The second model assessed the associations between physical activity and overall cognitive performance adjusting for age, sex, FRS and education. Post hoc regression analyses were conducted to investigate significant MANOVA results. We also conducted further regression analyses to investigate associations with hippocampal and frontal lobe volume. Results Household, but not recreational, physical activity was positively associated with brain volume measurements (F = 3.07, p = .035), specifically gray matter volume (t = 2.51, p = .015). Further exploratory analyses identified that household physical activity was associated with hippocampal (p = .015) and frontal lobe (p = .010) volume. No significant relationships were observed between household or recreational physical activity and cognition. Conclusion Time spent engaging in household physical activity was positively associated with brain volume, specifically gray matter volume, in older adults. Highlighting the benefits associated with household chores may motivate older adults to be more active by providing a more attainable, low risk form of physical activity.

Background: Depression is an established predictor of coronary artery disease (CAD) progression and mortality. “Somatic” symptoms of depression such as fatigue and sleep impairment overlap with symptoms of CAD and independently predict CAD events. Differentiating between “somatic” and “cognitive” depressive symptoms in at-risk patients may improve our understanding of the relationship between depression and CAD. Methods: The study utilized data from the Women's Ischemia Syndrome Evaluation. Participants (N = 641; mean age = 58.0 [11.4] years) were enrolled to evaluate chest pain or suspected myocardial ischemia. They completed a battery of symptom and psychological questionnaires (including the Beck Depression Inventory [BDI]) at baseline, along with quantitative coronary angiography and other CAD diagnostic procedures. The BDI provided scores for total depression and for cognitive and somatic depressive symptom subscales. Results: Two hundred and fourteen (33.4%) women met criteria for obstructive CAD. Logistic regression models were used to examine relationships between depression symptoms and obstructive CAD. Neither BDI total scores (odds ratio [OR] =1.02, 95% confidence interval [CI], 0.99–1.05, P = 0.053) nor BDI cognitive scores (OR = 1.02, 95% CI, 1.00–1.04, P = 0.15) predicted CAD status. BDI somatic symptom scores, however, significantly predicted CAD status and remained statistically significant after controlling for age, race, and education (OR = 1.06, 95% CI, 1.01–1.12, P = 0.02). Conclusion: Among women with suspected myocardial ischemia, somatic but not cognitive depressive symptoms predicted an increased risk of obstructive CAD determined by coronary angiography. Consistent with prior reports, these results suggest a focus on somatic rather than cognitive depressive symptoms could offer additional diagnostic information.

With the aim of better understanding the physical conditions under which Be stars form and evolve, it is imperative to further investigate whether poorly studied young open clusters host Be stars. In this work, we explain how data from Gaia DR2 and DR3 can be combined to recover and characterize active Be stars in open clusters. We test our methodology in four open clusters broadly studied in the literature, known for hosting numerous Be stars. In addition, we show that the disk formation and dissipation approach that is typically used to model long term Be star variability, can explain the observed trends for Be stars in a (GDR3-GDR2) versus GDR3 plot. We propose that extending this methodology to other open clusters, and, in particular, those that are poorly studied, will help to increase the number of Be candidates. Eventually, Be stars may eclipse binary systems in open clusters.

We combine our dynamical modeling black-hole mass measurements from the Lick AGN Monitoring Project 2016 sample with measured cross-correlation time lags and line widths to recover individual scale factors, f , used in traditional reverberation-mapping analyses. We extend our sample by including prior results from Code for AGN Reverberation and Modeling of Emission Lines ( caramel ) studies that have utilized our methods. Aiming to improve the precision of black-hole mass estimates, as well as uncover any regularities in the behavior of the broad-line region (BLR), we search for correlations between f and other AGN/BLR parameters. We find (i) evidence for a correlation between the virial coefficient ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\sigma })$ and black-hole mass, (ii) marginal evidence for a similar correlation between ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ and black-hole mass, (iii) marginal evidence for an anticorrelation of BLR disk thickness with ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\mathrm{FWHM}})$ and ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\mathrm{FWHM}})$ , and (iv) marginal evidence for an anticorrelation of inclination angle with ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\mathrm{FWHM}})$ , ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ , and ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\sigma })$ . Last, we find marginal evidence for a correlation between line-profile shape, when using the root-mean-square spectrum, ${\mathrm{log}}_{10}{(\mathrm{FWHM}/\sigma )}_{\mathrm{rms}}$ , and the virial coefficient, ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ , and investigate how BLR properties might be related to line-profile shape using caramel models.

We present a multiwavelength analysis of the dwarf Seyfert 2 galaxy J144013+024744, a candidate obscured active galactic nucleus (AGN) thought to be powered by an intermediate-mass black hole (IMBH, M _• ≈ 10 ^4 −10 ^6 M _⊙ ) of mass M _• ∼ 10 ^5.2 M _⊙ . To study its X-ray properties, we targeted J144013+024744 with NuSTAR for ≈100 ks. The X-ray spectrum was fitted with an absorbed power law, Pexmon, and a physical model (RXTorus). A Bayesian X-ray analysis was performed to estimate the posteriors. The phenomenological and the physical models suggest the AGN to be heavily obscured by a column density of N _H = (3.4–7.0) × 10 ^23 cm ^−2 . In particular, the RXTorus model with a subsolar metallicity suggests the obscuring column to be almost Compton-thick. We compared the 2–10 keV intrinsic X-ray luminosity with the inferred X-ray luminosities based on empirical scaling relations for unobscured AGNs using L _[O _iv _] 25.89 _ μ _m , L _[O _iii _] _λ _5007 , and L _6 _μ _m and found that the high-excitation [O iv ] line provides a better estimate of the intrinsic 2–10 keV X-ray luminosity ( ${L}_{2\mbox{--}10}^{\mathrm{int}}\sim {10}^{41.41}$ erg s ^−1 ). Our results suggest that J144013+024744 is the first type 2 dwarf galaxy that shows X-ray spectroscopic evidence for obscuration. The column density that we estimated is among the highest measured to date for IMBH-powered AGNs, implying that a typical AGN torus geometry might extend to the low-mass end. This work has implications for constraining the BH occupation fraction in dwarf galaxies using X-ray observations.

We examined the use of “edge of flood” habitats by larval silver carp during the extensive flooding that occurred in Pool 26 of the Upper Mississippi River near Alton, IL, USA and St. Louis, MO, USA during the summer of 2015. We captured over 12,700 individual fishes including eight taxa, over 12,000 of which (> 95%) were larval silver carp between 5 and 21 mm standard length. Peak catch rates occurred near the confluence of the Illinois and Mississippi rivers. These findings suggest that larval silver carp have an affinity for edge of the flood habitat and further study is needed to better understand how this affects the dynamics of this invasive species in the Mississippi River. The high catch rates observed at the confluence of the Illinois and Mississippi rivers suggests that the Illinois River is an important source of larval silver carp to the Upper Mississippi River.