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The critical mechanism to restart zygote metabolism and prevent polyspermy during fertilization is the intracellular Ca2+ increase. All of the signaling molecules leading to the Ca2+ rise are not fully known in any species. In the sea star Patiria miniata, SFK1, SFK3, and PLCγ participate in this fertilization Ca2+ increase. These proteins share common regulatory features, including signaling via tyrosine phosphorylation and their SH2 domains. In this study, we explore two different bioinformatic strategies to identify transcripts in the Patiria miniata mature egg transcriptome (Accession PRJNA398668) that code for proteins possessing an SH2 domain. The first identified the longest open reading frame for each transcript and then utilized similarity searching tools to provide identities for each transcript. The second, novel, method involved a six-frame translation of the entire transcriptome to identify SH2 domain-containing proteins. The identified transcripts were aligned against the NCBI non-redundant database and the SwissProt database. Eighty-two transcripts that encoded SH2 domains were identified. Of these, 33 were only found using the novel method. This work furthers research into egg activation by providing possible target proteins for future experiments and a novel method for identifying specific proteins of interest within a de novo transcriptome.

To estimate the water use of vegetable and row crops, crop coefficients were developed using portable Bowen ratio instruments that were constructed and tested against lysimeters. These instruments measured evapotranspiration (ET) in fields of vegetable and row crops at various developmental stages. The crop coefficient was calculated at different percentages of ground cover using a direct ratio between the ET of the crop and that of a reference grass, which was calculated using meteorological data calculated from local CIMIS weather stations. The crop coefficients for most of the crops increased as the percentage of ground cover increased.

Abstract Background Although the cost of implementing evidence-based interventions (EBIs) is a key determinant of adoption, lack of cost information is widespread. We previously evaluated the cost of preparing to implement Family Check-Up 4 Health (FCU4Health), an individually tailored, evidence-based parenting program that takes a whole child approach, with effects on both behavioral health and health behavior outcomes, in primary care settings. This study estimates the cost of implementation, including preparation. Methods We assessed the cost of FCU4Health across the preparation and implementation phases spanning 32 months and 1 week (October 1, 2016–June 13, 2019) in a type 2 hybrid effectiveness-implementation study. This family-level randomized controlled trial took place in Arizona with n = 113 predominantly low-income, Latino families with children ages > 5.5 to

This research article seeks to understand how the cultural context of tuberculosis (TB) care in Ukraine influences healthcare workers’ perception of their patients and the choices they make in offering TB treatment. Specifically, we aim to explore healthcare workers’ predilection towards inpatient treatment of TB in Ukraine in lieu of other, evidence-based treatment approaches. Based on qualitative research with TB care providers in Ukraine, we argue that a preference for inpatient treatment instead of the standard outpatient regimen is rooted in the care workers’ assessment of the patient’s desire to get well. In other words, the preferred treatment modality is not based on any biological characteristic of TB infection; instead, it is based on the perceived strengths and weaknesses of patients’ psychology.

Abstract Bi‐allelic variants in Iron–Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early‐onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra‐rare bi‐allelic NFU1 missense variants associated with a spectrum of early‐onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1‐related phenotypic continuum.

The objective of this study was to observe the response of the bird cherry oat aphid, Rhopalosiphum padi (Linnaeus, 1758) to field rate equivalents of insecticides, by using bioassays of vials coated with the pyrethroid, λ-cyhalothrin. The results from the geographically separated Irish R. padi colonies indicated a susceptible response, which was a similar finding to the UK which showed sensitivity in this species of cereal aphids. Monitoring the susceptibility status of aphids using bioassays gives information regarding developments of any tolerance, which could be a precursor, or resistance against the target chemical insecticide, which is an important integrated pest management tool.

Background: The burden of cardiovascular disease (CVD) is particularly high in several US states, which include the state of Michigan. Hypertension and smoking are two major risk factors for mortality due to CVD. Rural Michigan is disproportionally affected by CVD and by primary care shortages. The Healthy Hearts for Michigan (HH4M) study aims to promote hypertension management and smoking cessation through practice facilitation and quality improvement efforts and is part of the multi-state EvidenceNOW: Building State Capacity initiative to provide external support to primary care practices to improve care delivery. Methods: Primary care practices in rural and underserved areas of Michigan were recruited to join HH4M, a pragmatic, single-arm hybrid Type 2 effectiveness-implementation study during which practice facilitation was delivered at the practice level for 12 months, followed by a 3-month maintenance period. Results: Fifty-four practices were enrolled over a 12-month recruitment period. At baseline, the mean proportion (standard deviation) of patients at the practice level meeting the clinical quality measures were: blood pressure, 0.72 (0.12); tobacco screening, 0.80 (0.30); tobacco cessation intervention, 0.57 (0.28); tobacco screening and cessation intervention: 0.78 (0.26). Conclusion: This three-year research program will evaluate the ability of rural and medically underserved primary care practices to implement the quality improvement model by identifying drivers of and barriers to sustainable implementation, and test whether the model improves (a) blood pressure control and (b) tobacco use screening and cessation.

