Exploring the cognitive correlates of boredom in traumatic brain injury (TBI).

Boredom is a common human experience, yet little is known about its underlying neural mechanisms. This thesis first set out to investigate the construct of boredom and more closely examined its relationship to phenomenologically similar mood states of depression, apathy and anhedonia. Next, deficits in sustained attention, and novelty seeking were examined in patients with traumatic brain injury (TBI), who are characterized by atypically high levels of boredom. Study 1 established that although related to varying degrees to apathy, anhedonia, and depression, boredom is indeed a distinct emotional experience. Furthermore, two boredom proneness subtypes - agitated and apathetic - were identified which varied in their relationships to depression. The relationship between boredom and depression was found to be high only in the agitated boredom prone subtype, which is characterised by a high degree of motivation to engage in meaningful, stimulating activities despite the fact that all attempts to do so fail to satisfy. In Study 2, the relationship between boredom proneness and depression was found to be greater in TBI patients than in healthy controls. Using a behavioral measure of sustained attention (SART; Robertson et al., 1997), Study 3 demonstrated a relationship between boredom proneness and sustained attention in healthy controls, such that RTs were faster and commission errors more prevalent in the agitated boredom prone subtype. No relationship between boredom proneness and sustained attention was found in TBI patients. So while attention and boredom show a clear relationship in the healthy brain, this relationship may be disrupted in TBI patients. Finally, Study 4 demonstrated an association between agitated boredom proneness and a preference for novel stimuli across participant groups. In addition, patients had a poorer ability to discriminate between similar and dissimilar stimuli than controls, which was more evident in the agitated boredom prone group. It may be the case then that agitated boredom prone individuals fail to satisfy their desire to engage in stimulating activities in part because they fail to accurately identify when something is indeed novel. Taken together, these results highlight important distinctions between apathetic and agitated boredom proneness, and the way in which these subtypes relate to depression, attention, and novelty seeking, in brain injured patients and healthy controls. More work is needed to determine the role played by boredom in TBI, particularly as this evolves from acute to chronic stages of the illness. Importantly, identifying boredom as a key element in depressive mood disorders, attention deficits (e.g., attention deficit hyperactivity disorder), and novelty seeking behaviour, facilitates the design and implementation of appropriate intervention strategies. For example, it will become increasingly important to deal with boredom as a significant component of depression. Thus, the work presented here represents a novel and important contribution to the study of boredom in that it brings the field one step closer to understanding and treating the experience. Further investigation with greater numbers of patients is necessary to fully explicate the relationship between boredom and depression, attention, and novelty seeking in TBI.1 yea

Establishing the Construct of Boredom as Distinct From Apathy, Anhedonia and Depression

Boredom is a common human experience that has received little attention in the literature. To date, researchers have been unable to agree on a unified theory and definition of the construct. The present study investigated the nature of boredom by exploring its relationship to three phenomenologically similar affective states, namely apathy, anhedonia and depression. Structural equation modeling revealed that although related to apathy, anhedonia and depression to varying degrees, boredom is an empirically distinct construct. Establishing boredom as an independent construct provides an important first step in bringing the field closer to a universally accepted definition of boredom, which will undoubtedly facilitate more effective assessment and treatment of the experience of boredom, particularly in individuals with psychopathological and neuropathological illnesses in which boredom is a pervasive symptom

A Novel System to Diagnose Cutaneous Adverse Drug Reactions Employing the Cellscan—Comparison with Histamine Releasing Test and Inf-γ Releasing Test

Background: There are several mechanisms to describe allergic drug reactions yet the methods to diagnose them are limited

The GUT Scale and Superpartner Masses from Anomaly Mediated Supersymmetry Breaking

We consider models of anomaly-mediated supersymmetry breaking (AMSB) in which the grand unification (GUT) scale is determined by the vacuum expectation value of a chiral superfield. If the anomaly-mediated contributions to the potential are balanced by gravitational-strength interactions, we find a model-independent prediction for the GUT scale of order $M_{\rm Planck} / (16\pi^2)$. The GUT threshold also affects superpartner masses, and can easily give rise to realistic predictions if the GUT gauge group is asymptotically free. We give an explicit example of a model with these features, in which the doublet-triplet splitting problem is solved. The resulting superpartner spectrum is very different from that of previously considered AMSB models, with gaugino masses typically unifying at the GUT scale.Comment: 17 page

Update on genetic predisposition to colorectal cancer and polyposis

The present article summarizes recent developments in the characterization of genetic predisposition to colorectal cancer (CRC). The main themes covered include new hereditary CRC and polyposis syndromes, non-CRC hereditary cancer genes found mutated in CRC patients, strategies used to identify novel causal genes, and review of candidate genes that have been proposed to predispose to CRC and/or colonic polyposis. We provide an overview of newly described genes and syndromes associated with predisposition to CRC and polyposis, including: polymerase proofreading-associated polyposis, NTHL1-associated polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations as a rare cause of hereditary nonpolyposis CRC. The implementation of next generation sequencing approaches for genetic testing has exposed the presence of pathogenic germline variants in genes associated with hereditary cancer syndromes not traditionally linked to CRC, which may have an impact on genetic testing, counseling and surveillance. The identification of new hereditary CRC and polyposis genes has not deemed an easy endeavor, even though known CRC-related genes explain a small proportion of the estimated familial risk. Whole-genome sequencing may offer a technology for increasing this proportion, particularly if applied on pedigree data allowing linkage type of analysis. The final section critically surveys the large number of candidate genes that have been recently proposed for CRC predisposition

N-methyl-D-aspartate receptor antibody-mediated neurological disease:results of a UK-based surveillance study in children

OBJECTIVE: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. DESIGN: A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. RESULTS: Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. CONCLUSIONS: Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery

Constitutional mismatch repair deficiency–associated brain tumors: report from the European C4CMMRD consortium

Abstract Background Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment. Methods Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017. Results Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1–40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19–45) and 22% (95% CI: 12–37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families). Conclusions Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches