A novel rodent neck pain model of facet-mediated behavioral hypersensitivity: implications for persistent pain and whiplash injury

Clinical, epidemiological, and biomechanical studies suggest involvement of cervical facet joint injuries in neck pain. While bony motions can cause injurious tensile facet joint loading, it remains speculative whether such injuries initiate pain. There is currently a paucity of data explicitly investigating the relationship between facet mechanics and pain physiology. A rodent model of tensile facet joint injury has been developed using a customized loading device to apply 2 separate tensile deformations (low, high; n=5 each) across the C6/C7 joint, or sham (n=6) with device attachment only. Microforceps were rigidly coupled to the vertebrae for distraction and joint motions tracked in vivo. Forepaw mechanical allodynia was measured postoperatively for 7 days as an indicator of behavioral sensitivity. Joint strains for high (33.6±3.1%) were significantly elevated (p\u3c0.005) over low (11.1±2.3%). Digitization errors (0.17±0.20%) in locating bony markers were small compared to measured strains. Allodynia was significantly elevated for high over low and sham for all postoperative days. However, allodynia for low injury was not different than sham. A greater than three-fold increase in total allodynia resulted for high compared to low, corresponding to the three-fold difference in injury strain. Findings demonstrate tensile facet joint loading produces behavioral sensitivity that varies in magnitude according to injury severity. These results suggest that a facet joint tensile strain threshold may exist above which pain symptoms result. Continued investigation into the relationship between injury mechanics and nociceptive physiology will strengthen insight into painful facet injury mechanisms

Reaction-controlled diffusion: Monte Carlo simulations

We study the coupled two-species non-equilibrium reaction-controlled diffusion model introduced by Trimper et al. [Phys. Rev. E 62, 6071 (2000)] by means of detailed Monte Carlo simulations in one and two dimensions. Particles of type A may independently hop to an adjacent lattice site provided it is occupied by at least one B particle. The B particle species undergoes diffusion-limited reactions. In an active state with nonzero, essentially homogeneous B particle saturation density, the A species displays normal diffusion. In an inactive, absorbing phase with exponentially decaying B density, the A particles become localized. In situations with algebraic decay rho_B(t) ~ t^{-alpha_B}, as occuring either at a non-equilibrium continuous phase transition separating active and absorbing states, or in a power-law inactive phase, the A particles propagate subdiffusively with mean-square displacement ~ t^{1-alpha_A}. We find that within the accuracy of our simulation data, \alpha_A = \alpha_B as predicted by a simple mean-field approach. This remains true even in the presence of strong spatio-temporal fluctuations of the B density. However, in contrast with the mean-field results, our data yield a distinctly non-Gaussian A particle displacement distribution n_A(x,t) that obeys dynamic scaling and looks remarkably similar for the different processes investigated here. Fluctuations of effective diffusion rates cause a marked enhancement of n_A(x,t) at low displacements |x|, indicating a considerable fraction of practically localized A particles, as well as at large traversed distances.Comment: Revtex, 19 pages, 27 eps figures include

Constraining mean-field models of the nuclear matter equation of state at low densities

An extension of the generalized relativistic mean-field (gRMF) model with density dependent couplings is introduced in order to describe thermodynamical properties and the composition of dense nuclear matter for astrophysical applications. Bound states of light nuclei and two-nucleon scattering correlations are considered as explicit degrees of freedom in the thermodynamical potential. They are represented by quasiparticles with medium-dependent properties. The model describes the correct low-density limit given by the virial equation of state (VEoS) and reproduces RMF results around nuclear saturation density where clusters are dissolved. A comparison between the fugacity expansions of the VEoS and the gRMF model provides consistency relations between the quasiparticles properties, the nucleon-nucleon scattering phase shifts and the meson-nucleon couplings of the gRMF model at zero density. Relativistic effects are found to be important at temperatures that are typical in astrophysical applications. Neutron matter and symmetric matter are studied in detail.Comment: 50 pages, 21 figure

Support for Aboriginal health services in reducing harms from alcohol : 2-year service provision outcomes in a cluster randomized trial

