Evolution of IGF-1 in children born small for gestational age and with growth retardation, treated by growth hormone adapted to IGF-1 levels after 1 year

AIM: This study was designed to estimate the percentage of growth hormone (GH)-treated children born small for gestational age (SGA), with serum IGF-1 >2 SDS before and after GH dose adaptation. METHODS: SGA boys aged 4-9 and girls aged 4-7 with a height <-2 SDS and an annual growth rate below the mean received a subcutaneous GH dose of 57 mug/kg/day for 2 years. The GH dose was to be decreased by 30% in children with serum IGF-1 >2 SDS at 12 months and on the previous sample. The GH dose could be reduced a second time to 35 mug/kg.day. IGF-1 and IGFBP-3 dosages were centralized. RESULTS: Among the 49 (21 boys) children included in the study, 8 (16.3%) had an IGF-1 >2 SDS consecutively at 9 and 12 months (95% CI 7.3, 29.7). The GH dose was decreased in 6/8 children. However, IGF-1 levels were elevated at several nonconsecutive determinations in 45% (95% CI 28.4, 56.6) of the patients. CONCLUSION: A high IGF-1 level is observed in 45% of the GH SGA-treated children with a relatively high dose of GH. A 30% reduction in the GH dose causes a decrease in IGF-1 below 2 SDS in most children

Descent of Equivalences and Character Bijections

Categorical equivalences between block algebras of finite groups—such as Morita and derived equivalences—are well known to induce character bijections which commute with the Galois groups of field extensions. This is the motivation for attempting to realise known Morita and derived equivalences over non-splitting fields. This article presents various results on the theme of descent to appropriate subfields and subrings. We start with the observation that perfect isometries induced by a virtual Morita equivalence induce isomorphisms of centres in non-split situations and explain connections with Navarro’s generalisation of the Alperin–McKay conjecture. We show that Rouquier’s splendid Rickard complex for blocks with cyclic defect groups descends to the non-split case. We also prove a descent theorem for Morita equivalences with endopermutation source

Bayesian and Markov chain Monte Carlo methods for identifying nonlinear systems in the presence of uncertainty

In this paper, the authors outline the general principles behind an approach to Bayesian system identification and highlight the benefits of adopting a Bayesian framework when attempting to identify models of nonlinear dynamical systems in the presence of uncertainty. It is then described how, through a summary of some key algorithms, many of the potential difficulties associated with a Bayesian approach can be overcome through the use of Markov chain Monte Carlo (MCMC) methods. The paper concludes with a case study, where an MCMC algorithm is used to facilitate the Bayesian system identification of a nonlinear dynamical system from experimentally observed acceleration time histories

Pseudo-potentials and loading surfaces for an endochronic plasticity theory with isotropic damage

The endochronic theory, developed in the early 70s, allows the plastic behavior of materials to be represented by introducing the notion of intrinsic time. With different viewpoints, several authors discussed the relationship between this theory and the classical theory of plasticity. Two major differences are the presence of plastic strains during unloading phases and the absence of an elastic domain. Later, the endochronic plasticity theory was modified in order to introduce the effect of damage. In the present paper, a basic endochronic model with isotropic damage is formulated starting from the postulate of strain equivalence. Unlike the previous similar analyses, in this presentation the formal tools chosen to formulate the model are those of convex analysis, often used in classical plasticity: namely pseudopotentials, indicator functions, subdifferentials, etc. As a result, the notion of loading surface for an endochronic model of plasticity with damage is investigated and an insightful comparison with classical models is made possible. A damage pseudopotential definition allowing a very general damage evolution is given

Glutamine-to-glutamate ratio in the nucleus accumbens predicts effort-based motivated performance in humans

Substantial evidence implicates the nucleus accumbens in motivated performance, but very little is known about the neurochemical underpinnings of individual differences in motivation. Here, we applied 1H magnetic resonance spectroscopy (1H-MRS) at ultra-high-field in the nucleus accumbens and inquired whether levels of glutamate (Glu), glutamine (Gln), GABA or their ratios predict interindividual differences in effort-based motivated task performance. Given the incentive value of social competition, we also examined differences in performance under self-motivated or competition settings. Our results indicate that higher accumbal Gln-to-Glu ratio predicts better overall performance and reduced effort perception. As performance is the outcome of multiple cognitive, motor and physiological processes, we applied computational modeling to estimate best-fitting individual parameters related to specific processes modeled with utility, effort and performance functions. This model-based analysis revealed that accumbal Gln-to-Glu ratio specifically relates to stamina; i.e., the capacity to maintain performance over long periods. It also indicated that competition boosts performance from task onset, particularly for low Gln-to-Glu individuals. In conclusion, our findings provide novel insights implicating accumbal Gln and Glu balance on the prediction of specific computational components of motivated performance. This approach and findings can help developing therapeutic strategies based on targeting metabolism to ameliorate deficits in effort engagement

