Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity.

Cognitive-behavioral therapy (CBT) is effective for obsessive compulsive disorder (OCD); however, little is understood about its mechanisms related to brain network connectivity. We examined connectivity changes from resting-state functional magnetic resonance imaging data pre-to-post-CBT in 43 OCD participants, randomized to receive either 4 weeks of intensive CBT or 4 weeks waitlist followed by 4 weeks of CBT, and 24 healthy controls before and after 4 weeks of no treatment. Network-based-statistic analysis revealed large-magnitude increases in OCD connectivity in eight networks. Strongest increases involved connectivity between the cerebellum and caudate/putamen, and between the cerebellum and dorsolateral/ventrolateral prefrontal cortices. Connectivity increases were associated with increased resistance to compulsions. Mechanisms of CBT may involve enhanced cross-network integration, both within and outside of classical cortico-striatal-thalamo-cortical regions; those involving cerebellar to striatal and prefrontal regions may reflect acquisition of new non-compulsive goal-directed behaviors and thought patterns. Our findings have implications for identifying targets for enhancing treatment efficacy and monitoring treatment progress

Finding and Resolving Security Misusability with Misusability Cases

Although widely used for both security and usability concerns, scenarios used in security design may not necessarily inform the design of usability, and vice- versa. One way of using scenarios to bridge security and usability involves explicitly describing how design deci- sions can lead to users inadvertently exploiting vulnera- bilities to carry out their production tasks. This paper describes how misusability cases, scenarios that describe how design decisions may lead to usability problems sub- sequently leading to system misuse, address this problem. We describe the related work upon which misusability cases are based before presenting the approach, and illus- trating its application using a case study example. Finally, we describe some findings from this approach that further inform the design of usable and secure systems

British Society of Echocardiography guideline for the transthoracic echocardiographic assessment of cardiac amyloidosis

These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK

Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis

Bowling Together: Scientific Collaboration Networks of Demographers at European Population Conferences

Studies of collaborative networks of demographers are relatively scarce. Similar studies in other social sciences provide insight into scholarly trends of both the fields and characteristics of their successful scientists. Exploiting a unique database of metadata for papers presented at six European Population Conferences, this report explores factors explaining research collaboration among demographers. We find that (1) collaboration among demographers has increased over the past 10 years, however, among co-authored papers, collaboration across institutions remains relatively unchanged over the period, (2) papers based on core demographic subfields such as fertility, mortality, migration and data and methods are more likely to involve multiple authors and (3) multiple author teams that are all female are less likely to co-author with colleagues in different institutions. Potential explanations for these results are discussed alongside comparisons with similar studies of collaboration networks in other related social sciences

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.</p> <p>Methods</p> <p>Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.</p> <p>Results</p> <p>Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.</p

Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report

<p>Abstract</p> <p>Background</p> <p>Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases.</p> <p>Case Presentation</p> <p>We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP) gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrP^res) in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI.</p> <p>Conclusions</p> <p>In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG), genetic analysis, and nuclear imaging may aid in diagnosis.</p

Increased ion temperature and neutron yield observed in magnetized indirectly driven D_{2}-filled capsule implosions on the national ignition facility

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9  kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3  μs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment