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Elijah Anderson's ''code of the streets'' has received considerable attention as a promising approach to understanding youths violence. One area which has received scant attention, however, is the measurement quality of the street code concept. Using data collected from more than 3,300 middle school youths residing in seven geographically and demographically diverse U.S. cities between 2007 and 2009, the authors seek to answer the following questions: (a) What are the psychometric properties of the attitudes toward street code-related violence scale (in terms of dimensionality and internal consistency) across demographic subgroups (i.e., race/ethnicity, sex, and age groups) and social contexts (i.e., cities)? and (b) To what extent does the level of acceptance of the attitudes associated with street code-related violence vary across demographic subgroups and social contexts? Results illustrate that the scale performs similarly across groups and contexts, but the actual level of acceptance of street code-related violence varies considerably. [ABSTRACT FROM AUTHOR]

Youth violence garners considerable attention in the media as well as in public policy debates. In spite of this interest and attention to youth violence, stereotypes fueled by misperceptions about the epidemiology of youth violence often drive these discussions. Urban minority youth, especially males, are typically presented as the 'dark stranger' responsible for much of this violence. Criminal justice and juvenile justice data tend to reinforce this perspective. In this article, the authors call into question the extent to which violent juvenile offending can be characterized as an urban minority male problem. A multisite sample of middle school students was used to examine the distribution of violent offending by sex, race/ethnicity, and community of residence. [ABSTRACT FROM AUTHOR]

Subjects named the colors in which high- and low-frequency words and pronounceable nonwords, otherwise matched, were displayed. Color naming was slower for all three item types than for visually equivalent strings of nonalphanumeric symbols but was no slower for words than for nonwords, nor for high-frequency words than for low-frequency words. Unpronounceable letter strings had intermediate color-naming latencies. However, frequency and lexical status had large effects on latency for reading the same words and pseudowords aloud. Interference is thus predicted not by the strength of association between a letter string and its pronunciation but by the presence of word-like constituents. We argue that the interference from an unprimed noncolor word is due to, and isolates, one of two components of the classic Stroop effect: competition from the whole task set of reading. The other component, response competition, occurs only when lexical access is sufficiently primed. [ABSTRACT FROM AUTHOR]

Objectives: Malnutrition has been shown to increase complications and leads to poor outcomes in surgical patients, but it has not been studied extensively in orthopedic trauma. This study's purpose is to determine the perspective and assessment of nutrition by orthopedic traumatologists., Methods: A survey was created and distributed via REDCap to orthopedic traumatologists at 60 U.S. trauma centers. Out of 183 distributed surveys, 130 surgeons completed the survey (71%). The survey focused on the importance of nutrition and practice patterns in orthopedic trauma., Results: Seventy-five percent of surgeons thought that nutritional status was "very important" to the final outcome of patients with orthopedic trauma injuries, 24% responded "somewhat important" and 1% responded "not important." Furthermore, 88% perform nutritional assessments; most surgeons (77%) utilize nutritional laboratory markers, with the most common markers being albumin, pre-albumin, transferrin and CRP. Additionally, 42% think trending the laboratory markers is important, and 50% are not sure if nutrition markers should be tested at multiple time points. Despite 75% of surgeons believing that nutrition is very important, only 8% discuss it with patients routinely. When asked what is more important for outcomes, nutrition or Vitamin D, almost three times as many surgeons thought nutrition was more important (29% vs 11%, respectively)., Conclusions: While orthopedic traumatologists believe nutrition is an important determinant of patient outcomes, this study shows a clear lack of consensus and variability in practice regarding nutrition among surgeons. Orthopedic trauma surgeons need specific guidelines on how to assess and treat malnutrition in trauma patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Objective: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens., Design: Secondary analysis of phase III, prospective, randomized clinical trial., Setting: Thirty-six US trauma centers., Patient Selection Criteria: Patients who became infected after fixation of tibial plateau or pilon fracture., Outcome Measures and Comparisons: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room., Results: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus., Conclusions: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

It is well known that FGFR2 (fibroblast growth factor receptor 2) signaling is critical for proper lung development. Recent studies demonstrate that epithelial FGFR2 signaling during the saccular phase of lung development (sacculation) regulates alveolar type 1 (AT1) and AT2 cell differentiation. During sacculation, PDGFRA (platelet-derived growth factor receptor-α)-positive lung fibroblasts exist as three functional subtypes: contractile myofibroblasts, extracellular matrix-producing matrix fibroblasts, and lipofibroblasts. All three subtypes are required during alveolarization to establish a niche that supports AT2 epithelial cell self-renewal and AT1 epithelial cell differentiation. FGFR2 signaling directs myofibroblast differentiation in PDGFRA + fibroblasts during alveolar reseptation after pneumonectomy. However, it remains unknown if FGFR2 signaling regulates PDGFRA + myo-, matrix, or lipofibroblast differentiation during sacculation. In this study, FGFR2 signaling was inhibited by temporal expression of a secreted dominant-negative FGFR2b (dnFGFR2) by AT2 cells from embryonic day (E) 16.5 to E18.5. Fibroblast and epithelial differentiation were analyzed at E18.5 and postnatal days 7 and 21. At all time points, the number of myofibroblasts was reduced and the number of lipo-/matrix fibroblasts was increased. AT2 cells are increased and AT1 cells are reduced postnatally, but not at E18.5. Similarly, in organoids made with PDGFRA + fibroblasts from dnFGFR2 lungs, increased AT2 cells and reduced AT1 cells were observed. In vitro treatment of primary wild-type E16.5 adherent saccular lung fibroblasts with recombinant dnFGFR2b/c resulted in reduced myofibroblast contraction. Treatment with the PI3K/AKT activator 740 Y-P rescued the lack of myofibroblast differentiation caused by dnFGFR2b/2c. Moreover, treatment with the PI3K/AKT activator 740 Y-P rescued myofibroblast differentiation in E18.5 fibroblasts isolated from dnFGFR2 lungs.

