Previous theory and research on the structural, longitudinal, and genetic nature of psychopathy have provided strong conceptual and empirical evidence that overt antisociality is a component of the ...psychopathy construct (Hare & Neumann, 2008, 2010; Lynam & Miller, 2012). However, determination of the strength of the association between antisociality and other psychopathic features has not been explored systematically. The current article draws on previously published large North American studies, as well as data from across the globe, to estimate the strength and pattern of the associations between overt antisociality and other psychopathic domains in a diverse set of samples. Structural equation modeling was used to estimate model parameters from samples that had data on either the Psychopathy Checklist‐Instruments (PCL‐R, PCL: YV, PCL: SV) or self‐report assessments that have known latent structures (SRP, B‐Scan 360). In addition, two relatively large samples (male offenders and young adult males), assessed with both the PCL‐R and the SRP, provided an opportunity to examine the link between antisociality and the other psychopathy domains across different assessment methods. The overall findings indicate that the associations were moderate to strong, depending on the nature of the sample, and clearly indicate that antisociality is a core component of the psychopathy construct.
In this review, we focus on two major influences on current conceptualizations of psychopathy: one clinical, with its origins largely in the early case studies of Cleckley, and the other empirical, ...the result of widespread use of the Hare Psychopathy Checklist-Revised (PCL-R) for assessment purposes. Some investigators assert that the PCL-R, ostensibly based on Cleckley's work, has "drifted" from the construct described in his Clinical Profile. We evaluate this profile, note its basis in an unrepresentative sample of patients, and suggest that its literal and uncritical acceptance by the research community has become problematical. We also argue that the idea of construct "drift" is irrelevant to current conceptualizations of psychopathy, which are better informed by the extensive empirical research on the integration of structural, genetic, developmental, personality, and neurobiological research findings than by rigid adherence to early clinical formulations. We offer some suggestions for future research on psychopathy.
Metabolomic data are frequently acquired using chromatographically coupled mass spectrometry (MS) platforms. For such datasets, the first step in data analysis relies on feature detection, where a ...feature is defined by a mass and retention time. While a feature typically is derived from a single compound, a spectrum of mass signals is more a more-accurate representation of the mass spectrometric signal for a given metabolite. Here, we report a novel feature grouping method that operates in an unsupervised manner to group signals from MS data into spectra without relying on predictability of the in-source phenomenon. We additionally address a fundamental bottleneck in metabolomics, annotation of MS level signals, by incorporating indiscriminant MS/MS (idMS/MS) data implicitly: feature detection is performed on both MS and idMS/MS data, and feature–feature relationships are determined simultaneously from the MS and idMS/MS data. This approach facilitates identification of metabolites using in-source MS and/or idMS/MS spectra from a single experiment, reduces quantitative analytical variation compared to single-feature measures, and decreases false positive annotations of unpredictable phenomenon as novel compounds. This tool is released as a freely available R package, called RAMClustR, and is sufficiently versatile to group features from any chromatographic-spectrometric platform or feature-finding software.
Numerous studies conducted with offender
or forensic psychiatric samples have revealed that
individuals with psychopathic traits are at risk for
violence and other externalizing psychopathology. ...These
traits appear to be continuously distributed in these
samples, leading investigators to speculate on the presence
of such traits in the general population. Nonetheless, few
studies of psychopathy have been conducted with large random
samples of individuals from the community. The community
sample from the MacArthur Violence Risk Assessment Study
provides an opportunity to examine the prevalence and
structural nature of psychopathic traits, as well as their
association with external correlates in an urban community.
The community data (
N
= 514) represent a
stratified random sample of persons between the ages of 18
and 40 who were assessed on the Psychopathy Checklist:
Screening Version (PCL: SV) and also for violent behavior,
alcohol use, and intellectual functioning. Structural
equation model analyses revealed that a 4-factor model found
in offender and forensic psychiatric samples fit the
community data well and was invariant across sex and
ethnicity. Also, a superordinate factor comprehensively
accounted for the 4 psychopathy first-order factors and
significantly predicted the external correlates. The
findings offer insight into the dimensional nature of the
psychopathy construct.
