Two-transcript gene expression classifiers in the diagnosis and prognosis of human diseases.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Identification of molecular classifiers from genome-wide gene expression analysis is an important practice for the investigation of biological systems in the post-genomic era--and one with great potential for near-term clinical impact. The 'Top-Scoring Pair' (TSP) classification method identifies pairs of genes whose relative expression correlates strongly with phenotype. In this study, we sought to assess the effectiveness of the TSP approach in the identification of diagnostic classifiers for a number of human diseases including bacterial and viral infection, cardiomyopathy, diabetes, Crohn's disease, and transformed ulcerative colitis. We examined transcriptional profiles from both solid tissues and blood-borne leukocytes. RESULTS: The algorithm identified multiple predictive gene pairs for each phenotype, with cross-validation accuracy ranging from 70 to nearly 100 percent, and high sensitivity and specificity observed in most classification tasks. Performance compared favourably with that of pre-existing transcription-based classifiers, and in some cases was comparable to the accuracy of current clinical diagnostic procedures. Several diseases of solid tissues could be reliably diagnosed through classifiers based on the blood-borne leukocyte transcriptome. The TSP classifier thus represents a simple yet robust method to differentiate between diverse phenotypic states based on gene expression profiles. CONCLUSION: Two-transcript classifiers have the potential to reliably classify diverse human diseases, through analysis of both local diseased tissue and the immunological response assayed through blood-borne leukocytes. The experimental simplicity of this method results in measurements that can be easily translated to clinical practice

The Relationship between Marital Status and Psychological Resilience in Chronic Pain

We examined the relationship between marital status and a 2-stage model of pain-related effect, consisting of pain unpleasantness and suffering. We studied 1914 chronic pain patients using multivariate analysis of covariance (MANCOVA) to clarify whether marital status was a determinant factor in the emotional or ideational suffering associated with chronic pain after controlling for pain sensation intensity, age, and ethnicity. Marital status was unrelated to immediate unpleasantness (). We found a strong association with emotional suffering () but not with negative illness beliefs (). Interestingly, widowed subjects experienced significantly less frustration, fear, and anger than all other groups (married, divorced, separated, or single). A final MANCOVA including sex as a covariate revealed that the emotional response to pain was the same for both widow and widower. Only those individuals whose spouse died experienced less emotional turmoil in the face of a condition threatening their lifestyle. These data suggest that after experiencing the death of a spouse, an individual may derive some “emotional inoculation” against future lifestyle threat

Experimental Bounds on Masses and Fluxes of Nontopological Solitons

We have re-analyzed the results of various experiments which were not originally interested as searches for the Q-ball or the Fermi-ball. Based on these analyses, in addition to the available data on Q-balls, we obtained rather stringent bounds on flux, mass and typical energy scale of Q-balls as well as Fermi-balls. In case these nontopological solitons are the main component of the dark matter of the Galaxy, we found that only such solitons with very large quantum numbers are allowed. We also estimate how sensitive future experiments will be in the search for Q-balls and Fermi-balls.Comment: 19 pages, 7 eps figures, RevTeX, psfig.st

Circumstellar Structure around Evolved Stars in the Cygnus-X Star Formation Region

We present observations of newly discovered 24 micron circumstellar structures detected with the Multiband Imaging Photometer for Spitzer (MIPS) around three evolved stars in the Cygnus-X star forming region. One of the objects, BD+43 3710, has a bipolar nebula, possibly due to an outflow or a torus of material. A second, HBHA 4202-22, a Wolf-Rayet candidate, shows a circular shell of 24 micron emission suggestive of either a limb-brightened shell or disk seen face-on. No diffuse emission was detected around either of these two objects in the Spitzer 3.6-8 micron Infrared Array Camera (IRAC) bands. The third object is the luminous blue variable candidate G79.29+0.46. We resolved the previously known inner ring in all four IRAC bands. The 24 micron emission from the inner ring extends ~1.2 arcmin beyond the shorter wavelength emission, well beyond what can be attributed to the difference in resolutions between MIPS and IRAC. Additionally, we have discovered an outer ring of 24 micron emission, possibly due to an earlier episode of mass loss. For the two shell stars, we present the results of radiative transfer models, constraining the stellar and dust shell parameters. The shells are composed of amorphous carbon grains, plus polycyclic aromatic hydrocarbons in the case of G79.29+0.46. Both G79.29+0.46 and HBHA 4202-22 lie behind the main Cygnus-X cloud. Although G79.29+0.46 may simply be on the far side of the cloud, HBHA 4202-22 is unrelated to the Cygnus-X star formation region.Comment: Accepted by A

A systematic review on the effects of group singing on persistent pain in people with long‐term health conditions

Singing can have a range of health benefits; this paper reviews the evidence of the effects of group singing for chronic pain in people with long‐term health conditions. We searched for published peer‐reviewed singing studies reporting pain measures (intensity, interference and depression) using major electronic databases (last search date 31 July 2018). After screening 123 full texts, 13 studies met the inclusion criteria: five randomized controlled trials (RCTs), seven non‐RCTs and one qualitative study. Included studies were appraised using Downs and Black and the Critical Appraisals Skills Programme quality assessments. Included studies reported differences in the type of singing intervention, long‐term condition and pain measures. Due to the high heterogeneity, we conducted a narrative review. Singing interventions were found to reduce pain intensity in most studies, but there was more equivocal support for reducing pain interference and depression. Additionally, qualitative data synthesis identified three key linked and complementary themes: physical, psychological and social benefits. Group singing appears to have the potential to reduce pain intensity, pain interference and depression; however, we conclude that there is only partial support for singing on some pain outcomes based on the limited available evidence of varied quality. Given the positive findings of qualitative studies, this review recommends that practitioners are encouraged to continue this work. More studies of better quality are needed. Future studies should adopt more robust methodology and report their singing intervention in details. Group singing may be an effective and safe approach for reducing persistent pain and depression in people with long‐term health conditions.Health and Social Care Research Centr

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Supplement 75 Personal non-commercial use only

In our review, the neurobiology of fibromyalgia syndrome (FM) is discussed in the context of what is known about neural mechanisms of nociception and central mechanisms of persistent pain conditions. We present a general view of mechanisms of nociception, central temporal summation, and central sensitization, and as well compare sensory tests that examine these mechanisms in normal pain-free human subjects. We then show how amplification and other alterations of these mechanisms apply to patients with FM. NOCICEPTION, ACUTE PAIN, PERSISTENT PAIN Pain is usually related to impulse input that originates from nociceptors in somatic or visceral tissues. The impulses travel in myelinated (A-delta) and unmyelinated (C) peripheral nerves, which first project to dorsal horn nociceptor-specific neurons and wide dynamic range neurons, before these second-order neurons transmit nociceptive information to brain regions involved in pain, including the thalamus, anterior cingulate cortex (ACC), anterior insular cortex, and somatosensory cortex. Nociceptor-specific neurons are so termed because they respond predominantly to specific stimulus intensities that either cause tissue damage or would cause tissue damage if maintained over time. Wide dynamic range neurons respond differentially over a very broad range of stimulus intensities, from very gentle touch to stimuli that cause tissue damage. Brain regions that receive input from nociceptor-specific and wide dynamic range neurons are related to sensory-discriminative, cognitive-evaluative, and affective processing of somatosensory nociceptive input. The activation of these brain regions is associated with pain experience and subsequent reflex and protective behaviors. Importantly, the same brain areas are likely to be involved in both acute and persistent pain conditions. Reflex and reflective behaviors that are aimed at eliminating acute pain are not operative in chronic pain syndromes including FM. Patients with FM, like most chronic pain sufferers, do not display pain behaviors usually seen in acute pain, including increased perspiration, hypertension, hyperthermia, and tachycardia. FM patients have abnormal pain thresholds (hyperalgesia) and report amplified pain with a variety of nociceptive stimuli, including pressure, heat, and cold. Because no consistent tissue abnormalities have been detected in FM, central pain processing abnormalities need to be considered as important contributors to the heightened pain sensitivity of these patients. In our review, we also discuss recent evidence that the clinical pain of patients with FM is related to abnormal central temporal summation of pain, or "windup," evoked by repetitive stimulation of peripheral nociceptive afferent neurons. Sensory testing experiments can be used to demonstrate that abnormal windup of FM patients is related to central nervous system (CNS) mechanisms of central sensitization and persistent pain. As background to the central sensory abnormalities of FM patients, we discuss the normal role of nociceptors and the central consequences of repetitive stimulation of nociceptive neurons, and also describe how these mechanisms appear to be distorted in FM patients. DONALD D. PRICE and ROLAND STAUD ABSTRACT. Accumulating evidence suggests that fibromyalgia syndrome (FM) pain is maintained by tonic impulse input from deep tissues, such as muscle and joints, in combination with central sensitization mechanisms. This nociceptive input may originate in peripheral tissues (trauma and infection) resulting in hyperalgesia/allodynia and/or central sensitization. Evidence for abnormal sensitization mechanisms in FM includes enhanced temporal summation of delayed pain in response to repeated heat taps and repeated muscle taps, as well as prolonged and enhanced painful after-sensations in FM patients but not control subjects. Moreover, magnitudes of enhanced after-sensations are predictive of FM patients' ongoing clinical pain. Such alterations of relevant pain mechanisms may lead to longterm neuroplastic changes that exceed the antinociceptive capabilities of affected individuals, resulting in ever-increasing pain sensitivity and dysfunction. Future research needs to address the important role of abnormal nociception and/or antinociception for chronic pain in FM. (J Rheumatol 2005;32 Suppl 75:22-28

Massive stars in the giant molecular cloud G23.3−0.3 and W41

Context. Young massive stars and stellar clusters continuously form in the Galactic disk, generating new Hii regions within their natal giant molecular clouds and subsequently enriching the interstellar medium via their winds and supernovae.Aims. Massive stars are among the brightest infrared stars in such regions; their identification permits the characterisation of the star formation history of the associated cloud as well as constraining the location of stellar aggregates and hence their occurrence as a function of global environment.Methods. We present a stellar spectroscopic survey in the direction of the giant molecular cloud G23.3−0.3. This complex is located at a distance of ~4–5 kpc, and consists of several Hii regions and supernova remnants.Results. We discovered 11 OfK+ stars, one candidate luminous blue variable, several OB stars, and candidate red supergiants. Stars with K-band extinction from ~1.3–1.9 mag appear to be associated with the GMC G23.3−0.3; O and B-types satisfying this criterion have spectrophotometric distances consistent with that of the giant molecular cloud. Combining near-IR spectroscopic and photometric data allowed us to characterize the multiple sites of star formation within it. The O-type stars have masses from ~25–45 M⊙, and ages of 5–8 Myr. Two new red supergiants were detected with interstellar extinction typical of the cloud; along with the two RSGs within the cluster GLIMPSE9, they trace an older burst with an age of 20–30 Myr. Massive stars were also detected in the core of three supernova remnants – W41, G22.7−0.2, and G22.7583−0.4917.Conclusions. A large population of massive stars appears associated with the GMC G23.3−0.3, with the properties inferred for them indicative of an extended history of stars formation

The Balloon-Borne Large Aperture Submillimeter Telescope (BLAST) 2005: A 10 deg^2 Survey of Star Formation in Cygnus X

We present Cygnus X in a new multi-wavelength perspective based on an unbiased BLAST survey at 250, 350, and 500 micron, combined with rich datasets for this well-studied region. Our primary goal is to investigate the early stages of high mass star formation. We have detected 184 compact sources in various stages of evolution across all three BLAST bands. From their well-constrained spectral energy distributions, we obtain the physical properties mass, surface density, bolometric luminosity, and dust temperature. Some of the bright sources reaching 40 K contain well-known compact H II regions. We relate these to other sources at earlier stages of evolution via the energetics as deduced from their position in the luminosity-mass (L-M) diagram. The BLAST spectral coverage, near the peak of the spectral energy distribution of the dust, reveals fainter sources too cool (~ 10 K) to be seen by earlier shorter-wavelength surveys like IRAS. We detect thermal emission from infrared dark clouds and investigate the phenomenon of cold ``starless cores" more generally. Spitzer images of these cold sources often show stellar nurseries, but these potential sites for massive star formation are ``starless" in the sense that to date there is no massive protostar in a vigorous accretion phase. We discuss evolution in the context of the L-M diagram. Theory raises some interesting possibilities: some cold massive compact sources might never form a cluster containing massive stars; and clusters with massive stars might not have an identifiable compact cold massive precursor.Comment: 42 pages, 31 Figures, 6 table