Background: Clinical guidelines recommend low-molecular-weight heparin for thromboprophylaxis in patients with fractures, but trials of its effectiveness as compared with aspirin are lacking., Methods: In this pragmatic, multicenter, randomized, noninferiority trial, we enrolled patients 18 years of age or older who had a fracture of an extremity (anywhere from hip to midfoot or shoulder to wrist) that had been treated operatively or who had any pelvic or acetabular fracture. Patients were randomly assigned to receive low-molecular-weight heparin (enoxaparin) at a dose of 30 mg twice daily or aspirin at a dose of 81 mg twice daily while they were in the hospital. After hospital discharge, the patients continued to receive thromboprophylaxis according to the clinical protocols of each hospital. The primary outcome was death from any cause at 90 days. Secondary outcomes were nonfatal pulmonary embolism, deep-vein thrombosis, and bleeding complications., Results: A total of 12,211 patients were randomly assigned to receive aspirin (6101 patients) or low-molecular-weight heparin (6110 patients). Patients had a mean (±SD) age of 44.6±17.8 years, 0.7% had a history of venous thromboembolism, and 2.5% had a history of cancer. Patients received a mean of 8.8±10.6 in-hospital thromboprophylaxis doses and were prescribed a median 21-day supply of thromboprophylaxis at discharge. Death occurred in 47 patients (0.78%) in the aspirin group and in 45 patients (0.73%) in the low-molecular-weight-heparin group (difference, 0.05 percentage points; 96.2% confidence interval, -0.27 to 0.38; P<0.001 for a noninferiority margin of 0.75 percentage points). Deep-vein thrombosis occurred in 2.51% of patients in the aspirin group and 1.71% in the low-molecular-weight-heparin group (difference, 0.80 percentage points; 95% CI, 0.28 to 1.31). The incidence of pulmonary embolism (1.49% in each group), bleeding complications, and other serious adverse events were similar in the two groups., Conclusions: In patients with extremity fractures that had been treated operatively or with any pelvic or acetabular fracture, thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin in preventing death and was associated with low incidences of deep-vein thrombosis and pulmonary embolism and low 90-day mortality. (Funded by the Patient-Centered Outcomes Research Institute; PREVENT CLOT ClinicalTrials.gov number, NCT02984384.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and patients with relapsed ALL have a poor prognosis. Detection of ALL blasts remaining at the end of treatment, or minimal residual disease (MRD), and spread of ALL into the central nervous system (CNS) have prognostic importance in ALL. Current methods to detect MRD and CNS disease in ALL rely on the presence of ALL blasts in patient samples. Cell-free DNA, or small fragments of DNA released by cancer cells into patient biofluids, has emerged as a robust and sensitive biomarker to assess cancer burden, although cfDNA analysis has not previously been applied to ALL., Methods: We present a simple and rapid workflow based on NanoporeMinION sequencing of PCR amplified B cell-specific rearrangement of the (IGH) locus in cfDNA from B-ALL patient samples. A cohort of 5 pediatric B-ALL patient samples was chosen for the study based on the MRD and CNS disease status., Results: Quantitation of IGH-variable sequences in cfDNA allowed us to detect clonal heterogeneity and track the response of individual B-ALL clones throughout treatment. cfDNA was detected in patient biofluids with clinical diagnoses of MRD and CNS disease, and leukemic clones could be detected even when diagnostic cell-count thresholds for MRD were not met. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient, even when blasts are not physically present in the biofluid sample., Conclusions: The Nanopore IGH detection workflow to monitor cell-free DNA is a simple, rapid, and inexpensive assay that may ultimately serve as a valuable complement to traditional clinical diagnostic approaches for ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sampathi, Chernyavskaya, Haney, Moore, Snyder, Cox, Fuller, Taylor, Yan, Badgett and Blackburn.)

The mental wellbeing of those living in resource poor and rural localities is a public health priority. Despite evidence of a link between social networks and mental wellbeing, little is known about this relationship in the context of rural and resource poor environments. The current study uses novel social network methodology to investigate the extent to which social network size and composition is related to mental wellbeing in a social housing community in rural England. Data come from 88 individuals living in social housing in Cornwall. These participants are part of a larger study of 329 social housing households surveyed in 2017 and 2018. Mental wellbeing was measured by the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). A series of multivariable linear regression models were used to test associations between social network characteristics and mental wellbeing. Social network size was significantly associated with the SWEMWBS (b = 0.39, p < 0.01), such that individuals with larger networks reported better mental wellbeing, but after controlling for community social cohesion, this effect dissipated. Neither gender composition or talking with network members about health and wellbeing were significantly associated with the SWEMWBS. Findings suggest that both the quantity of social connections and perceptions of community cohesion are moderately associated with mental wellbeing in rural and resource poor localities. As such, efforts to improve mental wellbeing would benefit from targeting multiple aspects of social relationships, rather than focusing solely on increasing the size of individuals' social networks., Competing Interests: Conflicts of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2022.)

Purpose. We investigated how health care systems should communicate with patients about possible exposures to blood-borne pathogens that may have occurred during their care. Our goal was to determine how best to communicate uncertain risk information in a way that would minimize harm to patients, maintain their trust, and encourage patients to seek follow-up treatment. Methods. Participants ( N = 1103) were randomized to receive one of six vignette surveys; 997 (98.4%) responded. All vignettes described the same event, but differed by risk level and recommendations (lower risk v. higher risk) and by communication mode (telephone, letter, social media). We measured participants' perceived risk of blood-borne infection, trust in the health care system, and shared decision making about next clinical steps. Open-ended questions were analyzed using grounded thematic analysis. Results. When the vignette requested patients to undergo testing and practice certain health behaviors (higher risk), participants' likelihood of seeking follow-up testing for blood-borne pathogens and their understanding of health issues increased. Perceived trust was unaffected by risk level or communication processes. Qualitative data indicated a desire for telephone communication from providers known to the patient. Limitations. It is not clear whether higher risk language or objective risk levels in vignettes motivated patients' behavioral intentions. Conclusion. Using higher risk language when disclosing large-scale adverse events increased participants' willingness to seek follow-up care. Implications. Health care organizations' disclosures should focus on the next steps to take after health care exposures. This communication should involve helping patients to understand their personal health issues better, make them feel that they know which steps to take following the receipt of this information, and encouraging them to seek follow-up infectious disease testing in order to better take care of themselves., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The following authors are currently employed by the sponsor (funding agency): AR Elwy, EM Maguire, SM Asch, JM Durfee, BG Bokhour, AL Gifford, TJ Taylor, and TH Wagner., (© The Author(s) 2021.)

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker . This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.

Importance: Organ scarcity means few patients with advanced liver disease undergo a transplant, making equitable distribution all the more crucial. Disparities may arise at any stage in the complex process leading up to this curative therapy., Objective: To examine the rate of and factors associated with referral, wait-listing, and receipt of liver allografts., Design, Setting, and Participants: This retrospective cohort study used linked data from comprehensive electronic medical records and the United Network of Organ Sharing. Adult patients with cirrhosis and a Model for End-Stage Liver Disease with addition of sodium score of at least 15 points between October 1, 2011, and December 31, 2017, were included in the study. Patients were from 129 hospitals in the integrated, US Department of Veterans Affairs health care system and were followed up through December 31, 2018. Statistical analyses were performed from April 28, 2020, to January 31, 2021., Exposures: Sociodemographic (eg, age, insurance, income), clinical (eg, liver disease etiology, severity, comorbidity), and health care facility (eg, complexity, rural or urban, presence of a liver transplant program) factors were evaluated., Main Outcomes and Measures: Referral, wait-listing, and liver transplantation., Results: Of the 34 494 patients with cirrhosis (mean [SD] age, 62 [7.7] years; 33 560 men [97.29%]; 22 509 White patients [65.25%]), 1534 (4.45%) were referred, 1035 (3.00%) were wait-listed, and 549 (1.59%) underwent a liver transplant within 3 years of meeting clinical criteria for transplantation. Patient age of 70 years or older was associated with lower rates of referral (hazard ratio [HR], 0.09; 95% CI, 0.06-0.13), wait-listing (HR, 0.07; 95% CI, 0.04-0.12), and transplant (HR, 0.08; 95% CI, 0.04-0.16). Alcohol etiology for liver cirrhosis was associated with lower rates of referral (HR, 0.38; 95% CI, 0.33-0.44), wait-listing (HR, 0.32; 95% CI, 0.27-0.38), and transplant (HR, 0.30; 95% CI, 0.23-0.37). In addition, comorbidity (none vs >1 comorbidity) was associated with lower rates of referral (HR, 0.47; 95% CI, 0.40-0.56), wait-listing (HR, 0.38; 95% CI, 0.31-0.46), and transplant (HR, 0.28; 95% CI, 0.21-0.38). African American patients were less likely to be referred (HR, 0.82; 95% CI, 0.70-0.95) and wait-listed (HR, 0.73; 95% CI, 0.61-0.88). Patients with lower annual income and those seen in facilities in the West were less likely to be referred (HR, 0.70; 95% CI, 0.53-0.93), wait-listed (HR, 0.48; 95% CI, 0.36-0.64), or undergo a transplant (HR, 0.50; 95% CI, 0.34-0.74). In a review of the medical records for 333 patients who had limited comorbidity but were not referred, organ transplant was considered as a potential option in 176 (52.85%). When documented, medical and psychosocial barriers explained most of the deficits in referral., Conclusions and Relevance: In this cohort study, few patients with advanced liver disease received referrals, were wait-listed, or underwent a transplant. The greatest deficits occurred at the referral step. Although health systems routinely track rates and disparities for organ transplants among wait-listed patients, extending monitoring to the earlier stages may help improve equity and manage potentially modifiable barriers to transplantation.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist., Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections., Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers., Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder., Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence., Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections., Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin., Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

Introduction: Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients., Methods and Analysis: PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections., Ethics and Dissemination: The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients., Trial Registration Number: NCT02984384., Competing Interests: Competing interests: CDM has received grant funding as PI from Merck and receives consulting income from AstraZeneca, Bayer Pharmaceuticals, Janssen/J&J, Merck and Pfizer. ERH is/was the primary investigator of contracts from The Patient-Centred Outcomes Research Institute (PCORI) entitled 'Preventing Venous Thromboembolism: Empowering Patients and Enabling Patient-Centred Care via Health Information Technology' (CE-12-11-4489) and 'Preventing Venous Thromboembolism (VTE): Engaging Patients to Reduce Preventable Harm from Missed/Refused Doses of VTE Prophylaxis' (DI-1603-34596); is the primary investigator of a grant from the Agency for Healthcare Research and Quality (AHRQ) (1R01HS024547) entitled 'Individualised Performance Feedback on Venous Thromboembolism Prevention Practice,' and is a co-investigator on a grant from the NIH/NHLBI (R21HL129028) entitled 'Analysis of the Impact of Missed Doses of Venous Thromboembolism Prophylaxis'; receives research grant support from the DOD/Army Medical Research Acquisition Activity and has received grant support from the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); receives book royalties from Lippincott, Williams, Wilkins; and is a paid consultant to Vizient for their HIIN Venous Thromboembolism (VTE) Prevention Action Network., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Personas, based on customer or population data, are widely used to inform design decisions in the commercial sector. The variety of methods available means that personas can be produced from projects of different types and scale., Objective: This study aims to experiment with the use of personas that bring together data from a survey, household air measurements and electricity usage sensors, and an interview within a research and innovation project, with the aim of supporting eHealth and eWell-being product, process, and service development through broadening the engagement with and understanding of the data about the local community., Methods: The project participants were social housing residents (adults only) living in central Cornwall, a rural unitary authority in the United Kingdom. A total of 329 households were recruited between September 2017 and November 2018, with 235 (71.4%) providing complete baseline survey data on demographics, socioeconomic position, household composition, home environment, technology ownership, pet ownership, smoking, social cohesion, volunteering, caring, mental well-being, physical and mental health-related quality of life, and activity. K-prototype cluster analysis was used to identify 8 clusters among the baseline survey responses. The sensor and interview data were subsequently analyzed by cluster and the insights from all 3 data sources were brought together to produce the personas, known as the Smartline Archetypes., Results: The Smartline Archetypes proved to be an engaging way of presenting data, accessible to a broader group of stakeholders than those who accessed the raw anonymized data, thereby providing a vehicle for greater research engagement, innovation, and impact., Conclusions: Through the adoption of a tool widely used in practice, research projects could generate greater policy and practical impact, while also becoming more transparent and open to the public., (©Andrew James Williams, Tamaryn Menneer, Mansi Sidana, Tim Walker, Kath Maguire, Markus Mueller, Cheryl Paterson, Michael Leyshon, Catherine Leyshon, Emma Seymour, Zoë Howard, Emma Bland, Karyn Morrissey, Timothy J Taylor. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 16.02.2021.)

Importance: Machine-learning algorithms offer better predictive accuracy than traditional prognostic models but are too complex and opaque for clinical use., Objective: To compare different machine learning methods in predicting overall mortality in cirrhosis and to use machine learning to select easily scored clinical variables for a novel cirrhosis prognostic model., Design, Setting, and Participants: This prognostic study used a retrospective cohort of adult patients with cirrhosis or its complications seen in 130 hospitals and affiliated ambulatory clinics in the integrated, national Veterans Affairs health care system from October 1, 2011, to September 30, 2015. Patients were followed up through December 31, 2018. Data were analyzed from October 1, 2017, to May 31, 2020., Exposures: Potential predictors included demographic characteristics; liver disease etiology, severity, and complications; use of health care resources; comorbid conditions; and comprehensive laboratory and medication data. Patients were randomly selected for model development (66.7%) and validation (33.3%). Three different statistical and machine learning methods were evaluated: gradient descent boosting, logistic regression with least absolute shrinkage and selection operator (LASSO) regularization, and logistic regression with LASSO constrained to select no more than 10 predictors (partial pathway model). Predictor inclusion and model performance were evaluated in a 5-fold cross-validation. Last, the predictors identified in the most parsimonious (the partial path) model were refit using maximum-likelihood estimation (Cirrhosis Mortality Model [CiMM]), and its predictive performance was compared with that of the widely used Model for End Stage Liver Disease with sodium (MELD-Na) score., Main Outcomes and Measures: All-cause mortality., Results: Of the 107 939 patients with cirrhosis (mean [SD] age, 62.7 [9.6] years; 96.6% male; 66.3% white, 18.4% African American), the annual mortality rate ranged from 8.8% to 15.3%. In total, 32.7% of patients died within 3 years, and 46.2% died within 5 years after the index date. Models predicting 1-year mortality had good discrimination for the gradient descent boosting (area under the receiver operating characteristics curve [AUC], 0.81; 95% CI, 0.80-0.82), logistic regression with LASSO regularization (AUC, 0.78; 95% CI, 0.77-0.79), and the partial path logistic model (AUC, 0.78; 95% CI, 0.76-0.78). All models showed good calibration. The final CiMM model with machine learning-derived clinical variables offered significantly better discrimination than the MELD-Na score, with AUCs of 0.78 (95% CI, 0.77-0.79) vs 0.67 (95% CI, 0.66-0.68) for 1-year mortality, respectively (DeLong z = 17.00; P < .001)., Conclusions and Relevance: In this study, simple machine learning techniques performed as well as the more advanced ensemble gradient boosting. Using the clinical variables identified from simple machine learning in a cirrhosis mortality model produced a new score more transparent than machine learning and more predictive than the MELD-Na score.

