Examining psychopathy from an attachment perspective: the role of fear of rejection and abandonment

A key feature of psychopathy, a self-centered orientation towards others and a failure to truly connect, is poorly understood. The attachment framework can be used to examine underlying interpersonal mechanisms. Because of the overall failure to connect, we anticipated, and found, in a large undergraduate sample (n=1074) that both affective-interpersonal traits and impulsive-irresponsible psychopathy facets were positively related to attachment avoidance. Different dynamics may underlie this distancing from others, as evidenced by the fact that callous-unemotionality was negatively related to attachment anxiety, whereas grandiose-manipulative and impulsive-irresponsible traits were positively related to attachment anxiety. Although effect sizes were small and are of correlational nature, our results are in line with a dual deficit model that differential developmental trajectories, largely heritable callousness vs. neglecting and abusive parenting, may lead to adult psychopathy. The differentiating role of fear of rejection and abandonment for the psychopathy construct is discussed

The strong weak convergence of the quasi-EA

In this paper, we investigate the convergence of a novel simulation scheme to the target diffusion process. This scheme, the Quasi-EA, is closely related to the Exact Algorithm (EA) for diffusion processes, as it is obtained by neglecting the rejection step in EA. We prove the existence of a myopic coupling between the Quasi-EA and the diffusion. Moreover, an upper bound for the coupling probability is given. Consequently we establish the convergence of the Quasi-EA to the diffusion with respect to the total variation distance

Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy

<p>Abstract</p> <p>Background</p> <p>Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m²and 100 mg/m²) or weekly regimens (35–40 mg/m²). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m²docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m²regimen.</p> <p>Methods</p> <p>Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m²docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m²docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level.</p> <p>Results</p> <p>The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m².</p> <p>Conclusion</p> <p>The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m²and 100 mg/m²docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m²weekly docetaxel.</p

Clinical pharmacodynamic factors in docetaxel toxicity

Neutropenia is the main dose-limiting toxicity occurring in docetaxel treatment. The objective of this study was to identify pharmacodynamic (PD) factors responsible for the neutropaenia caused by docetaxel. Data were obtained from 92 patients treated with docetaxel as a monochemotherapy in two different treatment centres. A semiphysiological population pharmacokinetic–pharmacodynamic (PK/PD) model was applied to describe the time course of neutrophils and the neutropaenic effect of docetaxel. The plasma docetaxel concentration was assumed to inhibit the proliferation of neutrophil precursors through a linear model: Drug effect=Slope × Conc. Slope corresponds to the patients' sensitivity to the neutropaenic effect of docetaxel. Covariate analysis was performed by testing the relationship between the patients' characteristics and Slope using the program NONMEM. The neutropaenic effect of docetaxel showed a high interindividual variability. Three significant PD covariates were identified: serum α1-acid glycoprotein levels (AAG), level of chemotherapy pretreatment, and treatment centre. Extensive pretreatment was associated with an increase in Slope values meaning a higher haematotoxicity. An increase in AAG was associated with a decrease of both Slope and docetaxel plasma clearance. Patients treated in one centre had both higher Slope and docetaxel clearance. The centre effect (most likely due to a bias in the PK part of the study between the two centres) reveals the robustness of the PK/PD model. Individual dosing of docetaxel should be based on previous chemotherapy but not on the AAG level since it has a similar influence on PD and PK docetaxel parameters. This methodology should be applied to further investigate elderly patients and to identify more precisely the characteristics of previous chemotherapy that contribute to the cumulative myelotoxicity

Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients

Background: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. Methods: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). Results: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. Conclusions: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD. © 2012 Pace et al

