Bioactivating a bone substitute accelerates graft incorporation in a murine model of vertical ridge augmentation

OBJECTIVE: Compared to autologous bone grafts, allogeneic bone grafts integrate slowly, which can adversely affect clinical outcomes. Here, our goal was to understand the molecular mechanisms underlying graft incorporation, and then test clinically feasible methods to accelerate this process. METHODS: Wild-type and transgenic Wnt reporter mice were used in a vertical ridge augmentation procedure. The surgery consisted of tunneling procedure to elevate the maxillary edentulous ridge periosteum, followed by the insertion of bone graft. Micro-computed tomographic imaging, and molecular/cellular analyses were used to follow the bone graft over time. Sclerostin null mice, and mice carrying an activated form of β-catenin were evaluated to understand how elevated Wnt signaling impacted edentulous ridge height and based on these data, a biomimetic strategy was employed to combine bone graft particles with a formulation of recombinant WNT protein. Thereafter, the rate of graft incorporation was evaluated. RESULTS: Tunneling activated osteoprogenitor cell proliferation from the periosteum. If graft particles were present, then osteoprogenitor cells attached to the matrix and gave rise to new bone that augmented edentulous ridge height. Graft particles alone did not stimulate osteoprogenitor cell proliferation. Based on the thicker edentulous ridges in mice with amplified Wnt signaling, a strategy was undertaken to load bone graft particles with WNT; this combination was sufficient to accelerate the initial step of graft incorporation. SIGNIFICANCE: Local delivery of a WNT protein therapeutic has the potential to accelerate graft incorporation, and thus shorten the time to when the graft can support a dental implant

Normally-off GaN transistors for power applications

Normally-off high voltage GaN-HFETs for switching applications are presented. Normally-off operation with threshold voltages of 1 V and more and with 5 V gate swing has been obtained by using p-type GaN as gate. Different GaN-based buffer types using doping and backside potential barriers have been used to obtain blocking strengths up to 1000 V. The increase of the dynamic on-state resistance is analyzed for the different buffer types. The best trade-off between low dispersion and high blocking strength was obtained for a modified carbon-doped GaN-buffer that showed a 2.6x increase of the dynamic on-state resistance for 500 V switching as compared to switching from 20 V off-state drain bias. Device operation up to 200 °C ambient temperature without any threshold voltage shift is demonstrated

Phase structure and phase transitions of the SU(2) x O(N) symmetric scalar field theory

Radiatively induced SU(2) symmetry breaking is shown to be a genuine feature of SU(2) x O(N) globally symmetric renormalisable field theories in the large N limit, describing interaction of a complex SU(2) doublet, O(N)-singlet field with an SU(2) singlet, O(N) vector. Symmetry breaking solutions are found even when all fields have positive renormalised squared mass. The emerging novel mechanism of symmetry breaking can reproduce with a choice of N~300 the standard range of the electroweak condensate and the Higgs mass occurring in the extended Higgs dynamics of an SU(2) symmetric Gauge+Higgs model.Comment: 6 pages, 3 figures; the role of the cut-off in the effective theory is discussed, references added; to appear in Europhys. Let

A randomised controlled trial comparing graded exercise treatment and usual physiotherapy for patients with non-specific neck pain (the GET UP neck pain trial).

Evidence supports exercise-based interventions for the management of neck pain, however there is little evidence of its superiority over usual physiotherapy. This study investigated the effectiveness of a group neck and upper limb exercise programme (GET) compared with usual physiotherapy (UP) for patients with non-specific neck pain. A total of 151 adult patients were randomised to either GET or UP. The primary measure was the Northwick Park Neck pain Questionnaire (NPQ) score at six weeks, six months and 12 months. Mixed modelling identified no difference in neck pain and function between patients receiving GET and those receiving UP at any follow-up time point. Both interventions resulted in modest significant and clinically important improvements on the NPQ score with a change score of around 9% between baseline and 12 months. Both GET and UP are appropriate clinical interventions for patients with non-specific neck pain, however preferences for treatment and targeted strategies to address barriers to adherence may need to be considered in order to maximise the effectiveness of these approaches

Strong electroweak phase transitions without collider traces

We discuss the question if the upcoming generation of collider and low-energy experiments can successfully probe the nature of the electroweak phase transition. In particular, we are interested in phase transitions strong enough for electroweak baryogenesis or even for a production of gravitational radiation observable by the Big Bang Observer. As an explicit example, we present an analysis in a singlet extension of the Standard Model. We focus on the region in parameter space where the model develops no significant deviation in its low energy phenomenology from the Standard Model. Nevertheless, this class of models can develop a very strong phase transition.Comment: 20 pages, 6 figures, some comments and references adde

Sudden drop of fractal dimension of electromagnetic emissions recorded prior to significant earthquake

The variation of fractal dimension and entropy during a damage evolution process, especially approaching critical failure, has been recently investigated. A sudden drop of fractal dimension has been proposed as a quantitative indicator of damage localization or a likely precursor of an impending catastrophic failure. In this contribution, electromagnetic emissions recorded prior to significant earthquake are analysed to investigate whether they also present such sudden fractal dimension and entropy drops as the main catastrophic event is approaching. The pre-earthquake electromagnetic time series analysis results reveal a good agreement to the theoretically expected ones indicating that the critical fracture is approaching

Leptogenesis from Soft Supersymmetry Breaking (Soft Leptogenesis)

Soft leptogenesis is a scenario in which the cosmic baryon asymmetry is produced from a lepton asymmetry generated in the decays of heavy sneutrinos (the partners of the singlet neutrinos of the seesaw) and where the relevant sources of CP violation are the complex phases of soft supersymmetry-breaking terms. We explain the motivations for soft leptogenesis, and review its basic ingredients: the different CP-violating contributions, the crucial role played by thermal corrections, and the enhancement of the efficiency from lepton flavour effects. We also discuss the high temperature regime $T > 10^7$ GeV in which the cosmic baryon asymmetry originates from an initial asymmetry of an anomalous $R$-charge, and soft leptogenesis reembodies in $R$-genesis.Comment: References updated. Some minor corrections to match the published versio

Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

Dirac Neutrinos, Dark Energy and Baryon Asymmetry

We explore a new origin of neutrino dark energy and baryon asymmetry in the universe. The neutrinos acquire small masses through the Dirac seesaw mechanism. The pseudo-Nambu-Goldstone boson associated with neutrino mass-generation provides a candidate for dark energy. The puzzle of cosmological baryon asymmetry is resolved via neutrinogenesis.Comment: 6 pages, 1 figure. Accepted by JCAP (only minor rewordings, refs added

Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

Background: Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. Objectives: This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Method: Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. Results: QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement between palpation and QF in identifying hypo-mobile segments (Kappa 0.04-0.06). Conclusions: This study found no differences in cervical sagittal IV-RoM between patients with non-specific neck pain and matched controls. There was a modest dose-response relationship between the number of manipulations given and number of levels increasing IV-RoM - providing evidence that neck manipulation has a mechanical effect at segmental levels. However, patient-reported outcomes were not related to this