Background: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers., Objective: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions., Methods: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies., Results: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting., Discussion: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can inform evidence-based decision making and practice. https://doi.org/10.1289/EHP6745.

Objective: Mean uterine artery pulsatility index (meanUAPI) is commonly measured at 11-13+6 weeks to predict adverse pregnancy outcomes including hypertensive disorders and small-for-gestational age. The aims of this study were to establish a population-specific reference range for meanUAPI at <11 weeks, to determine if an abnormal meanUAPI at <11 weeks was associated with adverse pregnancy outcome, and to assess changes in meanUAPI between <11 weeks and 11-13+6 weeks., Methods: A prospective cohort was examined at <11 weeks and at 11-13+6 weeks to develop reference ranges for meanUAPI. Based on these regression models, meanUAPI Z-scores were compared between outcome groups using a two-sample t test. Longitudinal changes in the meanUAPI between <11 and 11-13+6 weeks were assessed by two-way mixed ANOVA., Results: Prior to 11 weeks, there was no significant difference in meanUAPI between normal (n = 622) and adverse (n = 80) outcomes (mean [95% CI]: 2.62 [2.57-2.67] and 2.67 [2.50-2.84], respectively; p = 0.807). At 11-13+6 weeks, meanUAPI was significantly higher in the adverse (n = 66) compared with the normal (n = 535) outcome group (mean [95% CI]: 1.87 [1.70-2.03] and 1.67 [1.63-1.72], respectively; p = 0.040). There was a statistically significant decrease (p < 0.0001) in meanUAPI between the two time points., Conclusion: MeanUAPI measured at <11 weeks' gestation does not appear to be a useful marker for the prediction of placental-related adverse pregnancy outcomes, supporting an argument for the prediction of risk at 11-13+6 weeks' gestation., (© 2019 S. Karger AG, Basel.)

Background: First-trimester miscarriage is common, with women increasingly offered an ultrasound scan early in the first trimester to assess the status of their pregnancy. Ultrasound is uniquely situated to significantly impact the clinical management of these women., Aims: This study aims to determine whether there were any differences in the early ultrasound appearances of pregnancies that continued to be viable or resulted in miscarriage before 12 weeks gestation., Materials and Methods: This was a prospective cohort study including ultrasound measurements: mean sac diameter (MSD), yolk sac diameter (YSD), crown-rump length (CRL), fetal heart rate (FHR), trophoblast thickness, trophoblast volume (TTV) and mean uterine artery pulsatility index (meanUAPI). Regression models were fitted for each parameter and Z-scores compared between cohorts that progressed or miscarried after the scan but before 12 weeks gestation. Logistic regression analysis was used to create a prediction model for miscarriage prior to 12 weeks gestation based on the standardised ultrasound measurements recorded during the early first-trimester scan., Results: Comparison of Z-Scores for meanUAPI, TTV, FHR and MSD demonstrated significant variation between the two groups. The proposed logistic regression model resulted in an area under the receiver operator curve of 0.81. At a false-positive rate of 30%, the model resulted in a sensitivity of 76% (95% CI 64-89%)., Conclusion: The combination of FHR, meanUAPI, TTV in a prediction model for miscarriage may prove to be of value for ongoing pregnancy management in the first trimester., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Neural stem and progenitor cells (NSPCs) are an extremely important group of cells that form the central nervous system during development and have the potential to repair damage in conditions such as stroke impairment, spinal cord injury and Parkinson's disease degradation. Current schemes for separation of NSPCs are inadequate due to the complexity and diversity of cells in the population and lack sufficient markers to distinguish diverse cell types. This study presents an unbiased high-resolution separation and characterization of NSPC subpopulations using direct current insulator-based dielectrophoresis (DC-iDEP). The properties of the cells were identified by the ratio of electrokinetic (EK) to dielectrophoretic (DEP) mobilities. The ratio factor of NSPCs showed more heterogeneity variance (SD = 3.4-3.9) than the controlled more homogeneous human embryonic kidney cells (SD = 1.1), supporting the presence of distinct subpopulations of cells in NSPC cultures. This measure reflected NSPC fate potential since the ratio factor distribution of more neurogenic populations of NSPCs was distinct from the distribution of astrogenic NSPC populations (confidence level >99.9%). The abundance of NSPCs captured with different ranges of ratio of EK to DEP mobilities also exhibit final fate trends consistent with established final fates of the chosen samples. DC-iDEP is a novel, label-free and non-destructive method for differentiating and characterizing, and potentially separating, neural stem cell subpopulations that differ in fate.

Aim:  The complications that arise when performing meta-analysis of datasets from multiple metabolomics studies are addressed with computational methods that ensure data quality, completeness of metadata and accurate interpretation across studies. Results & methodology: This paper presents an integrated system of quality control (QC) methods to assess metabolomics results by evaluating the data acquisition strategies and metabolite identification process when integrating datasets for meta-analysis. An ontology knowledge base and a rule-based system representing the experiment and chemical background information direct the processes involved in data integration and QC verification. A diabetes meta-analysis study using these QC methods finds putative biomarkers that differ between cohorts. Conclusion: The methods presented here ensure the validity of meta-analysis when integrating data from different metabolic profiling studies.

The optimal strategy in detection theory is to partition the decision axis at a criterion C, labeling all events that score above C "Signal", and all those that fall below "Noise." The optimal position of C, C*, depends on signal probability and payoffs. If observers place their criterion at some place other than C*, they suffer a loss in the Expected Value (EV) of payoffs over the course of many decisions. We provide an explicit equation for the degree of loss, where it is shown that the falloff in value will be steep in contexts of good discrimination and will be a flatter gradient in contexts of poor discrimination. It is these gradients of loss in EV that, in theory, drive C toward C*, strongly when discrimination is good, weakly when discrimination is poor. When signal probabilities or distributions variances are unequal, the basins of attraction are asymmetric, so that dynamic adjustments in C will be asymmetric, and thus, as we show, will leave it biased. We address our analysis to acquisition speed, response variability, discrimination reversal and other aspects of discriminated performance. In the final section, we develop an error correction model that predicts empirically observed deviations from C* that are inconsistent with the standard model, but follow from the proposed model given knowledge of d'. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

There are gender-specific variations in the epidemiology and clinical course of hepatitis C virus (HCV) infection. However, few long-term longitudinal studies have examined trends in the incidence and prevalence of serious liver complications among women compared with men with HCV infection. We used the Veterans Administration Corporate Data Warehouse to identify all veterans with positive HCV viraemia from January 2000 to December 2013. We calculated gender-specific annual incidence and prevalence rates of cirrhosis, decompensated cirrhosis and hepatocellular cancer (HCC) adjusting for age, diabetes, HIV and alcohol use. We also calculated the average annual per cent change (AAPC) for each outcome by gender using piecewise linear regression in the Joinpoint software. We identified 264 409 HCV-infected veterans during 2000-2013, of whom 7162 (2.7%) were women. There were statistically significant increases over time in the incidence rates of cirrhosis, decompensated cirrhosis and HCC for both men and women. The annual-adjusted incidence rates of cirrhosis, decompensated cirrhosis and HCC were higher in men than women for all study years. However, these complications increased at a similar rate in both groups. Specifically, the AAPC for cirrhosis was 13.1 and 15.2, while it was 15.6 and 16.9 for decompensated cirrhosis and 21.0 and 25.3 for HCC in men and women, respectively (all test of parallelism not significant). The results were similar in the prevalence analyses, although AAPCs were slightly smaller for each outcome. In conclusion, we found an ongoing upward trend in the incidence and prevalence of HCV complications in this cohort of HCV-infected women. This increase in cirrhosis complications in women with active HCV infection is similar to those in men. With cure from HCV now becoming a reality, most of the projected burden of HCV is potentially preventable. However, benefits of HCV treatment will need to extend to all patients in order to stem the rising tide of HCV complications., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1.3 mg/m 2 twice-weekly, on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11 of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood samples were obtained and the plasma was harvested on day 8 over 0-72 hours postdose to measure bortezomib concentrations by liquid chromatography-tandem mass spectrometry. Concentration-time data were analyzed by nonlinear mixed-effects modeling. Covariates were examined using forward addition (P < .01)/backward elimination (P < .001). Data were included from 104 patients (49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2-11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3-compartment model with linear elimination. Body surface area adequately accounted for variability in clearance (exponent 0.97), supporting body surface area-based dosing. Stratified visual predictive check simulations verified that neither age group nor patient population represented sources of meaningful pharmacokinetic heterogeneity not accounted for by the final population pharmacokinetic model. Following administration of 1.3 mg/m 2 intravenous bortezomib doses, body surface area-normalized clearance in pediatric patients was similar to that observed in adult patients, thereby indicating that this dose achieves similar systemic exposures in pediatric patients., (© 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Background: Homeless veterans often have multiple health care and psychosocial needs, including assistance with access to housing and health care, as well as support for ongoing treatment engagement. The Department of Veterans Affairs (VA) developed specialized Homeless Patient Alignment Care Teams (HPACT) with the goal of offering an integrated, "one-stop program" to address housing and health care needs of homeless veterans. However, while 70% of HPACT's veteran enrollees have co-occurring mental health and substance use disorders, HPACT does not have a uniform, embedded treatment protocol for this subpopulation. One wraparound intervention designed to address the needs of homeless veterans with co-occurring mental health and substance use disorders which is suitable to be integrated into HPACT clinic sites is the evidence-based practice called Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking-Veterans Edition, or MISSION-Vet. Despite the promise of MISSION-Vet within HPACT clinics, implementation of an evidence-based intervention within a busy program like HPACT can be difficult. The current study is being undertaken to identify an appropriate implementation strategy for MISSION-Vet within HPACT. The study will test the implementation platform called Facilitation and compared to implementation as usual (IU). The aims of this study are as follows: (1) Compare the extent to which IU or Facilitation strategies achieve fidelity to the MISSION-Vet intervention as delivered by HPACT homeless provider staff. (2) Compare the effects of Facilitation and IU strategies on the National HPACT Performance Measures. (3) Compare the effects of IU and Facilitation on the permanent housing status. (4) Identify and describe key stakeholders' (patients, providers, staff) experiences with, and perspectives on, the barriers to, and facilitators of implementing MISSION., Design: Type III Hybrid modified stepped wedge implementation comparing IU to Facilitation across seven HPACT teams in three sites in the greater Los Angeles VA system. This is a cluster randomized trial., Discussion: Integrating MISSION-Vet within HPACT has the potential to improve the health of thousands of veterans, but it is crucial to implement the intervention appropriately in order for it to succeed. The lessons learned in this protocol could assist with a larger roll-out of MISSION within HPACT. This protocol is registered with clinicaltrials.gov and was assigned the number NCT 02942979.

Patients surgically treated for infection after extremity fractures are typically discharged with a 6- to 12-week antibiotic regimen. Intravenous (IV) antibiotics are associated with significant cost and potential complications of deep vein thrombosis, line clotting, and sepsis. Many of the pathogens that cause musculoskeletal infection have both oral (PO) and IV antibiotic options with adequate bioavailability and antibacterial effect, yet IV antibiotics remain the standard of care absent evidence that PO options are clinically as efficacious. The POvIV study is a prospective, multicenter, randomized trial to compare PO with IV antibiotic therapy in patients with postoperative wound infections after extremity fractures. Patients between the ages of 18 and 84 who have a culture-positive surgical site infection after internal fixation for fracture repair or arthrodesis are approached for this study, and if they provide consent, are randomly assigned to receive either PO or IV antibiotics. Antibiotic selection is based on culture and sensitivity results. Randomization determines the route of administration. Patients are followed for 1 year after study enrollment. This study will be the largest prospective randomized trial to evaluate the safety and effectiveness of PO antibiotic use for treatment of postoperative wound infections. Results will inform clinician decisions on antibiotic delivery in patients with postoperative wound infections.

West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Youth partnerships are a promising but understudied strategy for prevention and health promotion. Specifically, little is known about how the functioning of youth partnerships differs from that of adult partnerships. Accordingly, this study compared the functioning of youth partnerships with that of adult partnerships. Several aspects of partnership functioning, including leadership, task focus, cohesion, participation costs and benefits, and community support, were examined. Standardized partnership functioning surveys were administered to participants in three smoke-free youth coalitions (n = 44; 45 % female; 43 % non-Hispanic white; mean age = 13) and in 53 Communities That Care adult coalitions (n = 673; 69 % female; 88 % non-Hispanic white; mean age = 49). Multilevel regression analyses showed that most aspects of partnership functioning did not differ significantly between youth and adult partnerships. These findings are encouraging given the success of the adult partnerships in reducing community-level rates of substance use and delinquency. Although youth partnership functioning appears to be strong enough to support effective prevention strategies, youth partnerships faced substantially more participation difficulties than adult partnerships. Strategies that youth partnerships can use to manage these challenges, such as creative scheduling and increasing opportunities for youth to help others directly, are discussed.

