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We explore the ways in which residents of Neolithic Çatalhöyük in Anatolia differentiated themselves as well as the ways in which they did not. We integrate numerous data sets in order to assess patterns of inequality (A) across buildings with contemporaneous occupations, (B) between buildings that did or did not burn at abandonment, and (C) through time. We use Gini coefficients so as to maximize comparability with other studies of inequality in the ancient and modern worlds, discussing the underlying data and our results to clarify and enhance the value of the quantitative analyses. We evaluate whether or not trajectories of inequality align across data sets in order to determine how far success in one realm correlated with success in another. Our results indicate no unified trajectory of inequality through time. We perceive broadly similar access to staple foods, but not to goods less directly related to survival; relatively elevated income inequality during the middle portion of the site's occupation, plausibly deliberately tamped down; and no evidence for institutionalized or lasting economic or social inequality. These findings shed light on Neolithic social dynamics and also contribute to broader discussions of inequality and the social ramifications of early agropastoralism.

We explore the ways in which residents of Neolithic Çatalhöyük in Anatolia differentiated themselves as well as the ways in which they did not. We integrate numerous data sets in order to assess patterns of inequality (A) across buildings with contemporaneous occupations, (B) between buildings that did or did not burn at abandonment, and (C) through time. We use Gini coefficients so as to maximize comparability with other studies of inequality in the ancient and modern worlds, discussing the underlying data and our results to clarify and enhance the value of the quantitative analyses. We evaluate whether or not trajectories of inequality align across data sets in order to determine how far success in one realm correlated with success in another. Our results indicate no unified trajectory of inequality through time. We perceive broadly similar access to staple foods, but not to goods less directly related to survival; relatively elevated income inequality during the middle portion of the site's occupation, plausibly deliberately tamped down; and no evidence for institutionalized or lasting economic or social inequality. These findings shed light on Neolithic social dynamics and also contribute to broader discussions of inequality and the social ramifications of early agropastoralism. [ABSTRACT FROM AUTHOR]

BACKGROUND:The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis. METHODS:Case-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression. RESULTS:Mean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for 'poor anticoagulation', i.e. TTR

[This corrects the article DOI: 10.1371/journal.pone.0232354.].

The present study investigated whether measurable verbal differences occur when people vocalize their true and false intentions. To test potential differences, we used an experimental set-up where liars planned a criminal act (i.e., installing a virus on a network computer) and truth-tellers a non-criminal act (i.e., installing a new presentation program "SlideDog" on a network computer). Before they could carry out these acts, a confederate intercepted the participant and interviewed them about their intentions and the planning phase by using both anticipated and unanticipated questions. Liars used a cover story to mask their criminal intentions while truth-tellers told the entire truth. In contrast to our hypotheses, both human and automated coding did not show any evidence that liars and truth-tellers differed in plausibility or detailedness. Furthermore, results showed that asking unanticipated questions resulted in lengthier answers than anticipated questions. These results are in line with the mixed findings in the intention literature and suggest that plausibility and detailedness are less diagnostic cues for deception about intentions.

Meta-analytic findings indicate that the success of unmasking a deceptive interaction relies more on the performance of the liar than on that of the lie detector. Despite this finding, the lie characteristics and strategies of deception that enable good liars to evade detection are largely unknown. We conducted a survey (n = 194) to explore the association between laypeople's self-reported ability to deceive on the one hand, and their lie prevalence, characteristics, and deception strategies in daily life on the other. Higher self-reported ratings of deception ability were positively correlated with self-reports of telling more lies per day, telling inconsequential lies, lying to colleagues and friends, and communicating lies via face-to-face interactions. We also observed that self-reported good liars highly relied on verbal strategies of deception and they most commonly reported to i) embed their lies into truthful information, ii) keep the statement clear and simple, and iii) provide a plausible account. This study provides a starting point for future research exploring the meta-cognitions and patterns of skilled liars who may be most likely to evade detection.