Background and aims There is a higher prevalence of unhealthy alcohol use among Indigenous populations, but there have been few studies of the effectiveness of screening and treatment in primary health care. Over 24 months, we tested whether a model of service-wide support could increase screening and any alcohol treatment. Design Cluster-randomized trial with 24-month implementation (12 months active, 12 months maintenance). Setting Australian Aboriginal Community Controlled primary care services. Participants Twenty-two services (83 032 clients) that use Communicare practice software and see at least 1000 clients annually, randomized to the treatment arm or control arm. Intervention and comparator Multi-faceted early support model versus a comparator of waiting-list control (11 services). Measurements A record (presence = 1, absence = 0) of: (i) Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) screening (primary outcome), (ii) any-treatment and (iii) brief intervention. We received routinely collected practice data bimonthly over 3 years (1-year baseline, 1-year implementation, 1-year maintenance). Multi-level logistic modelling was used to compare the odds of each outcome before and after implementation. Findings The odds of being screened within any 2-month reference period increased in both arms post-implementation, but the increase was nearly eight times greater in early-support services [odds ratio (OR) = 7.95, 95% confidence interval (CI) = 4.04–15.63, P < 0.001]. The change in odds of any treatment in early support was nearly double that of waiting-list controls (OR = 1.89, 95% CI = 1.19–2.98, P = 0.01) but was largely driven by decrease in controls. There was no clear evidence of difference between groups in the change in the odds of provision of brief intervention (OR = 1.95, 95% CI = 0.53–7.17, P = 0.32). Conclusions An early support model designed to aid routine implementation of alcohol screening and treatment in Aboriginal health services resulted in improvement of Alcohol Use Disorders Identification Test—Consumption screening rates over 24 months of implementation, but the effect on treatment was less clear

Supporting Aboriginal Community Controlled Health Services to deliver alcohol care : Protocol for a cluster randomised controlled trial

Introduction Indigenous peoples who have experienced colonisation or oppression can have a higher prevalence of alcohol-related harms. In Australia, Aboriginal Community Controlled Health Services (ACCHSs) offer culturally accessible care to Aboriginal and Torres Strait Islander (Indigenous) peoples. However there are many competing health, socioeconomic and cultural client needs. Methods and analysis A randomised cluster wait-control trial will test the effectiveness of a model of tailored and collaborative support for ACCHSs in increasing use of alcohol screening (with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)) and of treatment provision (brief intervention, counselling or relapse prevention medicines). Setting Twenty-two ACCHSs across Australia. Randomisation Services will be stratified by remoteness, then randomised into two groups. Half receive support soon after the trial starts (intervention or ‘early support’); half receive support 2 years later (wait-control or ‘late support’). The support Core support elements will be tailored to local needs and include: support to nominate two staff as champions for increasing alcohol care; a national training workshop and bimonthly teleconferences for service champions to share knowledge; onsite training, and bimonthly feedback on routinely collected data on screening and treatment provision. Outcomes and analysis Primary outcome is use of screening using AUDIT-C as routinely recorded on practice software. Secondary outcomes are recording of brief intervention, counselling, relapse prevention medicines; and blood pressure, gamma glutamyltransferase and HbA1c. Multi-level logistic regression will be used to test the effectiveness of support. Ethics and dissemination Ethical approval has been obtained from eight ethics committees: the Aboriginal Health and Medical Research Council of New South Wales (1217/16); Central Australian Human Research Ethics Committee (CA-17-2842); Northern Territory Department of Health and Menzies School of Health Research (2017-2737); Central Queensland Hospital and Health Service (17/QCQ/9); Far North Queensland (17/QCH/45-1143); Aboriginal Health Research Ethics Committee, South Australia (04-16-694); St Vincent’s Hospital (Melbourne) Human Research Ethics Committee (LRR 036/17); and Western Australian Aboriginal Health Ethics Committee (779). Trial registration number ACTRN12618001892202; Pre-results

Greenland freshwater pathways in the sub-Arctic Seas from model experiments with passive tracers