SMART Research: Toward Interdisciplinary River Science in Europe

Interdisciplinary science is rapidly advancing to address complex human-environment interactions. River science aims to provide the methods and knowledge required to sustainably manage some of the planet’s most important and vulnerable ecosystems; and there is a clear need for river managers and scientists to be trained within an interdisciplinary approach. However, despite the science community’s recognition of the importance of interdisciplinary training, there are few studies examining interdisciplinary graduate programs, especially in science and engineering. Here we assess and reflect on the contribution of a 9-year European doctoral program in river science: ‘Science for MAnagement of Rivers and their Tidal Systems’ Erasmus Mundus Joint Doctorate (SMART EMJD). The program trained a new generation of 36 early career scientists under the supervision of 34 international experts from different disciplinary and interdisciplinary research fields focusing on river systems, aiming to transcend the boundaries between disciplines and between science and management. We analyzed the three core facets of the SMART program, namely: (1) interdisciplinarity, (2) internationalism, and (3) management-oriented science. We reviewed the contents of doctoral theses and publications and synthesized the outcomes of two questionnaire surveys conducted with doctoral candidates and supervisors. A high percentage of the scientific outputs (80%) were interdisciplinary. There was evidence of active collaboration between different teams of doctoral candidates and supervisors, in terms of joint publications (5 papers out of the 69 analyzed) but this was understandably quite limited given the other demands of the program. We found evidence to contradict the perception that interdisciplinarity is a barrier to career success as employment rates were high (97%) and achieved very soon after the defense, both in academia (50%) and the private/public sector (50%) with a strong international dimension. Despite management-oriented research being a limited (9%) portion of the ensemble of theses, employment in management was higher (22%). The SMART program also increased the network of international collaborations for doctoral candidates and supervisors. Reflections on doctoral training programs like SMART contribute to debates around research training and the career opportunities of interdisciplinary scientists

Prominent changes in cerebro-cerebellar functional connectivity during continuous cognitive processing

While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSN) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro cerebellar loops connecting the posterior cerebellum to associative cortices, remains unclear. In this study, 22 healthy volunteers underwent a multi-session functional magnetic resonance imaging (fMRI) protocol composed of four consecutive 8-min resting state fMRI (rs-fMRI) scans. After a first control scan, participants listened to a narrated story for the entire duration of the second rs-fMRI scan; two further rs-fMRI scans followed the end of story listening. The story plot was purposely designed to stimulate specific cognitive processes that are known to involve the cerebro-cerebellar loops. Almost all of the identified 15 RSNs showed changes in functional connectivity (FC) during and for several minutes after the story. The FC changes mainly occurred in the frontal and prefrontal cortices and in the posterior cerebellum, especially in Crus I-II and lobule VI. The FC changes occurred in cerebellar clusters belonging to different RSNs, including the cerebellar network (CBLN), sensory networks (lateral visual network, LVN; medial visual network, MVN) and cognitive networks (default mode network, DMN; executive control network, ECN; right and left ventral attention networks, RVAN and LVAN; salience network, SN; language network, LN; and working memory network, WMN). Interestingly, a k-means analysis of FC changes revealed clustering of FCN, ECN and WMN, which are all involved in working memory functions, CBLN, DMN and SN, which play a key-role in attention switching, and RSNs involved in visual imagery. These results show that the cerebellum is deeply entrained in well-structured network clusters, which reflect multiple aspects of cognitive processing, during and beyond the conclusion of auditory stimulation

Stability of Strong Species Interactions Resist the Synergistic Effects of Local and Global Pollution in Kelp Forests

Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO2). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO2). The positive effects of nutrient and CO2 enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities

Coping with Commitment: Projected Thermal Stress on Coral Reefs under Different Future Scenarios

BACKGROUND: Periods of anomalously warm ocean temperatures can lead to mass coral bleaching. Past studies have concluded that anthropogenic climate change may rapidly increase the frequency of these thermal stress events, leading to declines in coral cover, shifts in the composition of corals and other reef-dwelling organisms, and stress on the human populations who depend on coral reef ecosystems for food, income and shoreline protection. The ability of greenhouse gas mitigation to alter the near-term forecast for coral reefs is limited by the time lag between greenhouse gas emissions and the physical climate response. METHODOLOGY/PRINCIPAL FINDINGS: This study uses observed sea surface temperatures and the results of global climate model forced with five different future emissions scenarios to evaluate the "committed warming" for coral reefs worldwide. The results show that the physical warming commitment from current accumulation of greenhouse gases in the atmosphere could cause over half of the world's coral reefs to experience harmfully frequent (p> or =0.2 year(-1)) thermal stress by 2080. An additional "societal" warming commitment, caused by the time required to shift from a business-as-usual emissions trajectory to a 550 ppm CO(2) stabilization trajectory, may cause over 80% of the world's coral reefs to experience harmfully frequent events by 2030. Thermal adaptation of 1.5 degrees C would delay the thermal stress forecast by 50-80 years. CONCLUSIONS/SIGNIFICANCE: The results suggest that adaptation -- via biological mechanisms, coral community shifts and/or management interventions -- could provide time to change the trajectory of greenhouse gas emissions and possibly avoid the recurrence of harmfully frequent events at the majority (97%) of the world's coral reefs this century. Without any thermal adaptation, atmospheric CO(2) concentrations may need to be stabilized below current levels to avoid the degradation of coral reef ecosystems from frequent thermal stress events