Although a disturbance in empathy has been related to all personality traits comprising the Dark Tetrad (i.e. Machiavellianism, narcissism, psychopathy, sadism), the relationship between different ...aspects of empathy and these dark traits measured jointly has not been empirically scrutinised. Therefore, the aim of the present study was to examine the associations between the Dark Tetrad, the two-dimensional (cognitive vs affective) model of empathy, and the ability to recognize emotions. Participants (N=576; 250 males) for this online study were recruited using the snowball sampling method via social networking sites. Results revealed that all personality traits were inversely related to both affective and cognitive empathy, except for a positive correlation between narcissism and cognitive empathy. The regression analyses showed that the unique aspects of the Dark Triad negatively predicted affective empathy, whereas only Machiavellianism (negatively) and narcissism (positively) predicted cognitive empathy. Although both psychopathy and sadism were inversely correlated with the performance in the emotion recognition task, only sadism remained as a significant negative predictor once the shared variance was accounted for. The findings established different empathic profiles of each dark trait, thus supporting the construct of the Dark Tetrad as a set of overlapping, yet distinctive traits.
•All Dark Tetrad traits were negatively associated with affective empathy.•Sadism, psychopathy and Machiavellianism were inversely linked to cognitive empathy.•Affective empathy was negatively predicted by the Dark Triad traits.•Cognitive empathy was predicted by narcissism and Machiavellianism.•Emotion recognition was negatively predicted by sadism.
J. Skeem and D. J. Cooke (2010)
asserted that Hare and Neumann consider criminality to be an essential component of the psychopathy construct. The assertion, presented in the guise of a debate on the ...nature of psychopathy, is neither accurate nor consistent with the clinical and empirical literature on psychopathy to which Hare and Neumann have contributed. Broadly defined antisociality, not criminality per se, is considered to be part of the psychopathy construct. Skeem and Cooke also expressed concerns that the popularity of the Psychopathy Checklist-Revised (
R. D. Hare, 2003
) inhibits the development and use of other instruments, that it has become the construct it measures, that it deviates from its clinical roots, and that it conflates criminality with personality. These and related issues are addressed, and it is suggested that the arguments proffered by Skeem and Cooke are not convincing, nor do they provide clear directions for theory and research.
Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB ...efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.
This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria.
ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5–41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5–94.9, P = 0.004).
This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.
Drug delivery systems (DDS) that allow spatially and temporally controlled release of drugs are of particular interest in the field of drug delivery. These systems create opportunities for ...individually tailored doses of drugs to be administered as well as reduce side effects by localizing the initial drug dose to the organ of interest. We present an electroresponsive DDS in the form of a bioresorbable nanocomposite film which operates at low voltages (<-2 V). The method is based on electrochemically generating local pH changes at an electrode surface to induce dissolution of a pH-sensitive polymer, which is used as the carrier material. We previously demonstrated this proof-of-concept using a poly(methyl methacrylate-co-methacrylic acid) (co-PMMA) copolymer commercially marketed as Eudragit S100 (EGT). However, as EGT is soluble at a pH above 7, experiments were performed in isotonic saline solutions (pH ∼ 6.4). In this work, we have synthesized co-PMMA with a variety of monomer ratios to shift the solubility of the copolymer to higher pH values, and developed a polymer that can be used under physiologically relevant conditions. The generalizability of this system was demonstrated by showing controlled release of different drug molecules with varying parameters like size, hydrophobicity, and pKa. Fluorescein, a hydrophilic model compound, meloxicam, a hydrophobic anti-arthritic medication, curcumin, a small molecule with anti-cancer therapeutic potential, and insulin, a polypeptide hormone used in the treatment of hypoglycemia, could all be released on demand with minimal leakage. The drug loading achieved was ∼32 wt% by weight of the co-polymer.
Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) ...and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
OS data were available for 912 patients. The median PFS was 3.3months (95% CI 2.9–3.6) and 6-month PFS rate was 27% (95% CI 24–30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3cm versus <3cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2months (95% CI 9.5–11.0) and 1year OS was 43% (95% CI 40–47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
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