Abstract Background In 2016, the US state of North Carolina (NC) legalized syringe services programs (SSPs), providing limited immunity from misdemeanor syringe possession when law enforcement is presented documentation that syringes were obtained from an SSP. This study explores the law enforcement interactions experienced by SSP participants since the enactment of this law. Methods This study used a convergent, mixed-methods design consisting of structured surveys and semi-structured interviews with SSP participants in seven NC counties. Survey and interview data were collected simultaneously between January and November 2019. This survey was designed to capture demographics, characteristics of drug use, SSP services used, and past-year negative experiences with law enforcement (officer did not recognize SSP card, did not believe SSP card belonged to participant, confiscated SSP card, confiscated syringes, or arrested participant for possessing syringes). Semi-structured interviews explored lived experiences with and perspectives on the same topics covered in the survey. Results A total of 414 SSP participants completed the survey (45% male, 54% female, 1% transgender or non-binary; 65% White, 22% Black, 5% American Indian/Alaskan Native, 8% some other racial identity). 212 participants (51.2%) reported at least one past-year negative experience with law enforcement. Chi-square testing suggests that Black respondents were more likely to report having experienced law enforcement doubt their SSP card belonged to them. Interview data indicate that law enforcement practices vary greatly across counties, and that negative and/or coercive interactions reduce expectations among SSP participants that they will be afforded the protections granted by NC law. Conclusion Despite laws which protect SSP participants from charges, negative law enforcement responses to syringe possession are still widely reported. Evidence-based policy interventions to reduce fatal overdose are undermined by these experiences. Our findings suggest NC residents, and officers who enforce these laws, may benefit from clarification as to what is required of the documents which identify participants of registered SSPs where they may legally obtain syringes. Likewise, more thorough trainings on NC’s syringe law for law enforcement officers may be merited. Further research is needed to assess geographic differences in SSP participants’ law enforcement interactions across race and gender.

BackgroundAdolescence is a vulnerable developmental period, characterized by high rates of mental health concerns, yet few adolescents receive treatment. Public libraries support adolescents by providing them with access to teen programming, technological resources, and have recently been providing mental health services. Digital mental health (DMH) services may help libraries provide scalable mental health solutions for their adolescent patrons and could be well positioned to address the mental health needs of historically underrepresented racial and ethnic (HURE) adolescents; however, little research has been conducted on the compatibility of DMH services with adolescent patron mental health needs or resource needs of library workers supporting them.MethodsThe research team formed a partnership with a public library, which serves a large HURE adolescent population. We conducted needs assessment and implementation readiness interviews with 17 library workers, including leadership, librarians, and workers with specialized areas of practice. Interview questions focused on library infrastructure, as well as library needs and preferences around the design and implementation of DMH services for adolescents. We used the Consolidated Framework for Implementation Research as guiding implementation determinant framework to code and analyze the interview transcripts.ResultsOur findings revealed library workers play an important role in guiding patrons to desired resources and share a goal of implementing adolescent DMH resources into the library and elevating marginalized adolescents’ voices. Existing library resources, such as the library's role as a safe space for adolescents in the community, close relationships with external and community organizations, and availability of no-cost technological resources, could help facilitate the implementation of DMH services. Barriers related to community buy-in, mental health stigma, and library worker confidence in supporting adolescent mental health could affect service implementation.ConclusionsOur findings suggest public libraries are highly promising settings to deploy DMH services for adolescents. We identified important determinants that may impact the implementation of DMH services in public library settings. Special considerations are needed to design services to meet the mental health needs of HURE adolescent populations and those adolescents’ most experiencing health inequities.

Abstract Background The spatial ventricular gradient (SVG) is a vectorcardiographic measurement that reflects cardiac loading conditions via electromechanical coupling. Objectives We hypothesized that the SVG is correlated with right ventricular (RV) strain and is prognostic of adverse events in patients with acute pulmonary embolism (PE). Methods Retrospective, single‐center study of patients with acute PE. Electrocardiogram (ECG), imaging, and outcome data were obtained. SVG components were regressed on tricuspid annular plane systolic excursion (TAPSE), qualitative RV dysfunction, and RV/left ventricular (LV) ratio. Odds of adverse outcomes (30‐day mortality, vasopressor requirement, or advanced therapy) after PE were regressed on demographics, RV/LV ratios, traditional ECG signs of RV dysfunction, and SVG components using a logit model. Results ECGs from 317 patients (48% male, age 63.1 ± 16.6 years) with acute PE were analyzed; 36 patients (11.4%) experienced an adverse event. Worse RV hypokinesis, larger RV/LV ratio, and smaller TAPSE were associated with smaller SVG X and Y components, larger SVG Z components, and smaller SVG vector magnitude (p

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

Abstract Background This article provides a generalizable method, rooted in co-design and stakeholder engagement, to identify, specify, and prioritize implementation strategies. To illustrate this method, we present a case example focused on identifying strategies to promote pediatric hypertension (pHTN) Clinical Practice Guideline (CPG) implementation in community health center-based primary care practices that involved meaningful engagement of pediatric clinicians, clinic staff, and patients/caregivers. This example was chosen based on the difficulty clinicians and organizations experience in implementing the pHTN CPG, as evidenced by low rates of guideline-adherent pHTN diagnosis and treatment. Methods We convened a Stakeholder Advisory Panel (SAP), comprising 6 pediatricians and 5 academic partners, for 8 meetings (~12 h total) to rigorously identify determinants of pHTN CPG adherence and to ultimately develop a testable multilevel, multicomponent implementation strategy. Our approach expanded upon the Expert Recommendations for Implementation Change (ERIC) protocol by incorporating a modified Delphi approach, user-centered design methods, and the Implementation Research Logic Model (IRLM). At the recommendation of our SAP, we gathered further input from youth with or at-risk for pHTN and their caregivers, as well as clinic staff who would be responsible for carrying out facets of the implementation strategy. Results First, the SAP identified 17 determinants, and 18 discrete strategies were prioritized for inclusion. The strategies primarily targeted determinants in the domains of intervention characteristics, inner setting, and characteristics of the implementers. Based on SAP ratings of strategy effectiveness, feasibility, and priority, three tiers of strategies emerged, with 7 strategies comprising the top tier implementation strategy package. Next, input from caregivers and clinic staff confirmed the feasibility and acceptability of the implementation strategies and provided further detail in the definition and specification of those strategies. Conclusions This method—an adaptation of the ERIC protocol—provided a pragmatic structure to work with stakeholders to efficiently identify implementation strategies, particularly when supplemented with user-centered design activities and the intuitive organizing framework of the IRLM. This generalizable method can help researchers identify and prioritize strategies that align with the implementation context with an increased likelihood of adoption and sustained use.

Background: A ‘terrible triad injury of the elbow’ (TTIE) refers to an injury pattern involving posterior dislocation of the ulnohumeral joint, fracture of the radial head, and fracture of the coronoid process of the ulna. It is a complex injury to the elbow joint and can result in long-term elbow instability, pain, stiffness, and arthritis. In specific cases, it may be treated conservatively, but in most circumstances, surgical stabilization is advised.The ‘drop sign’ is an objective static radiographically measured ulnohumeral distance of ≥4 mm seen intraoperatively and postoperatively. Although controversial, it may portend postoperative instability and arthritis. The senior author repairs these injuries in a standardized fashion through a modified Boyd rather than a lateral approach. Our aim was to assess the number of cases demonstrating an intraoperative drop sign after surgical treatment of a TTIE with this approach. Methods: We retrospectively analyzed 22 consecutive patients with 23 acute TTIEs. These injuries were treated by a single surgeon using a modified Boyd (posterior) approach to the elbow. Intraoperative image intensifier x-rays were analyzed by the two authors to assess for a ‘drop sign’. Results: None of the 23 cases had ‘drop signs’ on intraoperative imaging after stabilization. No patient has redislocated, underwent reoperation, or had symptoms of instability at follow-up. Conclusion: None of our patient cohort had an intraoperative ‘drop sign’ after standardized stabilization for a TTIE injury using a modified Boyd approach.

