The use of a synthetic shoulder patch for large and massive rotator cuff tears – a feasibility study

Background The aim of this study was to explore the feasibility of using a non-absorbable biocompatible polyester patch to augment open repair of massive rotator cuff tears (Patch group) and compare outcomes with other treatment options (Non-patch group). Methods Participants referred to orthopaedic clinics for rotator cuff surgery were recruited. Choice of intervention (Patch or Non-patch) was based on patient preference and intra-operative findings. Oxford Shoulder Score (OSS), Shoulder Pain and Disability Index (SPADI), and Constant score were completed at baseline and 6 months. Shoulder MRI was performed at baseline and 6 months to assess fat fraction and Goutallier classification pre- and post- treatment. Feasibility outcomes (including retention, consent and missing data) were assessed. Results Sixty-eight participants (29 in the Patch group, 39 in Non-patch group) were included (mean age 65.3 years). Conversion to consent (92.6%), missing data (0% at baseline), and attrition rate (16%) were deemed successful feasibility endpoints. There was significant improvement in the Patch group compared to Non-patch at 6 months in OSS (difference in medians 9.76 (95% CI 2.25, 17.29) and SPADI: 22.97 (95% CI 3.02, 42.92), with no substantive differences in Constant score. The patch group had a higher proportion of participants improving greater than MCID for OSS (78% vs 62%) and SPADI (63% vs 50%) respectively. Analysis of the 48 paired MRIs demonstrated a slight increase in the fat fraction for supraspinatus (53 to 55%), and infraspinatus (26 to 29%) at 6 months. These differences were similar and in the same direction when the participants were analysed by treatment group. The Goutallier score remained the same or worsened one grade in both groups equally. Conclusions This study indicates that a definitive clinical trial investigating the use of a non-absorbable patch to augment repair of massive rotator cuff tears is feasible. In such patients, the patch has the potential to improve shoulder symptoms at 6 months

A user-centred design framework for disaster risk visualisation

Visualisations are powerful communication tools that have the potential to help societies assess and manage natural hazard and disaster risks. However, the diversity of risk management contexts and user characteristics is a challenge to develop understandable and useable visualisations. We conducted a systematic literature review to understand the current state developing disaster risk visualisations following design best practices and accounting for the heterogeneity between end-users and disaster risk contexts. We find that, despite being widely recommended, tailoring visualisations to users through the process of user-centred design remains a relatively unexplored topic within disaster risk. To address this, we present a unifying user-centred design framework for disaster risk visualisation, based on existing visualisation frameworks. The framework contains three phases: the Define phase, which aims to define and characterise the disaster risk management context and end-user group who will benefit from a visualisation; the Design phase, which is highly iterative and presents an opportunity to test how users interpret different design elements; and the Refine phase, which focuses on evaluating how users understand, respond to, and make decisions based on the visualisation. The framework is sufficiently flexible to be applied to any disaster risk management and natural hazard context to identify challenges and design effective disaster risk visualisations that are understandable and useable

The influence of rs53576 polymorphism in the oxytocin receptor (OXTR) gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis

Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically cognitive empathy (CE) and affective empathy (AE), in healthy adults. Twenty cohorts of 8933 participants aged 18-98 were identified, including data from the Sydney Memory and Ageing Study, a cohort of older community adults. Meta-analyses found G homozygotes had greater generalized empathic abilities only in young to middle-aged adults. While meta-analyses of empathy subdomains yielded no significant overall effects, there were differential effects based on ethnicity. G homozygotes were associated with greater CE abilities in Asian cohorts (standardized mean difference; SMD: 0.09 [2.8·10-3-0.18]), and greater AE performance in European cohorts [SMD: 0.12 (0.04-0.21)]. The current literature highlights a need for further work that distinguishes between genetic and ethnocultural effects and explores effects of advanced age on this relationship

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

Objectives To assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist’s scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times. Methods In this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson’s correlation between visit 1 measurements and return to play times was assessed. Results There were significant differences between visits in BAMIC scores (Z = − 2.088; p = 0.037), modified Peetrons (Z = − 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not. Conclusions T2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring. Key Points • Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI. • Measurements of T2 and diffusion using MRI are not as good as a radiologist’s visual report at predicting return to play time after acute muscle tear

Co-directional replication-transcription conflicts lead to replication restart

August 24, 2011Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability1, 2. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication3. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10–20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign2, 4, 5, 6, 7, 8, 9. Biochemical analyses indicate that head-on encounters10 are more deleterious than co-directional encounters8 and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.Biotechnology and Biological Sciences Research Council (Great Britain) (Grant BB/E006450/1)Wellcome Trust (London, England) (Grant 091968/Z/10/Z)National Institutes of Health (U.S.) (Grant GM41934)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM093408)Biotechnology and Biological Sciences Research Council (Great Britain) (Sabbatical Visit

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Anterior interosseous nerve syndrome: retrospective analysis of 14 patients

Introduction: The anterior interosseous nerve (AIN) is a only motor nerve innervating the deep muscles of the forearm. Its compression is rare. We present a retrospective analysis of 14 patients with an AIN syndrome with a variety of clinical manifestations who underwent operative and conservative treatment. Patients and methods: Fourteen patients (six female, eight male, mean age 48 ± 9 years) were included. In six patients, the right limb was affected, and in eight patients the left limb. Conservative treatment was started for every patient. If no signs of recovery appeared within 3 months, operative exploration was performed. Final assessment was performed between 2 and 9 years after the onset of paralysis (mean duration of follow-up 46 ± 11 months). Patients were examined clinically for return of power, range of motion, pinch and grip strengths. Also the disability of the arm, shoulder, and hand (DASH) score was calculated. Results: Seven of our 14 patients had incomplete AIN palsy with isolated total loss of function of flexor pollicis longus (FPL), five of FPL and flexor digitorum profundus (FDP)1 simultaneously, and two of FDP1. Weakness of FDP2 could be seen in four patients. Pronator teres was paralysed in two patients. Pain in the forearm was present in nine patients. Four patients had predisposing factors. Eight patients treated conservatively exhibited spontaneous recovery from their paralysis during 3-12 months after the onset. In six patients, the AIN was explored 12 weeks after the initial symptoms and released from compressing structures. Thirteen patients showed good limb function. In one patient with poor result a tendon transfer was necessary. The DASH score of patients treated conservatively and operatively presented no significant difference. Conclusion: AIN syndrome can have different clinical manifestations. If no signs of spontaneous recovery appear within 12 weeks, operative treatment should be performed

Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies