Prenatal FGFR2 Signaling via PI3K/AKT Specifies the PDGFRA+ Myofibroblast.

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.

Identification of neural stem and progenitor cell subpopulations using DC insulator-based dielectrophoresis.

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.

Comparing the Functioning of Youth and Adult Partnerships for Health Promotion.

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.

Religion and intergroup conflict: findings from the Global Group Relations Project.

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.

Identifying indoor environmental patterns from bioaerosol material using HPLC.

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.

Exploring the feasibility of bioaerosol analysis as a novel fingerprinting technique.

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.

Dielectrophoretic mobility determination in DC insulator-based dielectrophoresis.

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.

Risk Communication After Health Care Exposures: An Experimental Vignette Survey With Patients.

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.

Factors Associated With Access to and Receipt of Liver Transplantation in Veterans With End-stage Liver Disease.

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.

Characterization of particle capture in a sawtooth patterned insulating electrokinetic microfluidic device.

Here we present a scheme to separate particles according to their characteristic physical properties, including size, charge, polarizability, deformability, surface charge mobility, dielectric features, and local capacitance. Separation is accomplished using a microdevice based on direct current insulator gradient dielectrophoresis that can isolate and concentrate multiple analytes simultaneously at different positions. The device is dependent upon dielectrophoretic and electrokinetic forces incorporating a global longitudinal direct current field as well as using shaped insulating features within the channel to induce local gradients. This design allows for the production of strong local field gradients along a global field causing particles to enter, initially transported through the channel by electrophoresis and electroosmosis (electrokinetics), and to be isolated via repulsive dielectrophoretic forces that are proportional to an exponent of the field gradient. Sulfate-capped polystyrene nano and microparticles (20, 200 nm, and 1 µm) were used as probes to demonstrate the influence of channel geometry and applied longitudinal field on separation behavior. These results are consistent with models using similar channel geometry and indicate that specific particulate species can be isolated within a distinct portion of the device, whereas concentrating particles by factors from 10(3) to 10(6).

Development, Validation, and Evaluation of a Simple Machine Learning Model to Predict Cirrhosis Mortality.

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.

Ontology-based metabolomics data integration with quality control.

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.

Hg(II)...Pd(II) metallophilic interactions.

Reaction of bis(pentafluorophenyl)mercury (1) with the Pd(II) complexes [Pd(salophen)] (I, salophen = N,N'-disalicylidene-o-phenylenediaminate) and [Pd(N--C)(OAc)]2 (II, N--C = (2-(2-pyridyl)phenyl-C,N)) leads to the formation of the supramolecular complexes [1-(I)2] and [1-(II)2] in which the mercury synthon is sandwiched by two molecules of the palladium complex. These complexes, whose formation can be observed in solution by UV-vis spectroscopy, have been fully characterized. The short Hg-Pd distances of 3.2841(2) A in [1-(I)2] and 3.1065(8) A in [1-(II)2] indicate the presence of a Hg-Pd metallophilic interaction which, at least for [1-(II)2], is complemented by a Pd(II)-->Hg(II) donor-or component.

Subjects adjust criterion on errors in perceptual decision tasks.

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

A stochastic adding machine and complex dynamics.

This paper considers properties of a Markov chain on the natural numbers which models a binary adding machine in which there a non-zero probability of failure each time a register attempts to increment the succeeding register and resets. This chain has a family of natural quotient Markov chains, and extends naturally to a chain on the 2-adic integers. The transition operators of these chains have a self-similar structure, and have a spectrum which is, variously, the Julia set or filled Julia set of a quadratic map of the complex plane.

Fluoride ion complexation by a B(2)/Hg heteronuclear tridentate Lewis acid.

The reaction of [Li(THF)(4)][1,8-mu-(Mes(2)B)C(10)H(6)] with HgCl(2) affords [1,1'-(Hg)-[8-(Mes(2)B)C(10)H(6)](2)] () or [1-(ClHg)-8-(Mes(2)B)C(10)H(6)] (), depending on the stoichiometry of the reagents. These two new compounds have been characterized by (1)H, (13)C, (11)B and (199)Hg NMR, elemental analysis and X-ray crystallography. The cyclic voltammogram of in THF shows two distinct waves observed at E(1/2) -2.31 V and -2.61 V, corresponding to the sequential reductions of the two boron centers. Fluoride titration experiments monitored by electrochemistry suggest that binds tightly to one fluoride anion and more loosely to a second one. Theses conclusions have been confirmed by a UV-vis titration experiment which indicates that the first fluoride binding constant (K(1)) is greater than 10(8) M(-1) while the second (K(2)) equals 5.2 (+/- 0.4) x 10(3) M(-1). The fluoride binding properties of have been compared to those of [1-(Me(2)B)-8-(Mes(2)B)C(10)H(6)] () and [1-((2,6-Me(2)-4-Me(2)NC(6)H(2))Hg)-8-(Mes(2)B)C(10)H(6)] (). Both experimental and computational results indicate that its affinity for fluoride anions is comparable to that of but significantly lower than that of the diborane . In particular, the fluoride binding constants of , and in chloroform are respectively equal to 5.0 (+/- 0.2) x 10(5) M(-1), 1.0 (+/- 0.2) x 10(3) M(-1) and 1.7 (+/- 0.1) x 10(3) M(-1). Determination of the crystal structures of the fluoride adducts [S(NMe(2))(3)][-mu(2)-F] and [S(NMe(2))(3)][-mu(2)-F] along with computational results indicate that the higher fluoride binding constant of arises from a strong chelate effect involving two fluorophilic boron centers.

Structural and photophysical studies of phenanthrene adducts involving C6F5HgCl and [o-C6F4Hg]3.

Both pentafluorophenylmercury chloride and trimeric perfluoro-ortho-phenylene mercury interact with phenanthrene to form phosphorescent adducts which exhibit extended binary stacks in the solid state.