Author Posting. © American Geophysical Union, 2016. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 121 (2016): 877–907, doi:10.1002/2015JC011290.Accelerating since the early 1990s, the Greenland Ice Sheet mass loss exerts a significant impact on thermohaline processes in the sub-Arctic seas. Surplus freshwater discharge from Greenland since the 1990s, comparable in volume to the amount of freshwater present during the Great Salinity Anomaly events, could spread and accumulate in the sub-Arctic seas, influencing convective processes there. However, hydrographic observations in the Labrador Sea and the Nordic Seas, where the Greenland freshening signal might be expected to propagate, do not show a persistent freshening in the upper ocean during last two decades. This raises the question of where the surplus Greenland freshwater has propagated. In order to investigate the fate, pathways, and propagation rate of Greenland meltwater in the sub-Arctic seas, several numerical experiments using a passive tracer to track the spreading of Greenland freshwater have been conducted as a part of the Forum for Arctic Ocean Modeling and Observational Synthesis effort. The models show that Greenland freshwater propagates and accumulates in the sub-Arctic seas, although the models disagree on the amount of tracer propagation into the convective regions. Results highlight the differences in simulated physical mechanisms at play in different models and underscore the continued importance of intercomparison studies. It is estimated that surplus Greenland freshwater flux should have caused a salinity decrease by 0.06–0.08 in the sub-Arctic seas in contradiction with the recently observed salinification (by 0.15–0.2) in the region. It is surmised that the increasing salinity of Atlantic Water has obscured the freshening signal.NSERC. Grant Numbers RGPIN 227438-09, RGPIN 04357 and RGPCC 433898; RFBR. Grant Number 13-05-00480, 14-05-00730, and 15-05-02457; NSF Grant Number: PLR-0804010, PLR-1313614, and PLR-12037202016-07-2

Megacity and local contributions to regional air pollution : An aircraft case study over London

In July 2017 three research flights circumnavigating the megacity of London were conducted as a part of the STANCO training school for students and early career researchers organised by EUFAR (European Facility for Airborne Research). Measurements were made from the UK's Facility for Airborne Atmospheric Measurements (FAAM) BAe-146-301 atmospheric research aircraft with the aim to sample, characterise and quantify the impact of megacity outflow pollution on air quality in the surrounding region. Conditions were extremely favourable for airborne measurements, and all three flights were able to observe clear pollution events along the flight path. A small change in wind direction provided sufficiently different air mass origins over the 2 d such that a distinct pollution plume from London, attributable marine emissions and a double-peaked dispersed area of pollution resulting from a combination of local and transported emissions were measured. We were able to analyse the effect of London emissions on air quality in the wider region and the extent to which local sources contribute to pollution events. The background air upwind of London was relatively clean during both days; concentrations of CO were 88-95 ppbv, total (measured) volatile organic compounds (VOCs) were 1.6-1.8 ppbv and NOx was 0.7- 0.8 ppbv. Downwind of London, we encountered elevations in all species with CO>100 ppbv, VOCs 2.8-3.8 ppbv, CH4>2080 ppbv and NOx>4 ppbv, and peak concentrations in individual pollution events were higher still. Levels of O3 were inversely correlated with NOx during the first flight, with O3 concentrations of 37 ppbv upwind falling to 26 ppbv in the well-defined London plume. Total pollutant fluxes from London were estimated through a vertical plane downwind of the city. Our calculated CO2 fluxes are within the combined uncertainty of those estimated previously, but there was a greater disparity in our estimates of CH4 and CO. On the second day, winds were lighter and downwind O3 concentrations were elevated to 39-43 ppbv (from 32 to 35 ppbv upwind), reflecting the contribution of more aged pollution to the regional background. Elevations in pollutant concentrations were dispersed over a wider area than the first day, although we also encountered a number of clear transient enhancements from local sources. This series of flights demonstrated that even in a region of megacity outflow, such as the south-east of the UK, local fresh emissions and more distant UK sources of pollution can all contribute substantially to pollution events. In the highly complex atmosphere around a megacity where a high background level of pollution mixes with a variety of local sources at a range of spatial and temporal scales and atmospheric dynamics are further complicated by the urban heat island, the use of pollutant ratios to track and determine the ageing of air masses may not be valid. The individual sources must therefore all be well-characterised and constrained to understand air quality around megacities such as London. Research aircraft offer that capability through targeted sampling of specific sources and longitudinal studies monitoring trends in emission strength and profiles over time

Realistic Equations of State for the Primeval Universe

Early universe equations of state including realistic interactions between constituents are built up. Under certain reasonable assumptions, these equations are able to generate an inflationary regime prior to the nucleosynthesis period. The resulting accelerated expansion is intense enough to solve the flatness and horizon problems. In the cases of curvature parameter \kappa equal to 0 or +1, the model is able to avoid the initial singularity and offers a natural explanation for why the universe is in expansion.Comment: 32 pages, 5 figures. Citations added in this version. Accepted EPJ

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity