Utility of multispectral imaging for nuclear classification of routine clinical histopathology imagery

<p>Abstract</p> <p>Background</p> <p>We present an analysis of the utility of multispectral versus standard RGB imagery for routine H&E stained histopathology images, in particular for pixel-level classification of nuclei. Our multispectral imagery has 29 spectral bands, spaced 10 nm within the visual range of 420–700 nm. It has been hypothesized that the additional spectral bands contain further information useful for classification as compared to the 3 standard bands of RGB imagery. We present analyses of our data designed to test this hypothesis.</p> <p>Results</p> <p>For classification using all available image bands, we find the best performance (equal tradeoff between detection rate and false alarm rate) is obtained from either the multispectral or our "ccd" RGB imagery, with an overall increase in performance of 0.79% compared to the next best performing image type. For classification using single image bands, the single best multispectral band (in the red portion of the spectrum) gave a performance increase of 0.57%, compared to performance of the single best RGB band (red). Additionally, red bands had the highest coefficients/preference in our classifiers. Principal components analysis of the multispectral imagery indicates only two significant image bands, which is not surprising given the presence of two stains.</p> <p>Conclusion</p> <p>Our results indicate that multispectral imagery for routine H&E stained histopathology provides minimal additional spectral information for a pixel-level nuclear classification task than would standard RGB imagery.</p

Epigenetic Alterations Are Critical for Fear Memory Consolidation and Synaptic Plasticity in the Lateral Amygdala

Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Spatial and Spectral Coherent Control with Frequency Combs

Quantum coherent control (1-3) is a powerful tool for steering the outcome of quantum processes towards a desired final state, by accurate manipulation of quantum interference between multiple pathways. Although coherent control techniques have found applications in many fields of science (4-9), the possibilities for spatial and high-resolution frequency control have remained limited. Here, we show that the use of counter-propagating broadband pulses enables the generation of fully controlled spatial excitation patterns. This spatial control approach also provides decoherence reduction, which allows the use of the high frequency resolution of an optical frequency comb (10,11). We exploit the counter-propagating geometry to perform spatially selective excitation of individual species in a multi-component gas mixture, as well as frequency determination of hyperfine constants of atomic rubidium with unprecedented accuracy. The combination of spectral and spatial coherent control adds a new dimension to coherent control with applications in e.g nonlinear spectroscopy, microscopy and high-precision frequency metrology.Comment: 12 page

Dynamic pigmentary and structural coloration within cephalopod chromatophore organs

Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

A qualitative synthesis of the positive and negative impacts related to delivery of peer-based health interventions in prison settings

Background Peer interventions involving prisoners in delivering peer education and peer support in a prison setting can address health need and add capacity for health services operating in this setting. This paper reports on a qualitative synthesis conducted as part of a systematic review of prison-based peer interventions. One of the review questions aimed to investigate the positive and negative impacts of delivering peer interventions within prison settings. This covered organisational and process issues relating to peer interventions, including prisoner and staff views. Methods A qualitative synthesis of qualitative and mixed method studies was undertaken. The overall study design comprised a systematic review involving searching, study selection, data extraction and validity assessment. Studies reporting interventions with prisoners or ex-prisoners delivering education or support to prisoners resident in any type of prison or young offender institution, all ages, male and female, were included. A thematic synthesis was undertaken with a subset of studies reporting qualitative data (n=33). This involved free coding of text reporting qualitative findings to develop a set of codes, which were then grouped into thematic categories and mapped back to the review question. Results Themes on process issues and wider impacts were grouped into four thematic categories: peer recruitment training and support; organisational support; prisoner relationships; prison life. There was consistent qualitative evidence on the need for organisational support within the prison to ensure smooth implementation and on managing security risks when prisoners were involved in service delivery. A suite of factors affecting the delivery of peer interventions and the wider organisation of prison life were identified. Alongside reported benefits of peer delivery, some reasons for non-utilisation of services by other prisoners were found. There was weak qualitative evidence on wider impacts on the prison system, including better communication between staff and prisoners. Gaps in evidence were identified. Conclusions The quality of included studies limited the strength of the conclusions. The main conclusion is that peer interventions cannot be seen as independent of prison life and health services need to work in partnership with prison services to deliver peer interventions. More research is needed on long-term impacts

