Modulation of somatosensory processing by action.

Psychophysical evidence suggests that sensations arising from our own movements are diminished when predicted by motor forward models and that these models may also encode the timing and intensity of movement. Here we report a functional magnetic resonance imaging study in which the effects on sensation of varying the occurrence, timing and force of movements were measured. We observed that tactile-related activity in a region of secondary somatosensory cortex is reduced when sensation is associated with movement and further that this reduction is maximal when movement and sensation occur synchronously. Motor force is not represented in the degree of attenuation but rather in the magnitude of this region's response. These findings provide neurophysiological correlates of previously-observed behavioural forward-model phenomena, and advocate the adopted approach for the study of clinical conditions in which forward-model deficits have been posited to play a crucial role

Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain

Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. Methodology/Principal Findings: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. Conclusions/Significance: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available

Acupressure for smoking cessation – a pilot study

BACKGROUND: Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study. METHODS: An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO ≤ 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale. RESULTS: From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week. CONCLUSION: Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested

Spectral plots and the representation and interpretation of biological data

It is basic question in biology and other fields to identify the char- acteristic properties that on one hand are shared by structures from a particular realm, like gene regulation, protein-protein interaction or neu- ral networks or foodwebs, and that on the other hand distinguish them from other structures. We introduce and apply a general method, based on the spectrum of the normalized graph Laplacian, that yields repre- sentations, the spectral plots, that allow us to find and visualize such properties systematically. We present such visualizations for a wide range of biological networks and compare them with those for networks derived from theoretical schemes. The differences that we find are quite striking and suggest that the search for universal properties of biological networks should be complemented by an understanding of more specific features of biological organization principles at different scales.Comment: 15 pages, 7 figure

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas. METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed. RESULTS: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis. CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR

Validation of the AASLD recommendations for Classification of Oesophageal Varices in Clinical Practice

Background & Aims The American Association for the Study of Liver Diseases recommends the use of a 2‐grade classification system (small and large) to describe the size of oesophageal varices (OV). Data on observer agreement (OA) on this system are currently lacking. We aimed to evaluate this classification and compare it to the widely used 3‐grade classification (grade 1 ‘small’, grade 2 ‘medium’, grade 3 ‘large’) among operators of variable experience. Methods High‐definition video recordings of 100 patients with cirrhosis were prospectively collected using standardised criteria. Nine observers of variable experience performed independent evaluations of the videos in random order. OV were scored using both systems. All assessments were repeated a year later by the same observers to assess intra‐observer agreement. Results Interobserver agreement (all observers) using the 2‐grade and the 3‐grade system was k = 0.71 (95% CI: 0.64‐0.78) and k = 0.73 (95% CI: 0.66‐0.79) respectively. When using the 2‐grade system, intra‐observer agreement between hepatologists (n = 3), luminal gastroenterologists (n = 3) and trainee gastroenterologists (n = 3) was k = 0.89 (95% CI: 0.86‐0.91), k = 0.72 (95% CI: 0.67‐0.77), and k = 0.74 (95% CI: 0.67‐0.8) respectively. With the 3‐grade system; intra‐observer agreement between the same three subgroups were k = 0.9 (95% CI: 0.87‐0.92), k = 0.73 (95% CI: 0.68‐0.78), k = 0.77 (95% CI: 0.71‐0.82) respectively. Conclusions There was no difference in OA between the 2‐grade and 3‐grade classification systems. Hepatologists had significantly higher levels of consistency in grading OV. This may have implications to create alternative training models for residents and fellows in the recognition and grading of OV

Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans

Statistical inference of the fundamental parameters of supersymmetric theories is a challenging and active endeavor. Several sophisticated algorithms have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and nested sampling techniques are geared towards Bayesian inference, they have also been used to estimate frequentist confidence intervals based on the profile likelihood ratio. We investigate the performance and appropriate configuration of MultiNest, a nested sampling based algorithm, when used for profile likelihood-based analyses both on toy models and on the parameter space of the Constrained MSSM. We find that while the standard configuration is appropriate for an accurate reconstruction of the Bayesian posterior, the profile likelihood is poorly approximated. We identify a more appropriate MultiNest configuration for profile likelihood analyses, which gives an excellent exploration of the profile likelihood (albeit at a larger computational cost), including the identification of the global maximum likelihood value. We conclude that with the appropriate configuration MultiNest is a suitable tool for profile likelihood studies, indicating previous claims to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report. Matches version accepted by JHE

Central Asia and the globalisation of the contemporary legal consciousness

What is the logic which governs the processes of legal globalization? How does the transnational proliferation of legal forms operate in the contemporary geo-juridical space? What are the main defining characteristics of the currently dominant mode of transnational legal consciousness and how can the concept of legal consciousness help us understand better the historical ebb and flow of the Western-led projects of good governance promotion in regions like Central Asia after the fall of the Soviet Union? Using Duncan Kennedy’s seminal essay Three Globalizations of Law and Legal Thought as its starting platform, this essay seeks to explore these and a series of other related questions, while also drawing on the work of the Greek Marxist lawyer-philosopher Nicos Poulantzas to help elucidate some latent analytical stress-points in Kennedy’s broader theoretical framework. Reacting against the neo-Orientalist tone adopted across much of the contemporary field of Central Asian studies, it develops an alternative account of the internal history of the legal-globalizational encounter between the Western-based reform entrepreneurs and the national legal-political elites in Central Asia in the post-1991 period, complementing it with a detailed description of the general institutional and discursive structures within which this encounter took place

Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

Perioperative celecoxib administration for pain management after total knee arthroplasty – A randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.</p> <p>Methods</p> <p>This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.</p> <p>Results</p> <p>Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 ± 1.68 vs. 3.43 ± 1.50, p = 0.03) and 72 hrs (1.78 ± 1.66 vs. 3.17 ± 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8° ± 17.3° vs. 25.8° ± 11.5°, p = 0.01 (day 1); 60.7° ± 18.1° vs. 45.0° ± 17.3°, p = 0.004 (day 2); 77.7° ± 15.1° vs. 64.3° ± 16.9°, p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.</p> <p>Conclusion</p> <p>Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00598234</p