Muon spin spectroscopy: magnetism, soft matter and the bridge between the two

LS would like to acknowledge financial support from the Swiss National Science Foundation, grant numbers PBFRP2-138632 and PBFRP2-142820. AD would like to acknowledge financial support from the UK Engineering and Physical Sciences Research Council, grant number EP/G054568/1, the European Union Seventh Framework Programme project NMP3-SL- 2011-263104 ‘HINTS’ and the European Research Council project ‘Muon Spin Spectroscopy of Excited States (MuSES)’ proposal number 307593LS would like to acknowledge financial support from the Swiss National Science Foundation, grant numbers PBFRP2-138632 and PBFRP2-142820. AD would like to acknowledge financial support from the UK Engineering and Physical Sciences Research Council, grant number EP/G054568/1, the European Union Seventh Framework Programme project NMP3-SL- 2011-263104 ‘HINTS’ and the European Research Council project ‘Muon Spin Spectroscopy of Excited States (MuSES)’ proposal number 307593LS would like to acknowledge financial support from the Swiss National Science Foundation, grant numbers PBFRP2-138632 and PBFRP2-142820. AD would like to acknowledge financial support from the UK Engineering and Physical Sciences Research Council, grant number EP/G054568/1, the European Union Seventh Framework Programme project NMP3-SL- 2011-263104 ‘HINTS’ and the European Research Council project ‘Muon Spin Spectroscopy of Excited States (MuSES)’ proposal number 30759

Effects of Rivaroxaban on Biomarkers of Coagulation and Inflammation: A Post Hoc Analysis of the X-VeRT Trial.

Introduction  This X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin-antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Methods  Samples for biomarker analysis were taken at baseline ( n  = 958) and treatment completion (42 days after cardioversion; n  = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Results  Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (-32.3 and -37.6%, respectively), TAT (-28.0 and -23.1%, respectively), hs-CRP (-12.5 and -17.9%, respectively), and hs-IL-6 (-9.2 and -9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (-53.0%) but not in those receiving rivaroxaban (2.7%). Conclusion  Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited

Seasonality of biological and physical controls on surface ocean CO2 from hourly observations at the Southern Ocean Time Series site south of Australia

The Subantarctic Zone (SAZ), which covers the northern half of the Southern Ocean between the Subtropical and Subantarctic Fronts, is important for air-sea CO2 exchange, ventilation of the lower thermocline, and nutrient supply for global ocean productivity. Here we present the first high-resolution autonomous observations of mixed layer CO2 partial pressure (pCO(2)) and hydrographic properties covering a full annual cycle in the SAZ. The amplitude of the seasonal cycle in pCO(2) (similar to 60 mu atm), from near-atmospheric equilibrium in late winter to similar to 330 mu atm in midsummer, results from opposing physical and biological drivers. Decomposing these contributions demonstrates that the biological control on pCO(2) (up to 100 mu atm), is 4 times larger than the thermal component and driven by annual net community production of 2.45 +/- 1.47 mol C m(-2) yr(-1). After the summer biological pCO(2) depletion, the return to near-atmospheric equilibrium proceeds slowly, driven in part by autumn entrainment into a deepening mixed layer and achieving full equilibration in late winter and early spring as respiration and advection complete the annual cycle. The shutdown of winter convection and associated mixed layer shoaling proceeds intermittently, appearing to frustrate the initiation of production. Horizontal processes, identified from salinity anomalies, are associated with biological pCO(2) signatures but with differing impacts in winter (when they reflect far-field variations in dissolved inorganic carbon and/or biomass) and summer (when they suggest promotion of local production by the relief of silicic acid or iron limitation). These results provide clarity on SAZ seasonal carbon cycling and demonstrate that the magnitude of the seasonal pCO(2) cycle is twice as large as that in the subarctic high-nutrient, low-chlorophyll waters, which can inform the selection of optimal global models in this region

Methodological bias in cluster randomised trials

Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Follow-up investigations of tau protein and S-100B levels in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

Background: S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment. Patients and Methods: We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B. Results: Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B. Conclusion: We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases. Copyright (C) 2005 S. Karger AG, Basel

Importance of Spin-Orbit Interaction for the Electron Spin Relaxation in Organic Semiconductors

Despite the great interest organic spintronics has recently attracted, there is only a partial understanding of the fundamental physics behind electron spin relaxation in organic semiconductors. Mechanisms based on hyperfine interaction have been demonstrated, but the role of the spin-orbit interaction remains elusive. Here, we report muon spin spectroscopy and time-resolved photoluminescence measurements on two series of molecular semiconductors in which the strength of the spin-orbit interaction has been systematically modified with a targeted chemical substitution of different atoms at a particular molecular site. We find that the spin-orbit interaction is a significant source of electron spin relaxation in these materials

Advanced Multilevel Node Separator Algorithms

A node separator of a graph is a subset S of the nodes such that removing S and its incident edges divides the graph into two disconnected components of about equal size. In this work, we introduce novel algorithms to find small node separators in large graphs. With focus on solution quality, we introduce novel flow-based local search algorithms which are integrated in a multilevel framework. In addition, we transfer techniques successfully used in the graph partitioning field. This includes the usage of edge ratings tailored to our problem to guide the graph coarsening algorithm as well as highly localized local search and iterated multilevel cycles to improve solution quality even further. Experiments indicate that flow-based local search algorithms on its own in a multilevel framework are already highly competitive in terms of separator quality. Adding additional local search algorithms further improves solution quality. Our strongest configuration almost always outperforms competing systems while on average computing 10% and 62% smaller separators than Metis and Scotch, respectively

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.

Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becomes deposited in collagenous tissues and subsequently undergoes polymerisation, principally in the cartilages of loaded joints, in a process known as ochronosis. This results in an early-onset, devastating osteoarthropathy for which there is currently no effective treatment. We recently described the natural history of ochronosis in a murine model of AKU, demonstrating that deposition of ochronotic pigment begins very early in life and accumulates with age. Using this model, we were able to show that lifetime treatment with nitisinone, a potential therapy for AKU, was able to completely prevent deposition of ochronotic pigment. However, although nitisinone has been shown to inhibit ochronotic deposition, whether it can also facilitate removal of existing pigment has not yet been examined. We describe here that midlife administration of nitisinone to AKU mice arrests further deposition of ochronotic pigment in the tibiofemoral joint, but does not result in the clearance of existing pigment. We also demonstrate the dose-dependent response of plasma HGA to nitisinone, highlighting its efficacy for personalised medicine, where dosage can be tailored to the individual AKU patient