This paper presents the state-of-the-art technologies and development trends of wind turbine drivetrains – the system that converts kinetic energy of the wind to electrical energy – in different stages of their life cycle: design, manufacturing, installation, operation, lifetime extension, decommissioning and recycling. Offshore development and digitalization are also a focal point in this study. Drivetrain in this context includes the whole power conversion system: main bearing, shafts, gearbox, generator and power converter. The main aim of this article is to review the drivetrain technology development as well as to identify future challenges and research gaps. The main challenges in drivetrain research identified in this paper include drivetrain dynamic responses in large or floating turbines, aerodynamic and farm control effects, use of rare-earth material in generators, improving reliability through prognostics, and use of advances in digitalization. These challenges illustrate the multidisciplinary aspect of wind turbine drivetrains, which emphasizes the need for more interdisciplinary research and collaboration.

Abstract Objectives Unpredictable fluctuations in the illicit drug market increase overdose risk. Drug checking, or the use of technology to provide insight into the contents of illicit drug products, is an overdose prevention strategy with an emerging evidence base. The use of portable spectrometry devices to provide point-of-service analysis of the contents of illicit drugs been adopted by harm reduction organizations internationally but is only emerging in the United States. This study aimed to identify barriers and facilitators of implementing drug checking services with spectrometry devices in an urban harm reduction organization and syringe service program serving economically marginalized people who use drugs in Boston, Massachusetts (USA). Methods In-vivo observations and semi-structured interviews with harm reduction staff and participants were conducted between March 2019 and December 2020. We used the consolidated framework for implementation research to identify implementation barriers and facilitators. Results This implementation effort was facilitated by the organization’s shared culture of harm reduction—which fostered shared implementation goals and beliefs about the intervention among staff persons—its horizontal organizational structure, strong identification with the organization among staff, and strong relationships with external funders. Barriers to implementation included the technological complexity of the advanced spectroscopy devices utilized for drug checking. Program staff indicated that commercially available spectroscopy devices are powerful but not always well-suited for drug checking efforts, describing their technological capacities as “the Bronze Age of Drug Checking.” Other significant barriers include the legal ambiguity of drug checking services, disruptive and oppositional police activity, and the responses and programmatic changes demanded by the COVID-19 pandemic. Conclusions For harm reduction organizations to be successful in efforts to implement and scale drug checking services, these critical barriers—especially regressive policing policies and prohibitive costs—need to be addressed. Future research on the impact of policy changes to reduce the criminalization of substance use or to provide explicit legal frameworks for the provision of this and other harm reduction services may be merited.

Airborne differential absorption lidar (DIAL) offers a uniquely capable solution to the problem of measuring water vapor (WV) with high precision, accuracy, and resolution throughout the troposphere and lower stratosphere. The High Altitude Lidar Observatory (HALO) airborne WV DIAL was recently developed at NASA Langley Research Center and was first deployed in 2019. It uses four wavelengths near 935 nm to achieve sensitivity over a wide dynamic range and simultaneously employs 1064 nm backscatter and 532 nm high-spectral-resolution lidar (HSRL) measurements for aerosol and cloud profiling. A key component of the WV retrieval framework is flexibly trading resolution for precision to achieve optimal datasets for scientific objectives across scales. An approach to retrieving WV in the lowest few hundred meters of the atmosphere using the strong surface return signal is also presented. The five maiden flights of the HALO WV DIAL spanned the tropics through midlatitudes with a wide range of atmospheric conditions, but opportunities for validation were sparse. Comparisons to dropsonde WV profiles were qualitatively in good agreement, though statistical analysis was impossible due to systematic error in the dropsonde measurements. Comparison of HALO to in situ WV measurements aboard the aircraft showed no substantial bias across 3 orders of magnitude, despite variance (R2=0.66) that may be largely attributed to spatiotemporal variability. Precipitable water vapor measurements from the spaceborne sounders AIRS and IASI compared very well to HALO with R2>0.96 over ocean.

The Medical Library Association (MLA) has defined 7 domain hubs aligning to different areas of information professional practice. To assess the extent to which content in the Journal of the Medical Library Association (JMLA) is reflective of these domains, we analyzed the magnitude of JMLA articles aligning to each domain hub over the last 10 years. Bibliographic records for 453 articles published in JMLA from 2010 to 2019 were downloaded from Web of Science and screened using Covidence software. Thirteen articles were excluded during the title and abstract review because they failed to meet the inclusion criteria, resulting in articles included in this review. The title and abstract of each article were screened by two reviewers, each of whom assigned the article up to two tags corresponding to MLA domain hubs (i.e., information services, information management, education, professionalism and leadership, innovation and research practice, clinical support, and health equity & global health). These results inform the MLA community about our strengths in health information professional practice as reflected by articles published in JMLA.

Background Parkinson's disease is a degenerative neurological disorder that can cause both motor and nonmotor symptoms. Motor symptoms are associated with increasing the patient's falls risk. Shoulder arthroplasty surgery in this patient cohort is associated with more complications than non-Parkinsonian patients. We sought to identify any increase in complications associated with this patient cohort and any surgical considerations that ought to be taken in light of their disease process. Methods We performed a systematic review of articles using PubMed, MEDLINE, Cochrane Central, and Google Scholar. All studies which included any shoulder arthroplasty surgery for patients with Parkinson's disease were included. Results Complication rates were higher in patients with Parkinson's disease than in the normal arthroplasty cohort in all studies. There was significant heterogeneity between all 8 studies included in the systematic review. Complication rates ranged from 26% to 100%. Complications included subluxation, loosening, malunion, nonunion, scapular notching, stiffness, fracture, baseplate failure, dislocation, and infection. Reoperation rates ranged from 5% to 29%. Conclusion Compared to patients without Parkinson's disease undergoing shoulder arthroplasty, patients with Parkinson's disease achieved similar reductions in pain but inferior clinical function. The range of movement was less predictable, and complication rates were significantly higher in Parkinson's disease patients. This study will aid the surgeon and patient regarding surgical intervention, informed consent, and allow the surgeon to anticipate potential complications of shoulder arthroplasty in this patient cohort.

IMPORTANCE AND OBJECTIVES:. The primary objective of this study was to determine whether expression of the multifunctional and adherens junction-regulating protein, annexin A2 (A2), is altered following cardiopulmonary bypass (CPB). A secondary objective was to determine whether depletion of A2 is associated with post-CPB organ dysfunction in children. DESIGN:. In a prospective, observational study conducted over a 1-year period in children undergoing cardiac surgery requiring CPB, we analyzed A2 expression in peripheral blood mononuclear cells at different time points. We then assessed the relationship of A2 expression with organ function at each time point in the early postoperative period. SETTING:. Twenty-three-bed mixed PICU in a tertiary academic center. PARTICIPANTS:. Patients 1 month to 18 years old undergoing cardiac surgery requiring CPB. MEAN OUTCOME MEASUREMENTS AND RESULTS:. We analyzed A2 expression in 22 enrolled subjects (n = 9, 1–23 mo old; n = 13, 2–18 yr old) and found a proteolysis-mediated decline in intact A2 immediately after bypass (p = 0.0009), reaching a median of 4% of baseline at 6 hours after bypass (p < 0.0001), and recovery by postoperative day 1. The degree of A2 depletion immediately after bypass in 1–23-month-olds correlated strongly with the extent of organ dysfunction, as measured by PICU admission Vasoactive-Ventilation-Renal (p = 0.004) and PEdiatric Logistic Organ Dysfunction-2 (p = 0.039) scores on postoperative day 1. A2 depletion immediately after bypass also correlated with more protracted requirement for both respiratory support (p = 0.007) and invasive ventilation (p = 0.013) in the 1–23-month-olds. CONCLUSIONS AND RELEVANCE:. The degree of depletion of A2 following CPB correlates with more severe organ dysfunction, especially acute respiratory compromise in children under 2 years. These findings suggest that loss of A2 may contribute to pulmonary microvascular leak in young children following CPB.

Abstract Introduction Currently, one of the commonly used methods for disseminating electronic health record (EHR)-based phenotype algorithms is providing a narrative description of the algorithm logic, often accompanied by flowcharts. A challenge with this mode of dissemination is the potential for under-specification in the algorithm definition, which leads to ambiguity and vagueness. Methods This study examines incidents of under-specification that occurred during the implementation of 34 narrative phenotyping algorithms in the electronic Medical Record and Genomics (eMERGE) network. We reviewed the online communication history between algorithm developers and implementers within the Phenotype Knowledge Base (PheKB) platform, where questions could be raised and answered regarding the intended implementation of a phenotype algorithm. Results We developed a taxonomy of under-specification categories via an iterative review process between two groups of annotators. Under-specifications that lead to ambiguity and vagueness were consistently found across narrative phenotype algorithms developed by all involved eMERGE sites. Discussion and conclusion Our findings highlight that under-specification is an impediment to the accuracy and efficiency of the implementation of current narrative phenotyping algorithms, and we propose approaches for mitigating these issues and improved methods for disseminating EHR phenotyping algorithms.

Residents of socioeconomically disadvantaged neighbourhoods have higher rates of overweight and obesity and chronic disease than their counterparts from advantaged neighbourhoods. This study assessed whether associations between neighbourhood disadvantage and measured body mass index (BMI) and waist circumference, are accounted for by obesogenic environments (i.e., residential distance to the Central Business District [CBD], supermarket availability, access to walkable destinations). The study used 2017-18 National Health Survey data for working-aged adults (aged ≥18 years, n = 9,367) residing in 3,454 neighbourhoods across Australia's state and territory capital cities. In five of eight cities (i.e., Sydney, Melbourne, Brisbane, Adelaide, and Perth) residents of disadvantaged neighbourhoods had significantly higher BMI and a larger waist circumference than residents of more advantaged areas. There was no association between neighbourhood disadvantage and body size in Hobart, Darwin, and Canberra. Associations between neighbourhood disadvantage and body size were partially explained by neighbourhood differences in distance to the CBD but not supermarket availability or walkable amenities. The results of this study point to the role of urban design and city planning as mechanisms for addressing social and economic inequities in Australia's capital cities, and as solutions to this country's overweight and obesity epidemic and associated rising rates of chronic disease.

Three-dimensional (3D) cell culture models can help bridge the gap between in vitro cell cultures and in vivo responses by more accurately simulating the natural in vivo environment, shape, tissue stiffness, stressors, gradients and cellular response while avoiding the costs and ethical concerns associated with animal models. The inclusion of the third dimension in 3D cell culture influences the spatial organization of cell surface receptors that interact with other cells and imposes physical restrictions on cells in compared to Two-dimensional (2D) cell cultures. Spheroids’ distinctive cyto-architecture mimics in vivo cellular structure, gene expression, metabolism, proliferation, oxygenation, nutrition absorption, waste excretion, and drug uptake while preserving cell–extracellular matrix (ECM) connections and communication, hence influencing molecular processes and cellular phenotypes. This protocol describes the in vitro generation of tumourspheroids using the low attachment plate, hanging drop plate, and cellusponge natural scaffold based methods. The expected results from these protocols confirmed the ability of all these methods to create uniform tumourspheres.

Abstract Background Large interindividual variations have been reported in chemotherapy‐induced toxicities. Little is known whether racial disparities exist in neutropenia associated with taxanes. Methods Patients with a diagnosis of primary cancer who underwent chemotherapy with taxanes were identified from Vanderbilt University Medical Center's Synthetic Derivative. Multinomial regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of neutropenia associated with race, with adjustments for demographic variables, baseline neutrophil count, chemotherapy‐related information, prior treatments, and cancer site. Results A total of 3492 patients were included in the study. Compared with White patients, grade 2 or higher neutropenia was more frequently recorded among Black patients who received taxanes overall (42.2% vs. 32.7%, p

Abstract Four studies involving 2552 White American participants were conducted to investigate bias based on the race-based phenotype of hair texture. Specifically, we probed the existence and magnitude of bias in favor of Eurocentric (straight) over Afrocentric (curly) hair and its specificity in predicting responses to a legal decision involving the phenotype. Study 1 revealed an implicit preference, measured by an Implicit Association Test (IAT), favoring Eurocentric over Afrocentric hair texture among White Americans. This effect was not reducible to a Black/White implicit race attitude nor to mere perceptual preference favoring straight over curly hair. In Study 2, the phenotype (hair) IAT significantly and uniquely predicted expressions of support in response to an actual legal case that involved discrimination on the basis of Afrocentric hair texture. Beyond replicating this result, Studies 3 and 4 (the latter preregistered) provided further, and even more stringent, evidence for incremental predictive validity: in both studies, the phenotype IAT was associated with support for a Black plaintiff above and beyond the effects of two parallel explicit scales and, additionally, a race attitude IAT. Overall, these studies support the idea that race bias may be uniquely detected by examining implicit attitudes elicited by group-based phenotypicality, such as hair texture. Moreover, the present results inform theoretical investigations of the correspondence principle in the context of implicit social cognition: they suggest that tailoring IATs to index specific aspects of an attitude object (e.g., by decomposition of phenotypes) can improve prediction of intergroup behavior.

