Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy.

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects.FundingGalderma International S.A.S., Paris, France

Mental imagery in bipolar affective disorder versus unipolar depression: Investigating cognitions at times of ‘positive’ mood

AbstractBackgroundCompared to unipolar depression (UD), depressed mood in bipolar disorder (BD) has been associated with amplified negative mental imagery of the future (‘flashforwards’). However, imagery characteristics during positive mood remain poorly explored. We hypothesise first, that unlike UD patients, the most significant positive images of BD patients will be ‘flashforwards’ (rather than past memories). Second, that BD patients will experience more frequent (and more ‘powerful’) positive imagery as compared to verbal thoughts and third, that behavioural activation scores will be predicted by imagery variables in the BD group.MethodsBD (n=26) and UD (n=26) patients completed clinical and trait imagery measures followed by an Imagery Interview and a measure of behavioural activation.ResultsCompared to UD, BD patients reported more ‘flashforwards’ compared to past memories and rated their ‘flashforwards’ as more vivid, exciting and pleasurable. Only the BD group found positive imagery more ‘powerful’, (preoccupying, ‘real’ and compelling) as compared to verbal thoughts. Imagery-associated pleasure predicted levels of drive and reward responsiveness in the BD group.LimitationsA limitation in the study was the retrospective design. Moreover pathological and non-pathological periods of “positive” mood were not distinguished in the BD sample.ConclusionsThis study reveals BD patients experience positive ‘flashforward’ imagery in positive mood, with more intense qualities than UD patients. This could contribute to the amplification of emotional states and goal directed behaviour leading into mania, and differentiate BD from UD

The role of Independent Reviewing Officers (IROs) in England: final report

Independent Reviewing Officers (IROs) were introduced to represent the interests of looked after children following a number of cases where care plans had not been implemented, leading to harm. Their role was strengthened through the introduction of statutory guidance in April 2011 but there has been continuing scepticism about whether they are making enough difference to the quality of the service and whether their independence is compromised by being under local authority control. The aim of this study, undertaken by NCB Research Centre in partnership with the Centre for Child and Family Research, Loughborough University, and funded by the Nuffield Foundation, is to provide an evidence base about the way the role actually operates in order to inform future policy and practice. The research involved: national surveys of IROs, their managers and Directors of Children Services (DCSs); analysis of inquiries from IROs to independent advice services; an analysis of resources need for the IRO service; case studies of four local authorities, including analysis of care plans, interviews and focus groups with IROs, social workers, other key professionals and looked after children. The question of how the effectiveness of the IRO service can be measured is, however, complex. In their thematic inspection of the IRO role within ten local authorities published in 2013, Ofsted suggested that IROs were still not making enough positive impact. The House of Lords Committee on Adoption Reform (2013) recommended that it was time to employ IROs outside the local authority but the Government did not agree and are committed to making the role work within the current arrangements. The challenges faced by IROs are even greater now than when statutory guidance was introduced in 20111 Creating the right context . It is hoped that the evidence afforded by this study will inform the debate about how to maximise the effectiveness of the role to ensure that looked after children get the independent support they need and deserve

On the Feasibility of Malware Authorship Attribution

There are many occasions in which the security community is interested to discover the authorship of malware binaries, either for digital forensics analysis of malware corpora or for thwarting live threats of malware invasion. Such a discovery of authorship might be possible due to stylistic features inherent to software codes written by human programmers. Existing studies of authorship attribution of general purpose software mainly focus on source code, which is typically based on the style of programs and environment. However, those features critically depend on the availability of the program source code, which is usually not the case when dealing with malware binaries. Such program binaries often do not retain many semantic or stylistic features due to the compilation process. Therefore, authorship attribution in the domain of malware binaries based on features and styles that will survive the compilation process is challenging. This paper provides the state of the art in this literature. Further, we analyze the features involved in those techniques. By using a case study, we identify features that can survive the compilation process. Finally, we analyze existing works on binary authorship attribution and study their applicability to real malware binaries.Comment: FPS 201

Value beyond view: illuminating the human benefits of the ocean twilight zone

Hoagland, Porter; Jin, Di; Holland, Michael; Kostel, Ken; Taylor, Eric; Renier, Natalie; Holmes, Mark. 2019. Value beyond view: illuminating the human benefits of the ocean twilight zone. Woods Hole Oceanographic Institution, 35 pp.The twilight zone is a fundamental part of the ocean ecosystem, playing an important role in carbon sequestration and marine food webs and supporting the natural function of many planetary processes. Ecosystem services provided by the twilight zone are highly beneficial to humans, but they occur largely out of sight and they are undervalued by society as a result. To better evaluate the benefits that the twilight zone provides, an ecosystem service framework provides a way to organize our thinking about them and even to quantify their economic value. With this information at hand, leaders and policymakers can think more carefully about what we stand to gain or lose from actions that affect the twilight zone and the broader ocean environment to which it is tightly linked, particularly as we strive for the sustainable use of marine resources. The title was changed from "Ecosystem Services of the Mesopelagic" to "Value beyond view: illuminating the human benefits of the ocean twilight zone.

Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivity

The 5-HT2C receptor has been implicated in mood and eating disorders. In general, it is accepted that 5-HT2C receptor agonists increase anxiety behaviours and induce hypophagia. However, pharmacological analysis of the roles of these receptors is hampered by the lack of selective ligands and the complex regulation of receptor isoforms and expression levels. Therefore, the exact role of 5-HT2C receptors in mood disorders remain controversial, some suggesting agonists and others suggesting antagonists may be efficacious antidepressants, while there is general agreement that antagonists are beneficial anxiolytics. In order to test the hypothesis that increased 5-HT2C receptor expression, and thus increased 5-HT2C receptor signalling, is causative in mood disorders, we have undertaken a transgenic approach, directly altering the 5-HT2C receptor number in the forebrain and evaluating the consequences on behaviour. Transgenic mice overexpressing 5-HT2C receptors under the control of the CaMKIIα promoter (C2CR mice) have elevated 5-HT2C receptor mRNA levels in cerebral cortex and limbic areas (including the hippocampus and amygdala), but normal levels in the hypothalamus, resulting in > 100% increase in the number of 5-HT2C ligand binding sites in the forebrain. The C2CR mice show increased anxiety-like behaviour in the elevated plus-maze, decreased wheel-running behaviour and reduced activity in a novel environment. These behaviours were observed in the C2CR mice without stimulation by exogenous ligands. Our findings support a role for 5-HT2C receptor signalling in anxiety disorders. The C2CR mouse model offers a novel and effective approach for studying disorders associated with 5-HT2C receptors

Topology of Vibro-Impact Systems in the Neighborhood of Grazing

The grazing bifurcation is considered for the Newtonian model of vibro-impact systems. A brief review on the conditions, sufficient for existence of a grazing family of periodic solutions, is given. The properties of these periodic solutions are discussed. A plenty of results on the topological structure of attractors of vibro-impact systems is known. However, since the considered system is strongly nonlinear, these attractors may be invisible or, at least, very sensitive to changes of parameters of the system. On the other hand, they are observed in experiments and numerical simulations. We offer (Theorem 2) an approach which allows to explain this contradiction and give a new robust mathematical model of the non-hyperbolic dynamics in the neighborhood of grazing.Comment: Submitted to Physica

Age-related differences in exercise and quality of life among breast cancer survivors

Purpose: Physical activity has become a focus of cancer recovery research as it has the potential to reduce treatment-related burden and optimize health-related quality of life (HRQoL). However, the potential for physical activity to influence recovery may be age-dependent. This paper describes physical activity levels and HRQoL among younger and older women after surgery for breast cancer and explores the correlates of physical inactivity. Methods: A population-based sample of breast cancer patients diagnosed in South-East Queensland, Australia, (n=287) were assessed once every three months, from 6 to 18 months post-surgery. The Functional Assessment of Cancer Therapy-Breast questionnaire (FACTB+4) and items from the Behavioral Risk Factor Surveillance System (BRFSS) questionnaire were used to measure HRQoL and physical activity, respectively. Physical activity was assigned metabolic equivalent task (MET) values, and categorized as 3, p<0.05). Conclusions: Age influences the potential to observe HRQoL benefits related to physical activity participation. These results also provide relevant information for the design of exercise interventions for breast cancer survivors and highlights that some groups of women are at greater risk of long-term sedentary behavior

Self-images in the present and future: Role of affect and the bipolar phenotype

Background Bipolar Spectrum Disorder (BPSD) is associated with changes in self-related processing and affect, yet the relationship between self-image and affect in the BPSD phenotype is unclear. Methods 47 young adults were assessed for hypomanic experiences (BPSD phenotype) using the Mood Disorders Questionnaire. Current and future self-images (e.g. I am… I will be…) were generated and rated for emotional valence, stability, and (for future self-images only) certainty. The relationship between self-image ratings and measures of affect (depression, anxiety and mania) were analysed in relation to the BPSD phenotype. Results The presence of the BPSD phenotype significantly moderated the relationship between (1) affect and stability ratings for negative self-images, and (2) affect and certainty ratings for positive future self-images. Higher positivity ratings for current self-images were associated with lower depression and anxiety scores. Limitations This was a non-clinical group of young adults sampled for hypomanic experiences, which limits the extension of the work to clinical levels of psychopathology. This study cannot address the causal relationships between affect, self-images, and BPSD. Future work should use clinical samples and experimental mood manipulation designs. Conclusions BPSD phenotype can shape the relationship between affect and current and future self-images. This finding will guide future clinical research to elucidate BPSD vulnerability mechanisms and, consequently, the development of early interventions

Commissioning of the CSC Level 1 Trigger Optical Links at CMS

The Endcap Muon (EMU) Cathode Strip Chamber (CSC) detector at the CMS experiment at CERN has been fully installed and operational since summer of 2008. The system of 180 optical links connects the middle and upper levels of the CSC Level 1 Trigger chain. Design and commissioning of all optical links present several challenges, including reliable clock distribution, link synchronization and alignment, status monitoring and system testing. We gained an extensive experience conducting various tests, participating in local and global cosmic runs and in initial stage of the LHC operation. In this paper we present our hardware, firmware and software solutions and first results of the optical link commissioning