The Immunophilin-Like Protein XAP2 Is a Negative Regulator of Estrogen Signaling through Interaction with Estrogen Receptor α

XAP2 (also known as aryl hydrocarbon receptor interacting protein, AIP) is originally identified as a negative regulator of the hepatitis B virus X-associated protein. Recent studies have expanded the range of XAP2 client proteins to include the nuclear receptor family of transcription factors. In this study, we show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. Interestingly, we show that XAP2 downregulates the E2-dependent transcriptional activation in an estrogen receptor (ER) isoform-specific manner: XAP2 inhibits ERα but not ERβ-mediated transcription. Thus, knockdown of intracellular XAP2 levels leads to increased ERα activity. XAP2 proteins, carrying mutations in their primary structures, loose the ability of interacting with ERα and can no longer regulate ER target gene transcription. Taken together, this study shows that XAP2 exerts a negative effect on ERα transcriptional activity and may thus prevent ERα-dependent events

Communication practices in the US and Syria

This study highlights Syrian communication practices using comparative tests with the United States communication as a baseline. Additionally, theoretical findings on individualism and collectivism theory are extended to include findings from Syria. Multivariate Analysis of Covariance was used to test culture’s effect in demographically similar (in age, SES, and education) student convenience samples, with the covariate communication adaptability, on dependent variables: empathy, social confirmation, social composure, friendships, non-verbal immediacy, social self-efficacy, and general self-efficacy. Results indicated that Syrians possess more empathy, social confirmation, and perceived general self-efficacy in comparison to U.S. citizens who have greater social composure, friendships, non-verbal immediacy and social self-efficacy. These results indicate that Syrians have the strength of self-efficacy to succeed in intercultural relationships while U.S. Americans have the assets of warmth and sociability to enable successful interactions with Syrian

Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus

<p>Abstract</p> <p>Background</p> <p>Myocardial extravascular extracellular volume fraction (Ve) measures quantify diffuse fibrosis not readily detectable by conventional late gadolinium (Gd) enhancement (LGE). Ve measurement requires steady state equilibrium between plasma and interstitial Gd contrast. While a constant infusion produces steady state, it is unclear whether a simple bolus can do the same. Given the relatively slow clearance of Gd, we hypothesized that a bolus technique accurately measures Ve, thus facilitating integration of myocardial fibrosis quantification into cardiovascular magnetic resonance (CMR) workflow routines. Assuming equivalence between techniques, we further hypothesized that Ve measures would be reproducible across scans.</p> <p>Methods</p> <p>In 10 volunteers (ages 20-81, median 33 yr, 3 females), we compared serial Ve measures from a single short axis slice from two scans: first, during a constant infusion, and second, 12-50 min after a bolus (0.2 mmol/kg gadoteridol) on another day. Steady state during infusion was defined when serial blood and myocardial T1 data varied <5%. We measured T1 on a 1.5 T Siemens scanner using a single-shot modified Look Locker inversion recovery sequence (MOLLI) with balanced SSFP. To shorten breath hold times, T1 values were measured with a shorter sampling scheme that was validated with spin echo relaxometry (TR = 15 sec) in CuSO4-Agar phantoms. Serial infusion vs. bolus Ve measures (n = 205) from the 10 subjects were compared with generalized estimating equations (GEE) with exchangeable correlation matrices. LGE images were also acquired 12-30 minutes after the bolus.</p> <p>Results</p> <p>No subject exhibited LGE near the short axis slices where Ve was measured. The Ve range was 19.3-29.2% and 18.4-29.1% by constant infusion and bolus, respectively. In GEE models, serial Ve measures by constant infusion and bolus did not differ significantly (difference = 0.1%, p = 0.38). For both techniques, Ve was strongly related to age (p < 0.01 for both) in GEE models, even after adjusting for heart rate. Both techniques identically sorted older individuals with higher mean Ve values.</p> <p>Conclusion</p> <p>Myocardial Ve can be measured reliably and accurately 12-50 minutes after a simple bolus. Ve measures are also reproducible across CMR scans. Ve estimation can be integrated into CMR workflow easily, which may simplify research applications involving the quantification of myocardial fibrosis.</p