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Background: Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a devastating disease of poultry and wild birds. ND is prevented by rigorous biocontainment and vaccination. One potential approach to prevent spread of the virus is production of birds that show innate resistance to NDV-caused disease. Induced pluripotent stem cell (iPSC) technology allows adult cells to be reprogrammed into an embryonic stem cell-like state capable of contributing to live offspring and passing on unique traits in a number of species. Recently, iPSC approaches have been successfully applied to avian cells. If chicken induced pluripotent stem cells (ciPSCs) are genetically or epigenetically modified to resist NDV infection, it may be possible to generate ND resistant poultry. There is limited information on the potential of ciPSCs to be infected by NDV, or the capacity of these cells to become resistant to infection. The aim of the present work was to assess the characteristics of the interaction between NDV and ciPSCs, and to develop a selection method that would increase tolerance of these cells to NDV-induced cellular damage. Results: Results showed that ciPSCs were permissive to infection with NDV, and susceptible to virus-mediated cell death. Since ciPSCs that survived infection demonstrated the ability to recover quickly, we devised a system to select surviving cells through multiple infection rounds with NDV. ciPSCs that sustained 9 consecutive infections had a statistically significant increase in survival (up to 36 times) compared to never-infected ciPSCs upon NDV infection (tolerant cells). Increased survival was not caused by a loss of permissiveness to NDV replication. RNA sequencing followed by enrichment pathway analysis showed that numerous metabolic pathways where differentially regulated between tolerant and never-infected ciPSCs. Conclusions: Results demonstrate that ciPSCs are permissive to NDV infection and become increasingly tolerant to NDV under selective pressure, indicating that this system could be applied to study mechanisms of cellular tolerance to NDV. [ABSTRACT FROM AUTHOR]

Background: Ehrlichiosis is a potentially fatal tick-borne disease that can progress to involve the central nervous system (CNS) (i.e., neuro-ehrlichiosis), particularly in cases where diagnosis and treatment are delayed. Despite a six-fold national increase in the incidence of ehrlichiosis over the past 20 years, recent data on the prevalence and manifestations of neuro-ehrlichiosis are lacking., Methods: We conducted a retrospective chart review of all patients tested for ehrlichiosis at University of North Carolina Health facilities between 2018 and 2021 and identified patients who met epidemiological criteria for ehrlichiosis as established by the Council of State and Territorial Epidemiologists and employed by the Centers for Disease Control and Prevention. We estimated the prevalence of neurological symptoms and described the spectrum of neurological manifestations in acute ehrlichiosis, documenting select patient cases in more detail in a case series., Results: Out of 55 patients with confirmed or probable ehrlichiosis, five patients (9.1%) had neurologic symptoms, which is notably lower than previous estimates. Neurological presentations were highly variable and included confusion, amnesia, seizures, focal neurological deficits mimicking ischemic vascular events, and an isolated cranial nerve palsy, though all patients had unremarkable neuroimaging at time of presentation. All but one patient had risk factors for severe ehrlichiosis (i.e., older age, immunosuppression)., Conclusions: Neuro-ehrlichiosis may lack unifying patterns in clinical presentation that would otherwise aid in diagnosis. Clinicians should maintain a high index of suspicion for neuro-ehrlichiosis in patients with acute febrile illness, diverse neurological symptoms, and negative neuroimaging in lone star tick endemic regions., (© 2024. The Author(s).)

Background: Despite decades of effort to reduce racial cancer disparities, Black people continue to die at higher rates from cancer than any other U.S. racial group. Because prevention is a key to the cost-effective and long-term control of cancer, the potential for cancer genetic counseling to play a central role in reducing racial cancer disparities is high. However, the benefits of genetic counseling are not equitable across race. Only 2% of genetic counselors self-identify as Black/African American, so most genetic counseling encounters with Black patients are racially discordant. Patients in racially discordant medical interactions tend to have poorer quality patient-provider communication and receive suboptimal clinical recommendations. One major factor that contributes to these healthcare disparities is racial bias. Drawing on findings from prior research, we hypothesize that genetic counselor providers' implicit racial prejudice will be associated negatively with the quality of patient-provider communication, while providers' explicit negative racial stereotypes will be associated negatively with the comprehensiveness of clinical discussions of cancer risk and genetic testing for Black (vs. White) patients., Methods: Using a convergent mixed methods research design, we will collect data from at least 15 genetic counseling providers, from two different institutions, and their 220 patients (approximately equal number of Black and White patients per provider) whose appointments are for a hereditary cancer condition. The data sources will include two provider surveys, two patient surveys, video- and/or audio-recordings of genetic counseling encounters, and medical chart reviews. The recorded cancer genetic counseling in-person and telehealth encounters will be analyzed both qualitatively and quantitatively to assess the quality of patient-provider communication and the comprehensiveness of clinical discussion. Those data will be linked to pre- and post-encounter survey data and data from medical chart reviews to test our hypotheses., Discussion: Findings from this multi-site study will highlight specific aspects of cancer genetic counseling encounters (patient-provider communication and clinical recommendations) that are directly associated with patient-centered outcomes (e.g., satisfaction, trust, genetic testing completion). Patient-provider communication and clinical recommendations are modifiable factors that can be integrated into current genetic counseling training curricula and thus can have immediate impact on genetic counseling training and practice., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Many factors influence young women's choice of contraceptive methods and where to source them, yet less is known about whether one of these choices (method or source) is prioritized and the relationship between these choices. This study qualitatively explored decision-making around contraceptive method and source choice among young women in Kenya., Methods: In August-September 2019, 30 in-depth interviews were conducted with women ages 18-24 who had used two or more contraceptive methods and resided in three counties: Nairobi, Mombasa or Migori. Participants were recruited from public and private health facilities and pharmacies. Interview guides captured information about decision-making processes for each contraceptive method the respondent had ever used. Responses were audio-recorded, transcribed, translated into English, coded, and analyzed thematically., Results: The majority of respondents knew which method they wanted to use prior to seeking it from a source. This was true for all types of methods that women ever used. Of the small number of respondents who selected their source first, most were in the post-partum period or experiencing side effects and sought counseling at a source before choosing a method., Conclusions: This study highlights the importance of providing young women with high quality counseling that provides full information about contraceptive options and addresses that young women's needs vary along the reproductive health continuum of care. This will ensure that young women have information to inform future contraceptive decision-making prior to seeking care., (© 2023. The Author(s).)

Background: A tax of one-Mexican peso per liter of sugar-sweetened beverage (SSB) came into effect in January 2014 in Mexico as a national health policy to tackle the high overweight and obesity prevalence. Previous studies have shown an overall reduction in SSB purchases after the tax implementation. However, it remains unknown whether and to what extent SSB consumers switched to cheaper taxed beverages, attenuating the potential effect of the policy. Our study's objective was to estimate changes in household purchases of taxed SSBs by tertiles of SSB prices (low, middle, and high) in urban areas after the SSB tax implementation in 2014., Methods: Based on purchase data for 2012-2015 from households living in 54 Mexican cities with a population > 50,000 inhabitants, we calculated unit-value SSB prices for the full period and sorted them on a monthly basis to create monthly price tertiles. We merged these price tertiles to household purchases and created average monthly ml/capita/day SSB purchases by price tertile at the city level. We assessed SSB purchase switching patterns before and after the tax implementation through price-tertile stratified linear models. The main variable in the models was a dummy indicator that allowed us to identify the pre-tax period (2012-13) and post-tax period (2014-15). We controlled our models for time trends and contextual economic variables., Results: In the regression adjusted models, we found a statistically significant purchase reduction ranging between 10.80 and 13.79 ml/capita/day (p-value < 0.001) across taxed beverages from the middle-price SSB after the tax implementation. We observed no statistically significant reductions in purchases of low-price SSBs and high-price SSBs., Conclusions: Our findings show purchase reductions in the middle-price SSBs, which represents ≈30% of the overall SSB purchases in urban Mexico. Future studies should be conducted to test if the redesign of the current the tax, by either doubling the tax amount or taxing sugar content, might reduce more effectively purchases across all SSBs., (© 2023. The Author(s).)

Background: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations., Methods: Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals., Results: Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation., Conclusions: Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development., (© 2022. The Author(s).)

Background: Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed., Methods: The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps-known locally as lesus-in children 6-18 months of age at a single site in rural western Uganda. Fifty mother-infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively., Results: Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0-1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2)., Conclusions: Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions., Trial Registration: ClinicalTrials.gov Identifier: NCT04102592, Registered 25 September 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT04102592., (© 2022. The Author(s).)

Background: Reducing red meat is a strategy to improve public health and mitigate climate change in the United States and other high-income countries. Policies requiring warnings on the front of red meat packages are a promising intervention to shift consumers towards healthier and more sustainable food choices. We aimed to explore participants' reactions to health and environmental warning messages about red meat., Methods: Between June and July 2020, we recruited a national convenience sample of US red meat consumers (n = 1,235; mean age 44 years) for an online survey. Participants were randomly assigned to one of four label conditions: no-label control, health warning, environment warning, and combined health and environment warning (both warnings shown side-by-side). Participants viewed three types of burritos (red meat [steak], chicken, and vegetarian) and selected their preferred item (primary outcome), the item they perceived to be most damaging to health, and the item they perceived to be most damaging to the environment (secondary outcomes). Participants then viewed their assigned warning on a series of other red meat products (no-label control participants were randomly re-assigned to one of the warning conditions) and rated the warnings on perceived message effectiveness, believability, negative emotions, perceived risk, attention, and learning something new. Finally, participants reported their intentions to reduce red meat consumption., Results: There were no significant differences in selection of the steak burrito between label conditions or in selection of the item most damaging to the environment. Those exposed to the health warning were more likely to select the steak burrito as most damaging to health compared to those exposed to other label conditions (health 73 %, combined 64 %, environment 60 %, no-label control 63 %, p < 0.05). The combined and health warnings elicited higher perceived message effectiveness ratings than the environment warning (combined mean 2.91, health 2.84, environment 2.61, p < 0.05)., Conclusions: Warnings did not have a significant effect on item preference in the choice experiment. However, combined and health warnings performed better than the environment warning across a variety of warning label reaction measures. More research will be needed to understand whether warnings elicit behavioral change in real-world environments., Trial Registration: Analyses and hypotheses were preregistered on https://aspredicted.org/ph7mb.pdf on 23 June 2020., (© 2021. The Author(s).)

Background: Transgender women in the United States (U.S.) experience a disproportionate burden of HIV infection and challenges to engagement in HIV prevention and care. This excess burden is driven by structural and economic inequities. Microeconomic interventions may be effective strategies for reducing HIV inequities for this population. However, few studies have explored transgender women's preferences for microeconomic interventions to address structural determinants of HIV vulnerability., Methods: We conducted individual interviews with 19 adult transgender women in 2 U.S. cities (Richmond, VA and St. Louis, MO) who reported one or more sexual risk behaviors and recent economic hardship related to employment/income, housing, or food security. Interviews were recorded, transcribed, and analyzed using thematic content analysis., Results: The majority (74%) of transgender women were racial/ethnic minorities with mean age of 26.3 years. 89% were currently economically vulnerable; and 23% were employed full-time. 37% reported living with HIV. Participants expressed strong support for unrestricted vouchers, with many expressing the need for funds to support gender-affirming interventions. Assistance with how to budget and save and support for job acquisition, career planning, and employment sustainment were also preferred, including access to non-stigmatizing employment. Visible transgender leadership, group empowerment, and small (rather than large) numbers of participants were considered important aspects of intervention design for transgender women, including outreach through existing transgender networks to facilitate inclusion. Incorporating HIV counseling and testing to reduce vulnerability to HIV was acceptable. However, transgender women enrolled in the study preferred that HIV not be the focus of an intervention., Conclusions: Flexible microeconomic interventions that support gender affirming interventions, improve financial literacy, and provide living-wage non-stigmatizing employment are desired by economically vulnerable transgender women. While not focused on HIV, such interventions have the potential to reduce the structural drivers of HIV vulnerability among transgender women., (© 2021. The Author(s).)

Background: Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999-2000) for individuals 20-49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates., Results: Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (- 0.30 [95% CI: - 0.36, - 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures., Conclusions: These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

Background: Consumption of non-nutritive sweeteners (NNS) is becoming increasingly more frequent, particularly in the context of obesity prevention policies. The aim of this study was to describe the consumption of NNS in an ongoing cohort of pre-schoolers (4-6-year-old) before the implementation of the Chilean Food Labelling and Advertising Law, identify sociodemographic and anthropometric characteristics associated with their consumption, and describe the main dietary sources of each NNS sub-type., Methods: In 959 low-medium income pre-schoolers from the Food and Environment Chilean Cohort (FECHIC), dietary data from a single 24-h recall was linked to NNS content information obtained from packaged foods (n = 12,233). The prevalence of NNS consumption was estimated by food source and characterized by child and maternal sociodemographic and anthropometric variables. Intakes and main dietary sources were described for the six most prevalent NNS in Chile: Sodium Cyclamate, Saccharin, Aspartame, Acesulfame Potassium, Sucralose, and Steviol glycosides., Results: Sixty-eight percent of the pre-schoolers consumed at least one source of NNS on the day of the dietary recall; most of them consumed NNS from foods and beverages (n = 532), while only 12% (n = 119) also consumed table-top sweeteners. The prevalence of NNS consumption was significantly higher among children whose mothers had a high educational level compared to children whose mothers did not complete high school (p < 0.05); however, it did not differ by any other variable studied. The highest intakes of NNS were observed for Aspartame [2.5 (1.4-3.7) mg/kg per consumer], followed by Sodium Cyclamate [1.6 (1.3-2.6) mg/kg per consumer] and Steviol glycosides [1.2 (0.2-2.1) mg/kg per consumer]. Beverages were the only food group that contributed to the intake of the six NNS studied, accounting for 22% of the overall intake of Saccharine and up to 99% of Aspartame intake., Conclusions: Before the implementation of the Food Labelling and Advertising Law, NNS consumption was highly prevalent among a cohort of low-middle income Chilean pre-schoolers. Continuous monitoring of NNS consumption is essential given potential food reformulation associated with the implementation of this set of obesity-prevention policies.

Background: Transgender women ("trans women"), particularly African-American and Latina trans women, have disproportionately high prevalence of HIV in the United States (U.S.). In order to decrease gender dysphoria and overcome discrimination, trans women affirm their gender through social and medical transition, often in contexts of economic hardship and sexual risk. This study qualitatively examined how gender-affirming behaviors enhance or diminish vulnerability to HIV in light of structural and economic barriers to gender transition., Methods: We conducted individual interviews with 19 adult trans women in two U.S. cities (Richmond, VA and St. Louis, MO) who reported one or more sexual risk behaviors and recent economic hardship related to employment/income, housing, or food security. Interviews were recorded, transcribed, and analyzed using thematic content analysis., Results: The majority (74%) of trans women were racial/ethnic minorities with mean age of 26.3 years. Gender-affirming behaviors varied with 58% of trans women having legally changed their name and gender marker; 79% having initiated hormone therapy; and 11% having not initiated any medical or legal changes. None had undertaken surgical changes. Findings suggested that the process of gender transitioning resulted in both increasing and decreasing HIV risk. The high need for gender affirmation by male sex partners contributed to trans women's exposure to sexual objectification, sexual risk behaviors, and conflicting interests in HIV prevention messaging. Loss of housing and employment due to transition along with the high costs of transition products and medical visits increased reliance on sex work and created new obstacles in accessing HIV services. Trans women experienced lower HIV risk as they acquired legal and medical transition services, reshaped interactions with sex partners, and received gender-affirming support by others, including health providers, employers, peers, and housing professionals. Sexual abstinence was viewed as a negative consequence of incomplete transition, although characterized as a period of low HIV risk., Conclusions: Structural and policy initiatives that promote safe gender transition and economic stability in trans women may play a critical role in reducing HIV in this population. Addressing the harmful pressures for U.S. trans women to conform to perceived feminine stereotypes may also serve an important role.

Background: Race and place intersect to produce location-based variation in disease distributions. We analyzed the geographic distribution of tuberculosis (TB) incidence in Michigan, USA to better understand the complex interplay between race and place, comparing patterns in Detroit, Wayne County and the state of Michigan as a whole., Methods: Using cross-sectional TB surveillance data from the Michigan Department of Health and Human Services, multivariable statistical models were developed to analyze the residence patterns of TB incidence from 2007 through 2012. Two-way interactions among the residence location and race of cases were assessed., Results: Overall, Detroit residents experienced 58% greater TB incidence than residents of Wayne County or the state of Michigan. Racial inequalities were less pronounced in Detroit compared to both Wayne County and the state of Michigan. Blacks in Detroit had 2.01 times greater TB incidence than Whites, while this inequality was 3.62 times more in Wayne County and 8.72 greater in the state of Michigan., Conclusion: Our results highlight how race and place interact to influence patterns of TB disease, and the ways in which this interaction is context dependent. TB elimination in the U.S. will require strategies that address the local social environment, as much as the physical environment.

Background: Conceptualizations of personality disorders (PD) are increasingly moving towards dimensional approaches. The definition and assessment of borderline personality disorder (BPD) in regard to changes in nosology are of great importance to theory and practice as well as consumers. We studied empirical connections between the traditional DSM-5 diagnostic criteria for BPD and Criteria A and B of the Alternative Model for Personality Disorders (AMPD)., Method: Raters of varied professional backgrounds possessing substantial knowledge of PDs ( N  = 20) characterized BPD criteria with the four domains of the Level of Personality Functioning Scale (LPFS) and 25 pathological personality trait facets. Mean AMPD values of each BPD criterion were used to support a nosological cross-walk of the individual BPD criteria and study various combinations of BPD criteria in their AMPD translation. The grand mean AMPD profile generated from the experts was compared to published BPD prototypes that used AMPD trait ratings and the DSM-5-III hybrid categorical-dimensional algorithm for BPD. Divergent comparisons with DSM-5-III algorithms for other PDs and other published PD prototypes were also examined., Results: Inter-rater reliability analyses showed generally robust agreement. The AMPD profile for BPD criteria rated by individual BPD criteria was not isomorphic with whole-person ratings of BPD, although they were highly correlated. Various AMPD profiles for BPD were generated from theoretically relevant but differing configurations of BPD criteria. These AMPD profiles were highly correlated and showed meaningful divergence from non-BPD DSM-5-III algorithms and other PD prototypes., Conclusions: Results show that traditional DSM BPD diagnosis reflects a common core of PD severity, largely composed of LPFS and the pathological traits of anxiousness, depressively, emotional lability, and impulsivity. Results confirm the traditional DSM criterion-based BPD diagnosis can be reliably cross-walked with the full AMPD scheme, and both approaches share substantial construct overlap. This relative equivalence suggests the vast clinical and research literatures associated with BPD may be brought forward with DSM-5-III diagnosis of BPD., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Background: Healthcare worker absenteeism is common in resource limited settings and contributes to poor quality of care in maternal and child health service delivery. There is a dearth of qualitative information on the scope, contributing factors, and impact of absenteeism in Kenyan healthcare facilities., Methods: In-depth semi-structured interviews were conducted between July 2015 and June 2016 with 20 healthcare providers in public and private healthcare facilities in Central and Western Kenya. Interviews were audio-recorded, transcribed, coded, and analyzed using an iterative thematic approach., Results: Half of providers reported that absenteeism occurs in both private and public health facilities. Absenteeism was most commonly characterized by providers arriving late or leaving early during scheduled work hours. The practice was attributed to institutional issues including: infrequent supervision, lack of professional consequences, limited accountability, and low wages. In some cases, healthcare workers were frequently absent because they held multiple positions at different health facilities. Provider absences result in increased patient wait times and may deter patients from seeking healthcare in the future., Conclusion: There is a significant need for policies and programs to reduce provider absenteeism in Kenya. Intervention approaches must be cognizant of the contributors to absenteeism which occur at the institutional level.

Background: The World Health Organization (WHO) International Classification of Diseases and Related Health Problems (ICD) is used globally by 194 WHO member nations. It is used for assigning clinical diagnoses, providing the framework for reporting public health data, and to inform the organization and reimbursement of health services. Guided by overarching principles of increasing clinical utility and global applicability, the 11th revision of the ICD proposes major changes that incorporate empirical advances since the previous revision in 1992. To test recommended changes in the Mental, Behavioral, and Neurodevelopmental Disorders chapter, multiple vignette-based case-controlled field studies have been conducted which examine clinicians' ability to accurately and consistently use the new guidelines and assess their overall clinical utility. This manuscript reports on the results from the study of the proposed ICD-11 guidelines for feeding and eating disorders (FEDs)., Method: Participants were 2288 mental health professionals registered with WHO's Global Clinical Practice Network. The study was conducted in Chinese, English, French, Japanese, and Spanish. Clinicians were randomly assigned to apply either the ICD-11 or ICD-10 diagnostic guidelines for FEDs to a pair of case vignettes designed to test specific clinical questions. Clinicians selected the diagnosis they thought was correct for each vignette, evaluated the presence of each essential feature of the selected diagnosis, and the clinical utility of the diagnostic guidelines., Results: The proposed ICD-11 diagnostic guidelines significantly improved accuracy for all FEDs tested relative to ICD-10 and attained higher clinical utility ratings; similar results were obtained across all five languages. The inclusion of binge eating disorder and avoidant-restrictive food intake disorder reduced the use of residual diagnoses. Areas needing further refinement were identified., Conclusions: The proposed ICD-11 diagnostic guidelines consistently outperformed ICD-10 in distinguishing cases of eating disorders and showed global applicability and appropriate clinical utility. These results suggest that the proposed ICD-11 guidelines for FEDs will help increase accuracy of public health data, improve clinical diagnosis, and enhance health service organization and provision. This is the first time in the revision of the ICD that data from large-scale, empirical research examining proposed guidelines is completed in time to inform the final diagnostic guidelines.

Introduction: Although growing, evidence on the impact, access, utility, effectiveness, and cost-benefit of obstetric ultrasound in resource-constrained settings is still somewhat limited. Hence, questions around the purpose and the intended benefit as well as potential challenges across various domains must be carefully reviewed prior to implementation and scale-up of obstetric ultrasound technology in low-and middle-income countries (LMICs)., Main Body: This narrative review discusses these issues for those trying to implement or scale-up ultrasound technology in LMICs. Issues addressed in this review include health personnel capacity, maintenance, cost, overuse and misuse of ultrasound, miscommunication between the providers and patients, patient diagnosis and care management, health outcomes, patient perceptions and concerns about fetal sex determination., Conclusion: As cost of obstetric ultrasound becomes more affordable in LMICs, it is essential to assess the benefits, trade-offs and potential drawbacks of large-scale implementation. Additionally, there is a need to more clearly identify the capabilities and the limitations of ultrasound, particularly within the context of limited training of providers, to ensure that the purpose for which an ultrasound is intended is actually feasible. We found evidence of obstetric uses of ultrasound improving patient management. However, there was evidence that ultrasound use is not associated with reducing maternal, perinatal or neonatal mortality. Patients in various studies reported to have both positive and negative perceptions and experiences related to ultrasound and lastly, illegal use of ultrasound for determining fetal sex was raised as a concern.

Background: We studied the effect of key development and expansion of an off-road multipurpose trail system in Minneapolis, Minnesota between 2000 and 2007 to understand whether infrastructure investments are associated with increases in commuting by bicycle., Methods: We used repeated measures regression on tract-level (N = 116 tracts) data to examine changes in bicycle commuting between 2000 and 2008-2012. We investigated: 1) trail proximity measured as distance from the trail system and 2) trail potential use measured as the proportion of commuting trips to destinations that might traverse the trail system. All analyses (performed 2015-2016) adjusted for tract-level sociodemographic covariates and contemporaneous cycling infrastructure changes (e.g., bicycle lanes)., Results: Tracts that were both closer to the new trail system and had a higher proportion of trips to destinations across the trail system experienced greater 10-year increases in commuting by bicycle., Conclusions: Proximity to off-road infrastructure and travel patterns are relevant to increased bicycle commuting, an important contributor to overall physical activity. Municipal investment in bicycle facilities, especially off-road trails that connect a city's population and its employment centers, is likely to lead to increases in commuting by bicycle.

Background: Cigarette smoking is an important risk factor for unhealthy dieting behaviors (UDBs) in youth. The role of alternative tobacco products and UDB engagement has yet to be examined empirically despite concerning trends in use. This study aimed to examine UDB prevalence in a U.S. geographic region-specific adolescent sample and associations with a variety of tobacco use behaviors and perceptions., Methods: Weighted data from the 2013 Virginia Youth Survey were analyzed ( n  = 6903). UDBs assessed included past 30-day fasting, diet pill use, and vomiting/laxative use. Tobacco-related items were ever and past 30-day cigarette smoking, past 30-day smokeless tobacco and cigar use, and the perception that smokers have more friends. UDB prevalence was recoded by the number of behaviors endorsed (0, 1, and 2+). Bivariate and multinomial regression models were used to examine associations between covariates and number of UDBs endorsed by gender., Results: Overall, nearly 16% engaged in at least one UDB. Fasting was most prevalent (14.2%) followed by vomiting/laxative (7.0%) and diet pill use (6.1%). Across gender, ever cigarette smoking, past 30-day cigar use, and the perception that smokers have more friends were positively associated with UDB engagement in relative isolation as well as in combination., Conclusions: Findings highlight the importance of tobacco-related factors for weight control behaviors and are the first to identify an association between UDB incidence and an alternative tobacco product, cigars. This work should inform prevention efforts for tobacco use and UDBs and underscores the need to address the use of any tobacco for weight control.