BackgroundSeveral antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).MethodsMale Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.ResultsPTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.ConclusionTreatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

The aim of this study is to investigate livestock husbandry and its relationship to the mobilization of domestic animals for slaughter at large communal feasting events, in Late Neolithic Makriyalos, northern Greece. A multi-isotope approach is built that integrates analysis of: δ13C and δ15N values of human and animal bone collagen for understanding long-term dietary behavior,Incremental δ13C and δ18O values of domestic animal tooth enamel carbonate for assessing seasonal patterns in grazing habits and mobility, and87Sr/86Sr ratios of cattle tooth enamel for examining the possibility that some of the animals consumed at the site were born outside the local environment. The findings indicate that cattle had isotopically more variable diets than sheep, which may reflect grazing over a wider catchment area in the local landscape. Cattle products did not make a significant contribution to the long-term dietary protein intake of the humans, which may indicate that they were primarily consumed during episodic feasting events. There is no indication that pasturing of livestock was pre-determined by their eventual context of slaughter (i.e. large-scale feasting vs. more routine consumption events). Two non-local cattle identified among those deposited in a feasting context may have been brought to the site as contributions to these feasts. The evidence presented provides a more detailed insight into local land use and into the role of livestock and feasting in forging social relationships within the regional human population.

The present study investigated the beliefs of students and police officers about cues to deception. A total of 95 police officers and 104 undergraduate students filled out a questionnaire addressing beliefs about cues to deception. Twenty-eight verbal cues were included in the questionnaire, all extracted from verbal credibility assessment tools (i.e., CBCA, RM, and SCAN). We investigated to what extent beliefs about nonverbal and verbal cues of deception differed between lay people (students) and police officers, and whether these beliefs were in agreement with objective cues known from research. Both students and police officers believed the usual stereotypical, but non-diagnostic (nonverbal) cues such as gaze aversion and increased movement to be indicative of deception. Yet, participants were less inclined to overestimate the relationship between verbal cues and deception and their beliefs fitted better with what we know from research. The implications of these findings for practice are discussed.

In a large study on early crop water management, stable carbon isotope discrimination was determined for 275 charred grain samples from nine archaeological sites, dating primarily to the Neolithic and Bronze Age, from the Eastern Mediterranean and Western Asia. This has revealed that wheat (Triticum spp.) was regularly grown in wetter conditions than barley (Hordeum sp.), indicating systematic preferential treatment of wheat that may reflect a cultural preference for wheat over barley. Isotopic analysis of pulse crops (Lens culinaris, Pisum sativum and Vicia ervilia) indicates cultivation in highly varied water conditions at some sites, possibly as a result of opportunistic watering practices. The results have also provided evidence for local land-use and changing agricultural practices.

ObjectiveTo determine the genetic contribution to leukocyte endothelial adhesion.MethodsLeukocyte endothelial adhesion was assessed through a novel cell-based assay using human lymphoblastoid cell lines. A high-throughput screening method was developed to evaluate the inter-individual variability in leukocyte endothelial adhesion using lymphoblastoid cell lines derived from different donors. To assess heritability, ninety-two lymphoblastoid cell lines derived from twenty-three monozygotic twin pairs and twenty-three sibling pairs were compared. These lymphoblastoid cell lines were plated with the endothelial cell line EA.hy926 and labeled with Calcein AM dye. Fluorescence was assessed to determine endothelial cell adhesion to each lymphoblastoid cell line. Intra-pair similarity was determined for monozygotic twins and siblings using Pearson pairwise correlation coefficients.ResultsA leukocyte endothelial adhesion assay for lymphoblastoid cell lines was developed and optimized (CV = 8.68, Z'-factor = 0.67, SNR = 18.41). A higher adhesion correlation was found between the twins than that between the siblings. Intra-pair similarity for leukocyte endothelial adhesion in monozygotic twins was 0.60 compared to 0.25 in the siblings. The extent to which these differences are attributable to underlying genetic factors was quantified and the heritability of leukocyte endothelial adhesion was calculated to be 69.66% (p-valueConclusionsThere is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion.

Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students' credits and student retention - something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology's potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective.

Successful curative treatment of severe pulmonary arterial hypertension with luminal obliteration will require a thorough understanding of the mechanism underlying the development and progression of pulmonary vascular lesions. But the cells that obliterate the pulmonary arterial lumen in severe pulmonary arterial hypertension are incompletely characterized. The goal of our study was to evaluate whether inhibition of CXC chemokine receptor 4 will prevent the accumulation of c-kit⁺ cells and severe pulmonary arterial hypertension. We detected c-kit⁺⁻ cells expressing endothelial (von Willebrand Factor) or smooth muscle cell/myofibroblast (α-smooth muscle actin) markers in pulmonary arterial lesions of SU5416/chronic hypoxia rats. We found increased expression of CXC chemokine ligand 12 in the lung tissue of SU5416/chronic hypoxia rats. In our prevention study, AMD3100, an inhibitor of the CXC chemokine ligand 12 receptor, CXC chemokine receptor 4, only moderately decreased pulmonary arterial obliteration and pulmonary hypertension in SU5416/chronic hypoxia animals. AMD3100 treatment reduced the number of proliferating c-kit⁺ α-smooth muscle actin⁺ cells and pulmonary arterial muscularization and did not affect c-kit⁺ von Willebrand Factor⁺ cell numbers. Both c-kit⁺ cell types expressed CXC chemokine receptor 4. In conclusion, our data demonstrate that in the SU5416/chronic hypoxia model of severe pulmonary hypertension, the CXC chemokine receptor 4-expressing c-kit⁺ α-smooth muscle actin⁺ cells contribute to pulmonary arterial muscularization. In contrast, vascular lumen obliteration by c-kit⁺ von Willebrand Factor⁺ cells is largely independent of CXC chemokine receptor 4.

