Stroke Survivors Who Score below Threshold on Standard Depression Measures May Still Have Negative Cognitions of Concern

Background and Purpose— There has been an increase in screening for depression in the physically ill. We explored whether important negative cognitions may be missed by conventional approaches to screening for depression in 2 independently conducted stroke studies with similar methods. Methods— The Auckland Regional Community Stroke (ARCOS) study was a prospective, population-based stroke incidence study conducted in Auckland, New Zealand, for 12 months in 2002 to 2003. The Stroke Outcomes Study was a prospective, hospital cohort study conducted in Leeds and Bradford, United Kingdom, for 33 months in 2002 to 2005. Symptoms of abnormal mood were assessed at 6 months in ARCOS with a single simple question, “Do you often feel sad and depressed?” and the 28-item General Health Questionnaire administered as part of a structured interview and in the Stroke Outcomes Study with the 28-item General Health Questionnaire and a single question about depressed mood taken from the Present State Examination. Results— Mood data were available at 6 months from 770 ARCOS and 492 Stroke Outcomes Study participants. A significant proportion (up to 28%) of people who did not meet study criteria for depression reported important negative cognitions such as hopelessness, worthlessness, or suicidality. People who were older, dependent in activities of daily living, or not partnered were more likely to report negative cognitions. Conclusions— Important negative cognitions, including suicidal thoughts, may be missed when people are screened for depression after stroke. Screening alone is not an adequate substitute for a sensitive exploration of the psychological impact of stroke on the survivor

Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction

Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity

Fermentation kinetics including product and substrate inhibitions plus biomass death: a mathematical analysis

Fermentation is generally modelled by kinetic equations giving the time evolutions for biomass, substrate, and product concentrations. Although these equations can be solved analytically in simple cases if substrate/product inhibition and biomass death are included, they are typically solved numerically. We propose an analytical treatment of the kinetic equations --including cell death and an arbitrary number of inhibitions-- in which constant yield needs not be assumed. Equations are solved in phase space, i.e. the biomass concentration is written explicitly as a function of the substrate concentration.Comment: 4 pages, 4 figure

Ionospheric electrons in Titan's tail: Plasma structure during the cassini T9 encounter

We present results from the CAPS electron spectrometer obtained during the downstream flyby of Titan on 26 December 2005, which occurred during a period of enhanced plasma pressure inside the magnetosphere. The electron data show an unusual split signature with two principal intervals of interest outside the nominal corotation wake. Interval 1 shows direct evidence for ionospheric plasma escape at several RT in Titan's tail. Interval 2 shows a complex plasma structure, a mix between plasma of ionospheric and magnetospheric origin. We suggest a mechanism for plasma escape based on ambipolar electric fields set up by suprathermal ionospheric photoelectrons

Spontaneous Parity Violation in SUSY Strong Gauge Theory

We suggest simple models of spontaneous parity violation in supersymmetric strong gauge theory. We focus on left-right symmetric model and investigate vacuum with spontaneous parity violation. Non-perturbative effects are calculable in supersymmetric gauge theory, and we suggest two new models. The first model shows confinement, and the second model has a dual description of the theory. The left-right symmetry breaking and electroweak symmetry breaking are simultaneously occurred with the suitable energy scale hierarchy. The second model also induces spontaneous supersymmetry breaking.Comment: 14 page

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p <\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

A New Class of Small Molecule Inhibitor of BMP Signaling

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development

On the gauge boson's properties in a candidate technicolor theory

The technicolor scenario replaces the Higgs sector of the standard model with a strongly interacting sector. One candidate for a realization of such a sector is two-technicolor Yang-Mills theory coupled to two degenerate flavors of adjoint, massless techniquarks. Using lattice gauge theory the properties of the technigluons in this scenario are investigated as a function of the techniquark mass towards the massless limit. For that purpose the minimal Landau gauge two-point and three-point correlation functions are determined, including a detailed systematic error analysis. The results are, within the relatively large systematic uncertainties, compatible with a behavior very similar to QCD at finite techniquark mass. However, the limit of massless techniquarks exhibits features which could be compatible with a (quasi-)conformal behavior.Comment: 27 pages, 17 figures, 1 table; v2: persistent notational error corrected, some minor modification

Craniectomy size for subdural haematomas and the impact on brain shift and outcomes

BACKGROUND: Midline shift in trauma relates to the severity of head injury. Large craniectomies are thought to help resolve brain shift but can be associated with higher rates of morbidity. This study explores the relationship between craniectomy size and subtemporal decompression for acute subdural haematomas with the resolution of brain compression and outcomes. No systematic study correlating these measures has been reported. METHOD: A retrospective study of all adult cases of acute subdural haematomas that presented to a Major Trauma Centre and underwent a primary decompressive craniectomy between June 2008 and August 2013. Data collection included patient demographics and presentation, imaging findings and outcomes. All imaging metrics were measured by two independent trained assessors. Compression was measured as midline shift, brainstem shift and cisternal effacement. RESULTS: Thirty-six patients with mean age of 36.1 ± 12.5 (range 16-62) were included, with a median follow-up of 23.5 months (range 2.2-109.6). The median craniectomy size was 88.7 cm2 and the median subtemporal decompression was 15.0 mm. There was significant post-operative resolution of shift as measured by midline shift, brainstem shift and cisternal effacement score (all p < .00001). There was no mortality, and the majority of patients made a good recovery with 82.8% having a Modified Rankin Score of 2 or less. There was no association between craniectomy size or subtemporal decompression and any markers of brain shift or outcome (all R2 < 0.05). CONCLUSIONS: This study suggests that there is no clear relationship between craniectomy size or extent of subtemporal decompression and resolution of brain shift or outcome. Further studies are needed to assess the relative efficacy of large craniectomies and the role of subtemporal decompression

Super-GZK Photons from Photon-Axion Mixing

We show that photons with energies above the GZK cutoff can reach us from very distant sources if they mix with light axions in extragalactic magnetic fields. The effect which enables this is the conversion of photons into axions, which are sufficiently weakly coupled to travel large distances unimpeded. These axions then convert back into high energy photons close to the Earth. We show that photon-axion mixing facilitates the survival of super-GZK photons most efficiently with a photon-axion coupling scale of order 10^11 GeV, which is in the same range as the scale for the photon-axion mixing explanation for the dimming of supernovae without cosmic acceleration. We discuss possible observational consequences of this effect.Comment: 17 pages, 5 figures. Published versio