Background: The majority of glioblastomas have aberrant receptor tyrosine kinase (RTK)/RAS/phosphoinositide 3 kinase (PI3K) signaling pathways and malignant glioma cells are thought to be addicted to these signaling pathways for their survival and proliferation. However, recent studies suggest that monotherapies or inappropriate combination therapies using the molecular targeted drugs have limited efficacy possibly because of tumor heterogeneities, signaling redundancy and crosstalk in intracellular signaling network, indicating necessity of rationale and methods for efficient personalized combination treatments. Here, we evaluated the growth of colonies obtained from glioma tumor-initiating cells (GICs) derived from glioma sphere culture (GSC) in agarose and examined the effects of combination treatments on GICs using targeted drugs that affect the signaling pathways to which most glioma cells are addicted., Methods: Human GICs were cultured in agarose and treated with inhibitors of RTKs, non-receptor kinases or transcription factors. The colony number and volume were analyzed using a colony counter, and Chou-Talalay combination indices were evaluated. Autophagy and apoptosis were also analyzed. Phosphorylation of proteins was evaluated by reverse phase protein array and immunoblotting., Results: Increases of colony number and volume in agarose correlated with the Gompertz function. GICs showed diverse drug sensitivity, but inhibitions of RTK and RAF/MEK or PI3K by combinations such as EGFR inhibitor and MEK inhibitor, sorafenib and U0126, erlotinib and BKM120, and EGFR inhibitor and sorafenib showed synergy in different subtypes of GICs. Combination of erlotinib and sorafenib, synergistic in GSC11, induced apoptosis and autophagic cell death associated with suppressed Akt and ERK signaling pathways and decreased nuclear PKM2 and β-catenin in vitro, and tended to improve survival of nude mice bearing GSC11 brain tumor. Reverse phase protein array analysis of the synergistic treatment indicated involvement of not only MEK and PI3K signaling pathways but also others associated with glucose metabolism, fatty acid metabolism, gene transcription, histone methylation, iron transport, stress response, cell cycle, and apoptosis., Conclusion: Inhibiting RTK and RAF/MEK or PI3K could induce synergistic cytotoxicity but personalization is necessary. Examining colonies in agarose initiated by GICs from each patient may be useful for drug sensitivity testing in personalized cancer therapy.

Background: High-quality measurement is critical to advancing knowledge in any field. New fields, such as implementation science, are often beset with measurement gaps and poor quality instruments, a weakness that can be more easily addressed in light of systematic review findings. Although several reviews of quantitative instruments used in implementation science have been published, no studies have focused on instruments that measure implementation outcomes. Proctor and colleagues established a core set of implementation outcomes including: acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, sustainability (Adm Policy Ment Health Ment Health Serv Res 36:24-34, 2009). The Society for Implementation Research Collaboration (SIRC) Instrument Review Project employed an enhanced systematic review methodology (Implement Sci 2: 2015) to identify quantitative instruments of implementation outcomes relevant to mental or behavioral health settings., Methods: Full details of the enhanced systematic review methodology are available (Implement Sci 2: 2015). To increase the feasibility of the review, and consistent with the scope of SIRC, only instruments that were applicable to mental or behavioral health were included. The review, synthesis, and evaluation included the following: (1) a search protocol for the literature review of constructs; (2) the literature review of instruments using Web of Science and PsycINFO; and (3) data extraction and instrument quality ratings to inform knowledge synthesis. Our evidence-based assessment rating criteria quantified fundamental psychometric properties as well as a crude measure of usability. Two independent raters applied the evidence-based assessment rating criteria to each instrument to generate a quality profile., Results: We identified 104 instruments across eight constructs, with nearly half (n = 50) assessing acceptability and 19 identified for adoption, with all other implementation outcomes revealing fewer than 10 instruments. Only one instrument demonstrated at least minimal evidence for psychometric strength on all six of the evidence-based assessment criteria. The majority of instruments had no information regarding responsiveness or predictive validity., Conclusions: Implementation outcomes instrumentation is underdeveloped with respect to both the sheer number of available instruments and the psychometric quality of existing instruments. Until psychometric strength is established, the field will struggle to identify which implementation strategies work best, for which organizations, and under what conditions.

