Differentiating Psychopathy from General Antisociality Using the P3 as a Psychophysiological Correlate of Attentional Allocation

Recent studies have shown that while psychopathy and non-psychopathic antisociality overlap, they differ in the extent to which cognitive impairments are present. Specifically, psychopathy has been related to abnormal allocation of attention, a function that is traditionally believed to be indexed by event-related potentials (ERPs) of the P3-family. Previous research examining psychophysiological correlates of attention in psychopathic individuals has mainly focused on the parietally distributed P3b component to rare targets. In contrast, very little is known about the frontocentral P3a to infrequent novel events in psychopathy. Thus, findings on the P3 components in psychopathy are inconclusive, while results in non-psychopathic antisocial populations are clearer and point toward an inverse relationship between antisociality and P3 amplitudes. The present study adds to extant literature on the P3a and P3b in psychopathy by investigating component amplitudes in psychopathic offenders (N = 20), matched non-psychopathic offenders (N = 23) and healthy controls (N = 16). Also, it was assessed how well each offender group was able to differentially process rare novel and target events. The offender groups showed general amplitude reductions compared to healthy controls, but did not differ mutually on overall P3a/P3b amplitudes. However, the psychopathic group still exhibited normal neurophysiological differentiation when allocating attention to rare novel and target events, unlike the non-psychopathic sample. The results highlight differences between psychopathic and non-psychopathic offenders regarding the integrity of the neurocognitive processes driving attentional allocation, as well as the usefulness of alternative psychophysiological measures in differentiating psychopathy from general antisociality.     

Gene duplications contribute to the overrepresentation of interactions between proteins of a similar age

Background

Disruptive selection has been documented in a growing number of natural populations. Yet, its prevalence within individual systems remains unclear. Furthermore, few studies have sought to identify the ecological factors that promote disruptive selection in the wild. To address these issues, we surveyed 15 populations of Mexican spadefoot toad tadpoles, Spea multiplicata, and measured the prevalence of disruptive selection acting on resource-use phenotypes. We also evaluated the relationship between the strength of disruptive selection and the intensity of intraspecific competition??an ecological agent hypothesized to be an important driver of disruptive selection.

Results

Disruptive selection was the predominant mode of quadratic selection across all populations. However, a directional component of selection favoring an extreme ecomorph??a distinctive carnivore morph??was also common. Disruptive selection was strongest in populations experiencing the most intense intraspecific competition, whereas stabilizing selection was only found in populations experiencing relatively weak intraspecific competition.

Conclusions

Disruptive selection can be common in natural populations. Intraspecific competition for resources may be a key driver of such selection.     

New bispyridinium oximes: in vitro and in vivo evaluation of their biological efficiency in soman and tabun poisoning

Improving the efficacy of antidotal treatment of poisonings with nerve agents is still a challenge for the scientific community. This study investigated the interactions of four bispyridinium oximes with human erythrocyte acetylcholinesterase (AChE) and their effects on soman- and tabun-poisoned mice. Oximes HI-6 and TMB-4 were used for comparison. These oximes inhibited AchE with inhibitory potency (IC(50)) ranging from 0.02 to 1.0 mM. The best reactivating potency (%R) was obtained with K074, when AChE was inhibited by tabun. The protective potency (P(50)) of all oximes in human erythrocyte AChE inhibited by soman and tabun could not be determined. In tabun-poisoned mice very good antidotal efficacy was obtained with K027, K048, and K074, which makes them interesting for future investigation. The combination of HI-6 and atropine is the therapy of choice for soman poisoning.     

Consequences of gene targeting procedures for behavioural responses and morphological development of newborn mice

In this study the effects of gene targeting procedures on the early behaviour and morphological development of the resulting offspring have been investigated. Six groups of mice, each having undergone a specific aspect of the biotechnological procedure, (including electroporation, microinjection and/or embryo culture) and one control group, were compared. Development of behaviour, morphological characteristics and body weight of the progeny were tested daily from birth to weaning (0–3 weeks) for all groups. No significant differences in behaviour or morphological development were observed. However, the occurrence of increased (perinatal) pup mortality and increased body weight in the procedural groups, indicates that during the production of gene targeted mice, some of the normal physiological and/or developmental processes can be affected. Therefore, gene targeting procedures should always be accompanied by careful monitoring of health and welfare of the resulting offspring.     