Abstract Recently, a novel knowledge bank (KB) approach to predict outcomes of individual patients with acute myeloid leukemia (AML) was developed using unbiased machine learning. To validate its prognostic value, we analyzed 1612 adults with de novo AML treated on Cancer and Leukemia Group B front-line trials who had pretreatment clinical, cytogenetics, and mutation data on 81 leukemia/cancer-associated genes available. We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate the predictive values of the KB algorithm and other risk classifications. The KB algorithm predicted 3-year overall survival (OS) probability in the entire patient cohort (AUCKB = 0.799), and both younger (

Objective: To assess the outcome of empirical therapeutic interventions for synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Methods: The clinical features and treatment outcomes of a cohort of 21 patients diagnosed with SAPHO in Western Australia were reviewed retrospectively. Results: All 21 patients met published diagnostic criteria; 20 (95%) were Caucasian, and the median age was 47 years. The median follow-up was 6 years (range, 2 to 32 years). Three patients (14%) received no treatment; 18 (86%) required conventional synthetic disease-modifying antirheumatic drug (DMARDs). Thirteen (62%) had an initial good response to methotrexate; 8 relapsed and progressed to biologic DMARDs (bDMARDs) during a period of 14 years. Of the 13 recipients on a tumor necrosis factor inhibitor, 11 (85%) continued treatment for a median of 4 years (range, 1 to 14 years), whereas none of 3 recipients of interleukin 17/23 continued treatment (median, 4 months). Higher Physician Global Assessment scores (better outcomes) were observed in bDMARD recipients (mean, 7.06±2.24 [SD]) compared with non-bDMARD recipients (mean, 5.63±2.50; P=.1672) after a median of 3 years of therapy. Conclusion: This study describes the broad range of clinical manifestations in SAPHO, variable courses over time, and inconsistent outcomes with diverse empirical therapies. Moderately good long-term treatment outcomes were observed in most recipients of tumor necrosis factor inhibitor. Poorer outcomes were observed with bisphosphonates and interleukin 17/23 axis inhibitors; however, low numbers preclude robust comparison. Suboptimal treatment may be associated with poorer clinical outcomes and greater skeletal damage. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12619000445178

Accumulating evidences point to a discrepancy in the epigenetic behaviour of transgenes and endogenous genes. Here, via characterization of mutants impaired in histone demethylases JMJ14 and IBM1, the authors show that transgenes and endogenous genes are regulated by different epigenetic mechanisms in Arabidopsis.

Ce(IV) organometallic compounds are rare due to Ce(IV) being a powerful oxidant. Herein, the authors explore the covalency of a pair of organocerium complexes bearing a Ce(IV)-C(aryl) bond and examine their structure by NMR spectroscopy, X-ray diffraction analysis, and computational calculations.

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor. These cells have a highly complex karyotype with extensive chromothripsis. 2XSB cells show robust invasive 3-dimensional and clonogenic culture capability and form solid tumors when xenografted into immunodeficient mice. High-density single nucleotide polymorphism array and whole exome sequencing analyses indicate that, unlike NF1-associated MPNSTs, 2XSB cells have intact, functional NF1 alleles with no evidence of mutations in genes encoding components of Polycomb Repressor Complex 2. However, mutations in other genes implicated in MPNST pathogenesis were identified in 2XSB cells including homozygous deletion of CDKN2A and mutations in TP53 and PTEN. We also identified mutations in genes not previously associated with MPNSTs but associated with the pathogenesis of other human cancers. These include DNMT1, NUMA1, NTRK1, PDE11A, CSMD3, LRP5 and ACTL9. This sporadic MPNST-derived cell line provides a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs.

Abstract Background Residential environment features such as availability of supermarkets may shape dietary behaviour and thus overweight and obesity. This relationship may not be consistent between cities. This Australian national-level study examined: 1) the relationship between supermarket availability and body size; and 2) whether this relationship varied by capital city. Methods This study used 2017–18 Australian National Health Survey data including individual-level socio-demographic information (age, sex, country of birth, education, occupation, household income), and measured body size (height and weight to derive body mass index [BMI], and waist circumference [WC]). Objectively-expressed measures of residential environments included: counts of supermarkets (major chain outlets), counts of amenities (representing walkable destinations including essential services, recreation, and entertainment), and area of public open space - each expressed within road-network buffers at 1000 m and 1500 m; population density (1km2 grid cells); and neighbourhood disadvantage (Index of Relative Socioeconomic Disadvantage) expressed within Statistical Area Level 1 units. Data for adult respondents ≥18 years residing in each of Australia’s state and territory capital cities (n = 9649) were used in multilevel models to estimate associations between supermarket availability and body size sequentially accounting for individual and other environment measures. An interaction term estimated city-specific differences in associations between supermarket availability and body size. Models were consequently repeated stratified by city. Results Body size (BMI and WC) and supermarket availability varied between cities. Initial inverse associations between supermarket availability and body size (BMI and WC) were attenuated to null with inclusion of all covariates, except for BMI in the 1000 m buffer model (beta = − 0.148, 95%CI -0.27, − 0.01, p = 0.025). In stratified analyses, the strengths of associations varied between cities, remaining statistically significant only for some cities (BMI: Melbourne, Brisbane Hobart; WC: Brisbane, Hobart) in fully adjusted models. Different patterns of attenuation of associations with inclusion of covariates were evident for different cities. Conclusions For Australian capital cities, greater availability of supermarkets is associated with healthful body size. Marked between-city variations in body size, supermarket availability, and relationships between supermarket availability and body size do not, however, support universal, “one-size-fits-all” solutions to change built environments to support healthful body size.

Lidar backscatter and wind retrievals of the planetary boundary layer height (PBLH) are assimilated into 22-hourly forecasts from the NASA Unified – Weather and Research Forecast (NU-WRF) model during the Plains Elevated Convection at Night (PECAN) campaign on 11 July 2015 in Greensburg, Kansas, using error statistics collected from the model profiles to compute the necessary covariance matrices. Two separate forecast runs using different PBL physics schemes were employed, and comparisons with six independent radiosonde profiles were made for each run. Both of the forecast runs accurately predicted the PBLH and the state variable profiles within the planetary boundary layer during the early morning, and the assimilation had a small impact during this time. In the late afternoon, the forecast runs showed decreased accuracy as the convective boundary layer developed. However, assimilation of the Doppler lidar PBLH observations was found to improve the temperature and V-velocity profiles relative to independent radiosonde profiles. Water vapor was overcorrected, leading to increased differences with independent data. Errors in the U velocity were made slightly larger. The computed forecast error covariances between the PBLH and state variables were found to rise in the late afternoon, leading to the larger improvements in the afternoon. This work represents the first effort to assimilate PBLH into forecast states using ensemble methods.

Abstract Pediatric hypertension is associated with significant target organ damage in children and cardiovascular morbidity in adulthood. Appropriate diagnosis and management per guideline recommendations are inconsistent. In this study, we determined the proportion of missed diagnosis of hypertension and prehypertension and appropriate follow‐up in pediatric patients, stratified by sex, age, race/ethnicity, and weight status. Based on the electronic health record (EHR) data from eight federally qualified health centers, among 62,982 children aged 3 to 18 years, 6233 (10%) had at least one abnormal blood pressure (BP) measurement over twelve months. Among those children whose recorded BPs met the criteria for prehypertension (N = 6178), 14.6% had a diagnosis in the EHR. These children were more likely to be White and have obesity compared with children who met the criteria but were not diagnosed with prehypertension. Among those who met the criteria for hypertension (N = 55), 41.8% had a diagnosis of hypertension in the EHR. Being diagnosed with hypertension was not associated with any examined patient characteristics. Over eleven months, 2837 children had BP ≥ 95th percentile on ≥ 1 visit. Only 13% had guideline‐adherent follow‐up within 1 month and were more likely to be older, female, and of Hispanic ethnicity or “other” race. Over six months, 2902 children had BP ≥ 90th percentile on one visit. 41% had guideline‐adherent follow‐up within 6 months and were more likely to be older, of either White, Hispanic, Asian race, or Hispanic ethnicity. In a community‐based setting, pediatric hypertension and prehypertension were persistently underdiagnosed with low adherence to recommended follow‐up.

The exact function(s) of the lagovirus non-structural protein p23 is unknown as robust cell culture systems for the Rabbit haemorrhagic disease virus (RHDV) and other lagoviruses have not been established. Instead, a range of in vitro and in silico models have been used to study p23, revealing that p23 oligomerizes, accumulates in the cytoplasm, and possesses a conserved C-terminal region with two amphipathic helices. Furthermore, the positional homologs of p23 in other caliciviruses have been shown to possess viroporin activity. Here, we report on the mechanistic details of p23 oligomerization. Site-directed mutagenesis revealed the importance of an N-terminal cysteine for dimerization. Furthermore, we identified cellular interactors of p23 using stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics; heat shock proteins Hsp70 and 110 interact with p23 in transfected cells, suggesting that they ‘chaperone’ p23 proteins before their integration into cellular membranes. We investigated changes to the global transcriptome and proteome that occurred in infected rabbit liver tissue and observed changes to the misfolded protein response, calcium signaling, and the regulation of the endoplasmic reticulum (ER) network. Finally, flow cytometry studies indicate slightly elevated calcium concentrations in the cytoplasm of p23-transfected cells. Taken together, accumulating evidence suggests that p23 is a viroporin that might form calcium-conducting channels in the ER membranes.