Determinants of Theory of Mind performance in Alzheimer’s disease: A data-mining study

Whether theory of mind (ToM) is preserved in Alzheimer’s disease (AD) remains a controversial subject. Recent studies have showed that performance on some ToM tests might be altered in AD, though to a lesser extent than in behavioural-variant Frontotemporal Dementia (bvFTD). It is however, unclear if this reflects a genuine impairment of ToM or a deficit secondary to the general cognitive decline observed in AD. Aiming to investigate the cognitive determinants of ToM performance in AD, a data-mining study was conducted in 29 AD patients then replicated in an independent age-matched group of 19 AD patients to perform an independent replication of the results. 44 bvFTD patients were included as a comparison group. All patients had an extensive neuropsychological examination. Hierarchical clustering analyses showed that ToM performance clustered with measures of executive functioning in AD. ToM performance was also specifically correlated with the executive component extracted from a principal component analysis. In a final step, automated linear modelling conducted to determine the predictors of ToM performance showed that 48.8% of ToM performance was significantly predicted by executive measures. Similar findings across analyses were observed in the independent group of AD patients, thereby replicating our results. Conversely, ToM impairments in bvFTD appeared independent of other cognitive impairments. These results suggest that difficulties of AD patients on ToM tests do not reflect a genuine ToM deficit, rather mediated by general (and particularly executive) cognitive decline. They also suggest that executive functioning has a key role in mental state attribution, which support interacting models of ToM functioning. Finally, our study highlights the relevancy of data-mining statistical approaches in clinical and cognitive neurosciences

Should I trust you? Learning and memory of social interactions in dementia

Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in individuals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a “trust game” task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social “lottery” condition was also included. Participants’ learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions

Effort and performance in a cooperative activity are boosted by perception of a partner’s effort

In everyday life, people must often determine how much time and effort to allocate to cooperative activities. In the current study, we tested the hypothesis that the perception of others’ effort investment in a cooperative activity may elicit a sense of commitment, leading people to allocate more time and effort to the activity themselves. We developed an effortful task in which participants were required to move an increasingly difficult bar slider on a screen while simultaneously reacting to the appearance of virtual coins and earn points to share between themselves and their partner. This design allowed us to operationalize commitment in terms of participants’ investment of time and effort. Crucially, the cooperative activity could only be performed after a partner had completed a complementary activity which we manipulated to be either easy (Low Effort condition) or difficult (High Effort condition). Our results revealed participants invested more effort, persisted longer and performed better in the High Effort condition, i.e. when they perceived their partner to have invested more effort. These results support the hypothesis that the perception of a partner’s effort boosts one’s own sense of commitment to a cooperative activity, and consequently also one’s willingness to invest time and effort

The self-reference effect in dementia: Differential involvement of cortical midline structures in Alzheimer’s disease and behavioural-variant frontotemporal dementia

Encoding information in reference to the self enhances subsequent memory for the source of this information. In healthy adults, self-referential processing has been proposed to be mediated by the cortical midline structures (CMS), with functional differentiation between anterior-ventral, anterior-dorsal and posterior regions. While both Alzheimer’s disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) patients show source memory impairment, it remains unclear whether they show a typical memory advantage for self-referenced materials. We also sought to identify the neural correlates of this so-called ‘self-reference effect’ (SRE) in these patient groups. The SRE paradigm was tested in AD (n=16) and bvFTD (n=22) patients and age-matched healthy controls (n=17). In this task, participants studied pictures of common objects paired with one of two background scenes (sources) under self-reference or other-reference encoding instructions, followed by an item and source recognition memory test. Voxel-based morphometry was used to investigate correlations between SRE measures and regions of grey matter atrophy in the CMS. The behavioural results indicated that self-referential encoding did not ameliorate the significant source memory impairments in AD and bvFTD patients. Furthermore, the reduced benefit of self-referential relative to other-referential encoding was not related to general episodic memory deficits. Our imaging findings revealed that reductions in the SRE were associated with atrophy in the anterior-dorsal CMS across both patient groups, with additional involvement of the posterior CMS in AD and anterior-ventral CMS in bvFTD. These findings suggest that although the SRE is comparably reduced in AD and bvFTD, this arises due to impairments in different subcomponents of self-referential processing