Nodular lymphocyte predominant Hodgkin lymphoma behaves as a distinct clinical entity with good outcome: evidence from 14-year followup in the West of Scotland Cancer Network

Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-center derived B-cell non-Hodgkin lymphoma (NHL) than with classical Hodgkin lymphoma (cHL). Management of NLPHL remains controversial. In a 14-year multicenter series, 69 cases were analyzed, and the median follow-up was 53 months (range 11–165.) B-symptoms were present in only 4.3% of patients, and 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6%), chemotherapy (21.7%), combined modality (17.4%), and observation (7.2%). In all, 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5-year relapse-free survival was 92%, transformation-free survival 98.4%, and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at an early stage without risk factors. It has an excellent outcome. It may be possible, in early-stage disease, to reduce the intensity of therapy in NLPHL, to single-modality radiotherapy, without affecting OS

Violation of a Bell inequality in two-dimensional spin-orbit hypoentangled subspaces

Based on spin-orbit coupling induced by q-plates, we present a feasible experimental proposal for preparing two-dimensional spatially inhomogeneous polarizations of light. We further investigate the quantum correlations between these inhomogeneous polarizations of photon pairs generated by spontaneous parametric down-conversion, which in essence describe the so-called hypoentanglement that is established between composite spin-orbit variables of photons. The violation of the Clauser-Horne-Shimony-Holt-Bell inequality is predicted with S=2\sqrt2 to illustrate the entangled nature of the cylindrical symmetry of spatially inhomogeneous polarizations.Comment: 14pages,3 figures, submitte

Development of a facial expression scale using footrot and mastitis as models of pain in sheep

Management of pain in sheep is limited by the challenges of recognising and accurately quantifying pain in this species. The use of facial expression scoring to assess pain is a well-utilised, practical tool in both humans and non-human animals. The objective of this study was to develop a standardised facial expression pain scale for adult sheep, that could be used reliably and accurately to detect pain associated with naturally occurring painful diseases, such as footrot and mastitis. We also investigated whether the scale could be reliably and accurately utilised by observers after training, enabling the development of an on-farm pain assessment tool. The Sheep Pain Facial Expression Scale (SPFES) was able to correctly identify sheep suffering from disease with a high degree of accuracy (AUC; Footrot: 0.81, Mastitis: 0.80). Diseased sheep scored higher on the scale than controls on the day of disease identification (P<0.05) and diseased sheep showed changes in their facial expression after treatment (P<0.001). The abnormal facial expressions of diseased sheep reduced over time, and at recovery were in line with control sheep. Control sheep did not change their facial expression over time. Five scorers who were trained to use the developed scale also assessed the facial expressions of sheep. The scorers were blind to treatment and session. Scorers reliably (ICC: 0.86) and accurately (α = 0.86) identified changes in the facial expression of sheep with footrot over time (P<0.05), and scored control sheep consistently low over time. The SPFES offers a reliable and effective method of assessing pain in sheep after minimal training.We would like to thank the EU VII Framework Program (FP7-KBBE-2010-4) for funding this study as part of the AWIN project. Boehringer Imgelheim Ltd are thanked for providing the meloxicam used in this study.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.applanim.2016.01.00

A longitudinal test of the predictions of the interpersonal-psychological theory of suicidal behaviour for passive and active suicidal ideation in a large community-based cohort

BACKGROUND The Interpersonal-Psychological Theory of Suicide (IPTS) aims to elucidate the key antecedents of suicide deaths. Limited research has tested the IPTS in a community setting, and very little longitudinal research has been conducted. The current study longitudinally tested the predictions of the IPTS for suicidal ideation in a large population-based sample. METHODS The PATH through Life study assesses three age cohorts (20's, 40's, 60's) every four years. Two interpersonal factors were estimated at the third wave of assessment: thwarted belongingness (TB) and perceived burdensomeness (PB). The roles of these factors in suicide ideation (active and passive) four years later were estimated using logistic regression models (n = 4545). RESULTS A one SD increase in TB was associated with increased odds of 37% for passive ideation and 24% for active ideation. For PB, odds were increased 2.5-fold for passive ideation and 2.4-fold for active ideation. A significant negative PB × TB interaction was found for passive but not active ideation. Effects were not consistent by age group or gender. LIMITATIONS Proxy measures were used to assess the constructs. The extended timeframe and low prevalence of suicidal ideation limited power to find effects within subgroups. CONCLUSIONS Although TB and PB were individually associated with suicidal thoughts, little evidence was found for the key predictions of the IPTS longitudinally. Further investigation of the dynamic interplay between interpersonal factors over time is needed.The study was supported by National Health and Medical Research Council (NHMRC) grants 973302, 179805, 350833, 157125 and Australian Research Council grant 130101705. PJB, ALC and HC are supported by NHMRC Fellowships 1083311, 1122544 and 1056964

Magnetic Resonance Imaging-Based Assessment of Breast Cancer-Related Lymphoedema Tissue Composition.