INTRODUCTION: Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent changes in these exercise variables reflect improvements in survival. The aim of this study was to determine changes in exercise variables in PAH patients and to relate these changes to survival. METHODS: Baseline cardiopulmonary exercise test (CPET) variables and six-minute-walk-distance (6MWD) were available from 65 idiopathic PAH patients (50 females; mean age 45±2yrs). The same variables were determined after treatment (13months) in a sub group of 43 patients. To estimate the association between changes in exercise variables and changes in cardiac function, right-ventricle ejection fraction (RVEF) was measured by cardiac MRI at baseline and after treatment in 34 patients. Mean follow-up time after the second CPET was 53 (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to baseline and treatment-associated changes in exercise variables. RESULTS: Survivors showed a significantly greater change in maximal oxygen uptake than non-survivors and this change in aerobic capacity was significantly related to changes in RVEF. From baseline until the end of the study period, two patients underwent a lung transplantation and 19 patients died. Survival analysis showed that baseline 6MWD (p

INTRODUCTION: When hemoptysis complicates pulmonary arterial hypertension (PAH), it is assumed to result from bronchial artery hypertrophy. In heritable PAH, the most common mutation is in the BMPR2 gene, which regulates growth, differentiation and apoptosis of mesenchymal cells. The aim of this study is to determine the relationship in PAH between the occurrence of hemoptysis, and disease progression, bronchial artery hypertrophy, pulmonary artery dilation and BMPR2 mutations. METHODS: 129 IPAH patients underwent baseline pulmonary imaging (CT angio or MRI) and repeated right-sided heart catheterization. Gene mutations were assessed in a subset of patients. RESULTS: Hemoptysis was associated with a greater presence of hypertrophic bronchial arteries and more rapid hemodynamic deterioration. The presence of a BMPR2 mutation did not predispose to the development of hemoptysis, but was associated with a greater number of hypertrophic bronchial arteries and a worse baseline hemodynamic profile. CONCLUSION: Hemoptysis in PAH is associated with bronchial artery hypertrophy and faster disease progression. Although the presence of a BMPR2 mutation did not correlate with a greater incidence of hemoptysis in our patient cohort, its association with worse hemodynamics and a trend of greater bronchial arterial hypertrophy may increase the risk of hemoptysis.

Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1α was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1α and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1α, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1α. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1α protein expression via activation of sphingosine kinase 1; as a consequence, S1P salvages fenretinide induced emphysema in rat lungs.

Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1α) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK).To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA).Copper depletion caused emphysematous changes, decreased HIF-1α activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim.These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1α and FAK activity in the lung.

INTRODUCTION: It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure. METHODS: Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output. RESULTS: Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure. CONCLUSIONS: We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.

BackgroundCardiac remodelling after AMI is characterized by molecular and cellular mechanisms involving both the ischemic and non-ischemic myocardium. The extent of right ventricular (RV) dilatation and dysfunction and its relation to pulmonary hypertension (PH) following AMI are unknown. The aim of the current study was to evaluate changes in dimensions and function of the RV following acute myocardial infarction (AMI) involving the left ventricle (LV).MethodsWe assessed changes in RV dimensions and function 1 week following experimental AMI involving the LV free wall in 10 mice and assessed for LV and RV dimensions and function and for the presence and degree of PH.ResultsRV fractional area change and tricuspidal annular plane systolic excursion significantly declined by 33% (P = 0.021) and 28% (P = 0.001) respectively. Right ventricular systolic pressure measured invasively in the mouse was within the normal values and unchanged following AMI.ConclusionAMI involving the LV and sparing the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse indicating that RV dysfunction developed independent of changes in RV afterload.