Aims: Myocardial deformation is a key to clinical decision-making. Feature-tracking cardiovascular magnetic resonance (FT-CMR) provides quantification of motion and strain using standard steady-state in free-precession (SSFP) imaging, which is part of a routine CMR left ventricular (LV) study protocol. An accepted definition of a normal range is essential if this technique is to enter the clinical arena., Methods and Results: One hundred healthy individuals, with 10 men and women in each of 5 age deciles from 20 to 70 years, without a history of cardiovascular disease, diabetes, renal impairment, or family history of cardiovascular disease, and with a normal stress echocardiogram, underwent FT-CMR assessment of LV myocardial strain and strain rate using SSFP cines.Peak systolic longitudinal strain (Ell) was -21.3 ± 4.8%, peak systolic circumferential strain (Ecc) was -26.1 ± 3.8%, and peak systolic radial strain (Err) was 39.8 ± 8.3%. On Bland-Altman analyses, peak systolic Ecc had the best inter-observer agreement (bias 0.63 ± 1.29% and 95% CI -1.90 to 3.16) and peak systolic Err the least inter-observer agreement (bias 0.13 ± 6.41 and 95% CI -12.44 to 12.71). There was an increase in the magnitude of peak systolic Ecc with advancing age, which was greatest in subjects over the age of 50 years (R(2) = 0.11, P = 0.003). There were significant gender differences (P < 0.001) in peak systolic Ell, with a greater magnitude of deformation in females (-22.7%) than in males (-19.3%)., Conclusion: Normal values for myocardial strain measurements using FT-CMR are provided. All circumferential and longitudinal based variables had excellent intra- and inter-observer variability., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Purpose: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines., Methods: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast cancer. Mesna (360 mg/m2) or saline administration occurred 15 minutes prior and three hours post doxorubicin. Pre-treatment and post-treatment measurements of oxidative stress, TNF-α and related cytokines were evaluated during the two experimental cycles of chemotherapy., Results: Co-administration of mesna with chemotherapy reduced post-treatment levels of TNF-related cytokines and TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2) (p = 0.05 and p = 0.002, respectively). Patients with the highest pre-treatment levels of each cytokine and its receptors were the most likely to benefit from mesna co-administration., Conclusions: The extracellular anti-oxidant mesna, when co-administered during a single cycle of doxorubicin, reduced levels of TNF-α and its receptors after that cycle of therapy, demonstrating for the first time a clinical interaction between mesna and doxorubicin, drugs often coincidentally co-administered in multi-agent regimens. These findings support further investigation to determine whether rationally-timed mesna co-administration with redox active chemotherapy may prevent or reduce the cascade of events that lead to CICI., Trial Registration: clinicaltrials.gov NCT01205503.

Purpose: To compare cardiovascular magnetic resonance-feature tracking (CMR-FT) with spatial modulation of magnetization (SPAMM) tagged imaging for the calculation of short and long axis Lagrangian strain measures in systole and diastole., Materials and Methods: Healthy controls (n = 35) and patients with dilated cardiomyopathy (n = 10) were identified prospectively and underwent steady-state free precession (SSFP) cine imaging and SPAMM imaging using a gradient-echo sequence. A timed offline analysis of images acquired at identical horizontal long and short axis slice positions was performed using CMR-FT and dynamic tissue-tagging (CIMTag2D). Agreement between strain and strain rate (SR) values calculated using these two different methods was assessed using the Bland-Altman technique., Results: Across all participants, there was good agreement between CMR-FT and CIMTag for calculation of peak systolic global circumferential strain (-22.7 ± 6.2% vs. -22.5 ± 6.9%, bias 0.2 ± 4.0%) and SR (-1.35 ± 0.42 1/s vs. -1.22 ± 0.42 1/s, bias 0.13 ± 0.33 1/s) and early diastolic global circumferential SR (1.21 ± 0.44 1/s vs. 1.07 ± 0.30 1/s, bias -0.14 ± 0.34 1/s) at the subendocardium. There was satisfactory agreement for derivation of peak systolic global longitudinal strain (-18.1 ± 5.0% vs. -16.7 ± 4.8%, bias 1.3 ± 3.8%) and SR (-1.04 ± 0.29 1/s vs. -0.95 ± 0.32 1/s, bias 0.09 ± 0.26 1/s). The weakest agreement was for early diastolic global longitudinal SR (1.10 ± 0.40 1/s vs. 0.67 ± 0.32 1/s, bias -0.42 ± 0.40 1/s), although the correlation remained significant (r = 0.42, P < 0.01). CMR-FT generated these data over four times quicker than CIMTag., Conclusion: There is sufficient agreement between systolic and diastolic strain measures calculated using CMR-FT and myocardial tagging for CMR-FT to be considered as a potentially feasible and rapid alternative., (© 2014 Wiley Periodicals, Inc.)

Objectives: Climate change has the potential to threaten human health and the environment. Managers in healthcare systems face significant challenges to balance carbon mitigation targets with operational decisions about patient care. Critical care units are major users of energy and hence more evidence is needed on their carbon footprint., Study Design: The authors explore a methodology which estimates electricity use and associated carbon emissions within a Critical Care Unit (CCU)., Methods: A bottom-up model was developed and calibrated which predicted the electricity consumed and carbon emissions within a CCU based on the type of patients treated and working practices in a case study in Cornwall, UK., Results: The model developed was able to predict the electricity consumed within CCU with an error of 1% when measured against actual meter readings. Just under half the electricity within CCU was used for delivering care to patients and monitoring their condition., Conclusions: A model was developed which accurately predicted the electricity consumed within a CCU based on patient types, medical devices used and working practice. The model could be adapted to enable it to be used within hospitals as part of their planning to meet carbon reduction targets., (Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Over the years numerous models of S I S (susceptible --> infected --> susceptible) disease dynamics unfolding on networks have been proposed. Here, we discuss the links between many of these models and how they can be viewed as more general motif-based models. We illustrate how the different models can be derived from one another and, where this is not possible, discuss extensions to established models that enables this derivation. We also derive a general result for the exact differential equations for the expected number of an arbitrary motif directly from the Kolmogorov/master equations and conclude with a comparison of the performance of the different closed systems of equations on networks of varying structure.

The observation of apparent power laws in neuronal systems has led to the suggestion that the brain is at, or close to, a critical state and may be a self-organised critical system. Within the framework of self-organised criticality a separation of timescales is thought to be crucial for the observation of power-law dynamics and computational models are often constructed with this property. However, this is not necessarily a characteristic of physiological neural networks-external input does not only occur when the network is at rest/a steady state. In this paper we study a simple neuronal network model driven by a continuous external input (i.e. the model does not have an explicit separation of timescales from seeding the system only when in the quiescent state) and analytically tuned to operate in the region of a critical state (it reaches the critical regime exactly in the absence of input-the case studied in the companion paper to this article). The system displays avalanche dynamics in the form of cascades of neuronal firing separated by periods of silence. We observe partial scale-free behaviour in the distribution of avalanche size for low levels of external input. We analytically derive the distributions of waiting times and investigate their temporal behaviour in relation to different levels of external input, showing that the system's dynamics can exhibit partial long-range temporal correlations. We further show that as the system approaches the critical state by two alternative 'routes', different markers of criticality (partial scale-free behaviour and long-range temporal correlations) are displayed. This suggests that signatures of criticality exhibited by a particular system in close proximity to a critical state are dependent on the region in parameter space at which the system (currently) resides.

We present the assessment of predictions for Template-Free Modeling in CASP10 and a report on the first ROLL experiment wherein predictions are collected year round for review at the regular CASP season. Models were first clustered so that duplicated or very similar ones were grouped together and represented by one model in the cluster. The representatives were then compared with targets using GDT&#95;TS, QCS, and three additional superposition-independent score functions newly developed for CASP10. For each target, the top 15 representatives by each score were pooled to form the Top15Union set. All models in this set were visually inspected by four of us independently using the new plugin, EvalScore, which we developed with the UCSF Chimera group. The best models were selected for each target after extensive debate among the four examiners. Groups were ranked by the number of targets (hits) for which a group's model was selected as one of the best models. The Keasar group had most hits in both categories, with four of 19 FM and eight of 36 ROLL targets. The most successful prediction servers were QUARK from Zhang's group for FM category with three hits and Zhang-server for the ROLL category with seven hits. As observed in CASP9, many successful groups were not true "template-free" modelers but used remote templates and/or server models to obtain their winning models. The results of the first ROLL experiment were broadly similar to those of the CASP10 FM exercise., (Copyright © 2013 Wiley Periodicals, Inc.)

In CASP10, for the first time, contact-assisted structure predictions have been assessed. Sets of pairs of contacting residues from target structures were provided to predictors for a second round of prediction after the initial round in which they were given only sequences. The objective of the experiment was to measure model quality improvement resulting from the added contact information and thereby assess and help develop so-called hybrid prediction methods--methods where some experimentally determined distance constraints are used to augment de novo computational prediction methods. The results of the experiment were, overall, quite promising., (Copyright © 2013 Wiley Periodicals, Inc.)

For the 10th experiment on Critical Assessment of the techniques of protein Structure Prediction (CASP), the prediction target proteins were broken into independent evaluation units (EUs), which were then classified into template-based modeling (TBM) or free modeling (FM) categories. We describe here how the EUs were defined and classified, what issues arose in the process, and how we resolved them. EUs are frequently not the whole target proteins but the constituting structural domains. However, the assessors from CASP7 on combined more than one domain into 1 EU for some targets, which implied that the assessment also included evaluation of the prediction of the relative position and orientation of these domains. In CASP10, we followed and expanded this notion by defining multidomain EUs for a number of targets. These included 3 EUs, each made of two domains of familiar fold but arranged in a novel manner and for which the focus of evaluation was the interdomain arrangement. An EU was classified to the TBM category if a template could be found by sequence similarity searches and to FM if a structural template could not be found by structural similarity searches. The EUs that did not fall cleanly in either of these cases were classified case-by-case, often including consideration of the overall quality and characteristics of the predictions., (Copyright © 2013 Wiley Periodicals, Inc.)

How might religion shape intergroup conflict? We tested whether religious infusion-the extent to which religious rituals and discourse permeate the everyday activities of groups and their members-moderated the effects of two factors known to increase intergroup conflict: competition for limited resources and incompatibility of values held by potentially conflicting groups. We used data from the Global Group Relations Project to investigate 194 groups (e.g., ethnic, religious, national) at 97 sites around the world. When religion was infused in group life, groups were especially prejudiced against those groups that held incompatible values, and they were likely to discriminate against such groups. Moreover, whereas disadvantaged groups with low levels of religious infusion typically avoided directing aggression against their resource-rich and powerful counterparts, disadvantaged groups with high levels of religious infusion directed significant aggression against them-despite the significant tangible costs to the disadvantaged groups potentially posed by enacting such aggression. This research suggests mechanisms through which religion may increase intergroup conflict and introduces an innovative method for performing nuanced, cross-societal research.

In this paper, we study a simple model of a purely excitatory neural network that, by construction, operates at a critical point. This model allows us to consider various markers of criticality and illustrate how they should perform in a finite-size system. By calculating the exact distribution of avalanche sizes, we are able to show that, over a limited range of avalanche sizes which we precisely identify, the distribution has scale free properties but is not a power law. This suggests that it would be inappropriate to dismiss a system as not being critical purely based on an inability to rigorously fit a power law distribution as has been recently advocated. In assessing whether a system, especially a finite-size one, is critical it is thus important to consider other possible markers. We illustrate one of these by showing the divergence of susceptibility as the critical point of the system is approached. Finally, we provide evidence that power laws may underlie other observables of the system that may be more amenable to robust experimental assessment.

Increasing greenhouse gas emissions threaten human health and the environment. In response, healthcare managers face significant challenges in balancing operational decisions about patient care with carbon mitigation targets. We explore a bottom-up modeling framework to aid in the decision-making for both carbon and cost in healthcare, using data from a case study in Cornwall, UK. A model was built and run for secondary healthcare, specifically outpatient clinics, theater lists, beds, and diagnostic facilities. Five scenarios were tested: business-as-usual; service expansion; site closure; water temperature reduction; and theater optimization. The estimated emissions from secondary healthcare in Cornwall ran to 5787 T CO(2)eq with patient travel adding 2215 T CO(2)eq. Closing selected sites would have reduced this by 4% (261 T CO(2)eq), a reduction less than the resulting increases in patient transport emissions. Reducing hot water temperatures by 5 °C and improving theater usage would lower the footprint by 0.7% (44 T CO(2)eq) and 0.08% (5 T CO(2)eq), respectively. We consider bottom-up models important tools in the process of estimating and modeling the carbon footprint of healthcare. For the carbon reduction targets of the healthcare sector to be met, the use of these bottom-up models in decision making and forward planning is pivotal.

A substantial portion of the atmospheric particle budget is of biological origin (human and animal dander, plant and insect debris, etc.). These bioaerosols can be considered information-rich packets of biochemical data specific to the organism of origin. In this study, bioaerosol samples from various indoor environments were analyzed to create identifiable patterns attributable to a source level of occupation. Air samples were collected from environments representative of human high-traffic- and low-traffic indoor spaces along with direct human skin sampling. In all settings, total suspended particulate matter was collected and the total aerosol protein concentration ranged from 0.03 to 1.2 μg/m(3). High performance liquid chromatography was chosen as a standard analysis technique for the examination of aqueous aerosol extracts to distinguish signatures of occupation compared to environmental background. The results of this study suggest that bioaerosol "fingerprinting" is possible with the two test environments being distinguishable at a 97% confidence interval.

Aim: To investigate interleukin-6 (IL-6), mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P in the gastrointestinal mucosa of children with abdominal pain., Methods: Formalin-fixed paraffin-embedded gastrointestinal biopsy blocks from patients (n = 48) with non-inflammatory bowel disease (irritable bowel syndrome and functional abdominal pain) and inflammatory bowel disease were sectioned and stained for IL-6, mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P. All children had chronic abdominal pain as part of their presenting symptoms. Biopsy phenotype was confirmed by a pathologist, blinded to patient information. Descriptive statistics, chi-square, and independent sample t tests were used to compare differences between the inflammatory and non-inflammatory groups., Results: The cohort (n = 48), mean age 11.9 years (SD = 2.9), 54.2% females, 90% Caucasian, was comprised of a non-inflammatory (n = 26) and an inflammatory (n = 22) phenotype. There was a significant negative correlation between substance P expression and mast cell count (P = 0.05, r = -0.373). Substance P was found to be expressed more often in female patient biopsies and more intensely in the upper gastrointestinal mucosa as compared to the lower mucosa. There were significantly increased gastrointestinal mucosal immunoreactivity to IL-6 (P = 0.004) in the inflammatory phenotype compared to non-inflammatory. Additionally, we found significantly increased mast cells (P = 0.049) in the mucosa of the non-inflammatory phenotype compared to the inflammatory group. This difference was particularly noted in the lower colon biopsies., Conclusion: The findings of this study yield preliminary evidence in identifying biomarkers of undiagnosed abdominal pain in children and may suggest candidate genes for future evaluation.

The purpose of this review is to investigate the feasibility of bioaerosol fingerprinting based on current understanding of cellular debris (with emphasis on human-emitted particulates) in aerosols and arguments regarding sampling, sensitivity, separations, and detection schemes. Target aerosol particles include cellular material and proteins emitted by humans, animals, and plants and can be regarded as information-rich packets that carry biochemical information specific to the living organisms present where the sample is collected. In this work we discuss sampling and analysis techniques that can be integrated with molecular (e.g. protein)-detection procedures to properly assess the aerosolized cellular material of interest. Developing a detailed understanding of bioaerosol molecular profiles in different environments suggests exciting possibilities of bioaerosol analysis with applications ranging from military defense to medical diagnosis and wildlife identification.

Surface mining is a common method for extracting coal in the coal fields of eastern Kentucky. Using the Forestry Reclamation Approach (FRA), which emphasizes the use of minimally compacted or loose-dumped spoil as a growth medium for trees, reclamation practitioners are successfully reestablishing forests. Yet, questions remain regarding the effects FRA has on the quality of waters discharged to receiving streams. To examine the effect of FRA on water quality, this study compared waters that were discharged from three types of spoils: predominantly brown, weathered sandstone (BROWN); predominantly gray, unweathered sandstone (GRAY); and an equal mixture of both aforementioned sandstones and shale (MIXED). The water quality parameters pH, EC, Ca, K, Mg, Na, NO-N, NH-N, SO, Cl, TC, suspended sediment concentration (SSC), settleable solids (SS), and turbidity were monitored over a 2-yr period on six 0.4-ha plots (two replications per spoil type). Generally, levels of Cl, SO, Ca, NO-N, NH-N, SS, SSC, and turbidity decreased over time. The pH for all spoils increased from about 7.5 to 8.5. The EC remained relatively level in the BROWN spoil, whereas the GRAY and MIXED spoils had downward trajectories that were approaching 500 μS cm. The value of 500 μS cm has been reported as the apparent threshold at which certain taxa such as Ephemeroptera (e.g., Mayfly) recolonize disturbed headwater streams of eastern Kentucky and adjacent coal-producing Appalachian states., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

In this paper we present a model describing susceptible-infected-susceptible-type epidemics spreading on a dynamic contact network with random link activation and deletion where link activation can be locally constrained. We use and adapt an improved effective degree compartmental modeling framework recently proposed by Lindquist et al. [J. Math Biol. 62, 143 (2010)] and Marceau et al. [Phys. Rev. E 82, 036116 (2010)]. The resulting set of ordinary differential equations (ODEs) is solved numerically, and results are compared to those obtained using individual-based stochastic network simulation. We show that the ODEs display excellent agreement with simulation for the evolution of both the disease and the network and are able to accurately capture the epidemic threshold for a wide range of parameters. We also present an analytical R0 calculation for the dynamic network model and show that, depending on the relative time scales of the network evolution and disease transmission, two limiting cases are recovered: (i) the static network case when network evolution is slow and (ii) homogeneous random mixing when the network evolution is rapid. We also use our threshold calculation to highlight the dangers of relying on local stability analysis when predicting epidemic outbreaks on evolving networks.

Background: Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10-15% of people worldwide and has economic consequences in the United States of over $30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2:1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes., Methods: Irritable bowel syndrome patients (n=12) that met Rome III Criteria for IBS longer than 6months were compared with healthy matched controls (n=12). Peripheral whole blood from fasting participants was collected and RNA was extracted. The expression of 96 inflammatory genes was then analyzed using a custom quantitative real-time PCR array., Key Results: CCL-16 gene expression was upregulated by 7.46-fold in IBS patients when compared with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation patients when compared with both controls and IBS-diarrhea patients., Conclusions & Inferences: These results further suggest a subclinical inflammatory component underlying IBS. To better understand the phenotypic differences in IBS it is important to broaden the study of these inflammatory and other biomarkers., (Published 2011. This article is a US Government work and is in the public domain in the USA.)

Insulator-based dielectrophoresis (iDEP) is a powerful tool for separating and characterizing particles, yet it is limited by a lack of quantitative characterizations. Here, this limitation is addressed by employing a method capable of quantifying the DEP mobility of particles. Using streak-based velocimetry the particle properties are deduced from their motion in a microfluidic channel with a constant electric field gradient. From this approach, the DEP mobility of 1 μm polystyrene particles was found to be -2±0.4 10(-8)  cm4 /(V2  s). In the future, such quantitative treatment will allow for the elucidation of unique insights and rational design of devices., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High throughput screening (HTS) of our compound file provided an attractive lead compound with modest P2X(7) receptor antagonist potency and high selectivity against a panel of receptors and channels, but also with high human plasma protein binding and a predicted short half-life in humans. Multi-parameter optimization was used to address the potency, physicochemical and pharmacokinetic properties which led to potent P2X(7)R antagonists with good disposition properties. Compound 33 (CE-224,535) was advanced to clinical studies for the treatment of rheumatoid arthritis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Doxorubicin (DOX), an anthracycline used to treat a variety of cancers, is known to generate intracellular reactive oxygen species. Moreover, many patients who have undergone chemotherapy complain of cognitive dysfunction often lasting years after cessation of the chemotherapy. Previously, we reported that intraperitoneal administration of DOX led to elevated TNF-α and oxidative stress in the plasma and brain of mice. However, the mechanisms involved in nontargeted tissue damage remain unknown. In this study, we measured plasma oxidative stress and cytokine levels in patients treated with DOX. We observed increased plasma protein carbonylation and elevation of TNF-α 6 h after DOX administration in the context of multiagent chemotherapy regimens. Importantly, patients not treated coincidentally with 2-mercaptoethane sulfonate (MESNA) showed statistically significantly increased plasma protein-bound 4-hydroxynonenal, whereas those who had been coincidentally treated with MESNA as part of their multiagent chemotherapy regimen did not, suggesting that concomitant administration of the antioxidant MESNA with DOX prevents intravascular oxidative stress. We demonstrate in a murine model that MESNA suppressed DOX-induced increased plasma oxidative stress indexed by protein carbonyls and protein-bound HNE, and also suppressed DOX-induced increased peripheral TNF-α levels. A direct interaction between DOX and MESNA was demonstrated by MESNA suppression of DOX-induced DCF fluorescence. Using redox proteomics, we identified apolipoprotein A1 (APOA1) in both patients and mice after DOX administration as having increased specific carbonyl levels. Macrophage stimulation studies showed that oxidized APOA1 increased TNF-α levels and augmented TNF-α release by lipopolysaccharide, effects that were prevented by MESNA. This study is the first to demonstrate that DOX oxidizes plasma APOA1, that oxidized APOA1 enhances macrophage TNF-α release and thus could contribute to potential subsequent TNF-α-mediated toxicity, and that MESNA interacts with DOX to block this mechanism and suggests that MESNA could reduce systemic side effects of DOX., (Copyright © 2011 Elsevier Inc. All rights reserved.)