OBJECTIVES: The aim of this study was to propose a magnetic resonance imaging acquisition and analysis protocol that uses image segmentation to measure and depict fluid, fat, and muscle volumes in breast cancer-related lymphoedema (BCRL). This study also aims to compare affected and control (unaffected) arms of patients with diagnosed BCRL, providing an analysis of both the volume and the distribution of the different tissue components. MATERIALS AND METHODS: The entire arm was imaged with a fluid-sensitive STIR and a 2-point 3-dimensional T1W gradient-echo-based Dixon sequences, acquired in sagittal orientation and covering the same imaging volume. An automated image postprocessing procedure was developed to simultaneously (1) contour the external volume of the arm and the muscle fascia, allowing separation of the epifacial and subfascial volumes; and to (2) separate the voxels belonging to the muscle, fat, and fluid components. The total, subfascial, epifascial, muscle (subfascial), fluid (epifascial), and fat (epifascial) volumes were measured in 13 patients with unilateral BCRL. Affected versus unaffected volumes were compared using a 2-tailed paired t test; a value of P < 0.05 was considered to be significant. Pearson correlation was used to investigate the linear relationship between fat and fluid excess volumes. The distribution of fluid, fat, and epifascial excess volumes (affected minus unaffected) along the arm was also evaluated using dedicated tissue composition maps. RESULTS: Total arm, epifascial, epifascial fluid, and epifascial fat volumes were significantly different (P < 0.0005), with greater volume in the affected arms. The increase in epifascial volume (globally, 94% of the excess volume) constituted the bulk of the lymphoedematous swelling, with fat comprising the main component. The total fat excess volume summed over all patients was 2.1 times that of fluid. Furthermore, fat and fluid excess volumes were linearly correlated (Pearson r = 0.75), with the fat excess volume being greater than the fluid in 11 subjects. Differences in muscle compartment volume between affected and unaffected arms were not statistically significant, and contributed only 6% to the total excess volume. Considering the distribution of the different tissue excess volumes, fluid accumulated prevalently around the elbow, with substantial involvement of the upper arm in only 3 cases. Fat excess volume was generally greater in the upper arm; however, the relative increase in epifascial volume, which considers the total swelling relative to the original size of the arm, was in 9 cases maximal within the forearm. CONCLUSIONS: Our measurements indicate that excess of fat within the epifascial layer was the main contributor to the swelling, even when a substantial accumulation of fluid was present. The proposed approach could be used to monitor how the internal components of BCRL evolve after presentation, to stratify patients for treatment, and to objectively assess treatment response. This methodology provides quantitative metrics not currently available during the standard clinical assessment of BCRL and shows potential for implementation in clinical practice

A 2-D π–π dimer model system to investigate structure-charge transfer relationships in rubrene

© The Royal Society of Chemistry 2019Rubrene (5,6,11,12-tetraphenyltetracene) is undoubtedly one of the best performing organic charge transfer mediating materials, with experimentally determined mobilities up to 40 cm2 V−1 s−1. Consequently, there has been increasing interest by means of crystal engineering in trying to generate rubrene-based materials with analogous or even superior conducting properties. Often, experimental measurements are carried out in thin film architectures of these materials, where measured properties can be detrimentally impacted by device manufacture rather than intrinsic charge transfer properties of the material. The latter results in discarding potential good performers. To address these concerns, we report a two-dimensional model system that will allow researchers to predict charge transfer properties of their materials solely requiring the coordinates of the π–π stacking motifs. We envisaged this study to be of significant interest to the increasingly large community of materials scientists devoted to the realisation of improved organic charge mediating materials and particularly to those engaged in exploiting rubrene-based architectures.Peer reviewedFinal Accepted Versio

Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor

Background: BQCA is a selective allosteric modulator of the M1 mAChR. Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling. Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erativity with orthosteric ligands. Significance: Understanding the structural basis of BQCA function can provide insight into the design of more tailored allosteric ligands

Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor

Background: Selective and potent positive allosteric modulators (PAMs) of the M1 mAChR have been recently described. Results: Use of structural analogues and mutagenic mapping identified the mechanistic basis for increased PAM activity. Conclusion: Combined analytical, structure-function, and modeling approaches uncover allosteric mechanisms at the M1 mAChR. Significance: New chemical space can be explored in the development of tailored M1 mAChR PAMs

A novel approach to evaluate spatial resolution of MRI clinical images for optimization and standardization of breast screening protocols.

Purpose Stringent quality assurance is required in MRI breast screening to ensure that different scanners and imaging protocols reach similar diagnostic performance. The authors propose a methodology, based on power spectrum analysis (PSA), to evaluate spatial resolution in clinical images. To demonstrate this approach, the authors have retrospectively compared two MRI sequences commonly employed in breast screening.Methods In a novel approach to PSA, spatial frequency response curves (SFRCs) were extracted from the images. The SFRC characterizes spatial resolution describing the spatial frequency content of an image over a range of frequencies. Verification of the SFRCs was performed on MRI images of Eurospin agarose gel tubes acquired with different resolution settings. SFRCs of volunteer and patient images obtained with two clinical MRI sequences were then compared. The two sequences differed primarily in k-space coverage pattern, which was either radial (RAD) or linear (LIN).Results The computed SFRCs were able to demonstrate the differences between RAD and LIN sequences in relatively small groups of subjects. The curves showed a similar pattern of decay in both volunteer and patient images, indicating that the spatial frequency response is mainly determined by the imaging protocol and not by intersubject anatomical differences. The LIN protocol produced images with increased sharpness; this was reflected in the corresponding SFRCs, which showed a higher content of spatial frequencies associated with image details.Conclusions The SFRC can provide an objective assessment of the presence of spatial details in the image and represent a useful quality assurance tool in the evaluation of different breast screening protocols. With a reference image, a comparative analysis of the SFRCs could ensure that equivalent image quality is achieved across different scanners and sites