Background: Identification of psychometrically strong instruments for the field of implementation science is a high priority underscored in a recent National Institutes of Health working meeting (October 2013). Existing instrument reviews are limited in scope, methods, and findings. The Society for Implementation Research Collaboration Instrument Review Project's objectives address these limitations by identifying and applying a unique methodology to conduct a systematic and comprehensive review of quantitative instruments assessing constructs delineated in two of the field's most widely used frameworks, adopt a systematic search process (using standard search strings), and engage an international team of experts to assess the full range of psychometric criteria (reliability, construct and criterion validity). Although this work focuses on implementation of psychosocial interventions in mental health and health-care settings, the methodology and results will likely be useful across a broad spectrum of settings. This effort has culminated in a centralized online open-access repository of instruments depicting graphical head-to-head comparisons of their psychometric properties. This article describes the methodology and preliminary outcomes., Methods: The seven stages of the review, synthesis, and evaluation methodology include (1) setting the scope for the review, (2) identifying frameworks to organize and complete the review, (3) generating a search protocol for the literature review of constructs, (4) literature review of specific instruments, (5) development of an evidence-based assessment rating criteria, (6) data extraction and rating instrument quality by a task force of implementation experts to inform knowledge synthesis, and (7) the creation of a website repository., Results: To date, this multi-faceted and collaborative search and synthesis methodology has identified over 420 instruments related to 34 constructs (total 48 including subconstructs) that are relevant to implementation science. Despite numerous constructs having greater than 20 available instruments, which implies saturation, preliminary results suggest that few instruments stem from gold standard development procedures. We anticipate identifying few high-quality, psychometrically sound instruments once our evidence-based assessment rating criteria have been applied., Conclusions: The results of this methodology may enhance the rigor of implementation science evaluations by systematically facilitating access to psychometrically validated instruments and identifying where further instrument development is needed.

Background: Like many new fields, implementation science has become vulnerable to instrumentation issues that potentially threaten the strength of the developing knowledge base. For instance, many implementation studies report findings based on instruments that do not have established psychometric properties. This article aims to review six pressing instrumentation issues, discuss the impact of these issues on the field, and provide practical recommendations., Discussion: This debate centers on the impact of the following instrumentation issues: use of frameworks, theories, and models; role of psychometric properties; use of 'home-grown' and adapted instruments; choosing the most appropriate evaluation method and approach; practicality; and need for decision-making tools. Practical recommendations include: use of consensus definitions for key implementation constructs; reporting standards (e.g., regarding psychometrics, instrument adaptation); when to use multiple forms of observation and mixed methods; and accessing instrument repositories and decision aid tools., Summary: This debate provides an overview of six key instrumentation issues and offers several courses of action to limit the impact of these issues on the field. With careful attention to these issues, the field of implementation science can potentially move forward at the rapid pace that is respectfully demanded by community stakeholders.

Background: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model., Methods: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons., Results: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration., Conclusions: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

Background: Built environment research is dominated by cross-sectional designs, which are particularly vulnerable to residential self-selection bias resulting from health-related attitudes, neighborhood preferences, or other unmeasured characteristics related to both neighborhood choice and health-related outcomes., Methods: We used cohort data from the National Longitudinal Study of Adolescent Health (United States; Wave I, 1994-95; Wave III, 2001-02; n = 12,701) and a time-varying geographic information system. Longitudinal relationships between moderate to vigorous physical activity (MVPA) bouts and built and socioeconomic environment measures (landcover diversity, pay and public physical activity facilities per 10,000 population, street connectivity, median household income, and crime rate) from adolescence to young adulthood were estimated using random effects models (biased by unmeasured confounders) and fixed effects models (within-person estimator, which adjusts for unmeasured confounders that are stable over time)., Results: Random effects models yielded null associations except for negative crime-MVPA associations [coefficient (95% CI): -0.056 (-0.083, -0.029) in males, -0.061 (-0.090, -0.033) in females]. After controlling for measured and time invariant unmeasured characteristics using within-person estimators, MVPA was higher with greater physical activity pay facilities in males [coefficient (95% CI): 0.024 (0.006, 0.042)], and lower with higher crime rates in males [coefficient (95% CI): -0.107 (-0.140, -0.075)] and females [coefficient (95% CI): -0.046 (-0.083, -0.009)]. Other associations were null or in the counter-intuitive direction., Conclusions: Comparison of within-person estimates to estimates unadjusted for unmeasured characteristics suggest that residential self-selection can bias associations toward the null, as opposed to its typical characterization as a positive confounder. Differential environment-MVPA associations by residential relocation suggest that studies examining changes following residential relocation may be vulnerable to selection bias. The authors discuss complexities of adjusting for residential self-selection and residential relocation, particularly during the adolescent to young adult transition.