Identifying Predictors of Activity Based Anorexia Susceptibility in Diverse Genetic Rodent Populations

Animal studies are very useful in detection of early disease indicators and in unravelling the pathophysiological processes underlying core psychiatric disorder phenotypes. Early indicators are critical for preventive and efficient treatment of progressive psychiatric disorders like anorexia nervosa. Comparable to physical hyperactivity observed in anorexia nervosa patients, in the activity-based anorexia rodent model, mice and rats express paradoxical high voluntary wheel running activity levels when food restricted. Eleven inbred mouse strains and outbred Wistar WU rats were exposed to the activity-based anorexia model in search of identifying susceptibility predictors. Body weight, food intake and wheel running activity levels of each individual mouse and rat were measured. Mouse strains and rats with high wheel running activity levels during food restriction exhibited accelerated body weight loss. Linear mixed models for repeated measures analysis showed that baseline wheel running activity levels preceding the scheduled food restriction phase strongly predicted activity-based anorexia susceptibility (mice: Beta  =  −0.0158 (±0.003 SE), P<0.0001; rats: Beta  =  −0.0242 (±0.004 SE), P<0.0001) compared to other baseline parameters. These results suggest that physical activity levels play an important role in activity-based anorexia susceptibility in different rodent species with genetically diverse background. These findings support previous retrospective studies on physical activity levels in anorexia nervosa patients and indicate that pre-morbid physical activity levels could reflect an early indicator for disease severity.     

17 years of grassland management leads to parallel local and regional biodiversity shifts among a wide range of taxonomic groups

Conservation management is expected to increase local biodiversity, but uniform management may lead to biotic homogenization and diversity losses at the regional scale. We evaluated the effects of renewed grazing and cutting management carried out across a whole region, on the diversity of plants and seven arthropod groups. Changes in occurrence over 17 years of intensive calcareous grassland management were analysed at the species level, which gave insight into the exact species contributing to regional homogenization or differentiation. Reponses were compared between species differing in habitat affinity, dispersal ability, food specialisation and trophic level. Local species richness increased over the sampling period for true bugs and millipedes, while carabid beetles and weevils declined in local species richness. Species richness remained unchanged for plants, woodlice, ants and spiders. Regional diversity and compositional variation generally followed local patterns. Diversity shifts were only to a limited extent explained by species’ habitat affinity, dispersal ability, trophic level and food specialisation. We conclude that implementation of relatively uniform conservation management across a region did not lead to uniform changes in local species composition. This is an encouraging result for conservation managers, as it shows that there is not necessarily a conflict of interest between local and regional conservation goals. Our study also demonstrates that shifts in diversity patterns differ markedly between taxonomic groups. Single traits provide only limited understanding of these differences. This highlights the need for a wide taxonomic scope when evaluating conservation management and demonstrates the need to understand the mechanisms underlying occurrence shifts.     

Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

Background

Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT) augmentation therapy on emphysema progression using CT densitometry.

Methods

Data from these similar trials, a 2-center Danish-Dutch study (n = 54) and the 3-center EXAcerbations and CT scan as Lung Endpoints (EXACTLE) study (n = 65), were pooled to increase the statistical power. The change in 15^th percentile of lung density (PD15) measured by CT scan was obtained from both trials. All subjects had 1 CT scan at baseline and at least 1 CT scan after treatment. Densitometric data from 119 patients (AAT [Alfalastin^® or Prolastin^®], n = 60; placebo, n = 59) were analysed by a statistical/endpoint analysis method. To adjust for lung volume, volume correction was made by including the change in log-transformed total lung volume as a covariate in the statistical model.

Results

Mean follow-up was approximately 2.5 years. The mean change in lung density from baseline to last CT scan was -4.082 g/L for AAT and -6.379 g/L for placebo with a treatment difference of 2.297 (95% CI, 0.669 to 3.926; p = 0.006). The corresponding annual declines were -1.73 and -2.74 g/L/yr, respectively.

Conclusions

The overall results of the combined analysis of 2 separate trials of comparable design, and the only 2 controlled clinical trials completed to date, has confirmed that IV AAT augmentation therapy significantly reduces the decline in lung density and may therefore reduce the future risk of mortality in patients with AAT deficiency-related emphysema.

Trial registration

The EXACTLE study was registered in ClinicalTrials.gov as ''Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients''; ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00263887","term_id":"NCT00263887"}}NCT00263887.     

Effect of deep inspiration avoidance on ventilation heterogeneity and airway responsiveness in healthy adults

The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways (P = 0.02) but did not affect convection-dependent airways (P = 0.9). DI avoidance increased both airway closure (P = 0.002) and airway narrowing (P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing (r(s) = 0.14) or airway closure (r(s) = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.     

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00626080","term_id":"NCT00626080"}}NCT00626080.