The prevalence and burden of subthreshold generalized anxiety disorder: A systematic review

Background: To review the prevalence and impact of generalized anxiety disorder (GAD) below the diagnostic threshold and explore its treatment needs in times of scarce healthcare resources.Methods: A systematic literature search was conducted until January 2013 using PUBMED/MEDLINE, PSYCINFO, EMBASE and reference lists to identify epidemiological studies of subthreshold GAD, i.e. GAD symptoms that do not reach the current thresholds of DSM-III-R, DSM-IV or ICD-10. Quality of all included studies was assessed and median prevalences of subthreshold GAD were calculated for different subpopulations.Results: Inclusion criteria led to 15 high-quality and 3 low-quality epidemiological studies with a total of 48,214 participants being reviewed. Whilst GAD proved to be a common mental health disorder, the prevalence for subthreshold GAD was twice that for the full syndrome. Subthreshold GAD is typically persistent, causing considerably more suffering and impairment in psychosocial and work functioning, benzodiazepine and primary health care use, than in non-anxious individuals. Subthreshold GAD can also increase the risk of onset and worsen the course of a range of comorbid mental health, pain and somatic disorders; further increasing costs. Results are robust against bias due to low study quality.Conclusions: Subthreshold GAD is a common, recurrent and impairing disease with verifiable morbidity that claims significant healthcare resources. As such, it should receive additional research and clinical attention. © 2014 Haller et al.; licensee BioMed Central Ltd

Compositional analysis of InAs-GaAs-GaSb heterostructures by low-loss electron energy loss spectroscopy

As an alternative to Core-Loss Electron Energy Loss Spectroscopy, Low-Loss EELS is suitable for compositional analysis of complex heterostructures, such as the InAs-GaAs-GaSb system, since in this energy range the edges corresponding to these elements are better defined than in Core-Loss. Furthermore, the analysis of the bulk plasmon peak, which is present in this energy range, also provides information about the composition. In this work, compositional information in an InAs-GaAs-GaSb heterostructure has been obtained from Low-Loss EEL spectra

Polyhedral Analysis using Parametric Objectives

The abstract domain of polyhedra lies at the heart of many program analysis techniques. However, its operations can be expensive, precluding their application to polyhedra that involve many variables. This paper describes a new approach to computing polyhedral domain operations. The core of this approach is an algorithm to calculate variable elimination (projection) based on parametric linear programming. The algorithm enumerates only non-redundant inequalities of the projection space, hence permits anytime approximation of the output

Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions

Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression

Massive Schwinger model and its confining aspects on curved space-time

Using a covariant method to regularize the composite operators, we obtain the bosonized action of the massive Schwinger model on a classical curved background. Using the solution of the bosonic effective action, the energy of two static external charges with finite and large distance separation on a static curved space-time is obtained. The confining behavior of this model is also explicitly discussed.Comment: A disscussion about the infrared regularization and also two references are added. Accepted for publication in Phys. Rev. D (2001

Electrostatic self-energy and Bekenstein entropy bound in the massive Schwinger model

We obtain the electrostatic energy of two opposite charges near the horizon of stationary black-holes in the massive Schwinger model. Besides the confining aspects of the model, we discuss the Bekenstein entropy upper bound of a charged object using the generalized second law. We show that despite the massless case, in the massive Schwinger model the entropy of the black hole and consequently the Bekenstein bound are altered by the vacuum polarization.Comment: 14 pages, accepted for publication in "Gen. Rel. Grav. (2005)

Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom

Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Soft systems methodology: a context within a 50-year retrospective of OR/MS

Soft systems methodology (SSM) has been used in the practice of operations research and management science OR/MS) since the early 1970s. In the 1990s, it emerged as a viable academic discipline. Unfortunately, its proponents consider SSM and traditional systems thinking to be mutually exclusive. Despite the differences claimed by SSM proponents between the two, they have been complementary. An extensive sampling of the OR/MS literature over its entire lifetime demonstrates the richness with which the non-SSM literature has been addressing the very same issues as does SSM