Detection of early osteogenic commitment in primary cells using Raman spectroscopy

Major challenges in the development of novel implant surfaces for artificial joints include osteoblast heterogeneity and the lack of a simple and sensitive in vitro assay to measure early osteogenic responses. Raman spectroscopy is a label-free, non-invasive and non-destructive vibrational fingerprinting optical technique that is increasingly being applied to detect biochemical changes in cells. In this study Raman spectroscopy has been used to obtain bone cell-specific spectral signatures and to identify any changes therein during osteoblast commitment and differentiation of primary cells in culture. Murine calvarial osteoblasts (COBs) were extracted and cultured and studied by Raman spectroscopy over a 14 day culture period. Distinct osteogenic Raman spectra were identified after 3 days of culture with strong bands detected for mineral: phosphate ν3 (1030 cm−1) and B-type carbonate (1072 cm−1), DNA (782 cm−1) and collagen matrix (CH2 deformation at 1450 cm−1) and weaker phosphate bands (948 and 970 cm−1). Early changes were detected by Raman spectroscopy compared to a standard enzymatic alkaline phosphatase (ALP) assay and gene expression analyses over this period. Proliferation of COBs was confirmed by fluorescence intensity measurements using the Picogreen dsDNA reagent. Changes in ALP levels were evident only after 14 days of culture and mRNA expression levels for ALP, Col1a1 and Sclerostin remained constant during the culture period. Sirius red staining for collagen deposition also revealed little change until day 14. In contrast Raman spectroscopy revealed the presence of amorphous calcium phosphate (945–952 cm−1) and carbonated apatite (957–962 cm−1) after only 3 days in culture and octacalcium phosphate (970 cm−1) considered a transient mineral phase, was detected after 5 days of COBs culture. PCA analysis confirmed clear separation between time-points. This study highlights the potential of Raman spectroscopy to be utilised for the early and specific detection of proliferation and differentiation changes in primary cultures of bone cells

Variable temperature study of the crystal and magnetic structures of the giant magnetoresistant materials LMnAsO (L=La, Nd)

Peer reviewedPublisher PD

A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study

Objective: The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection. Design and Setting: This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom. Participants: Participants were 36 antiretroviral treatment naive HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3). Interventions: Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day ( 12 participants) or 9 MIU/day ( 12 participants) or no treatment ( 12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk. Outcome Measures: Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis. Results: Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 ( both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3 - 181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) ( p = 0.008) and 128.4 cells/mm(3) ( p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow- up ( 95% CI for difference, - 0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy. Conclusions: In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels

Risk prediction tools for cancer in primary care.

This is the final version of the article. Available from the publisher via the DOI in this record.Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed

Effect of FET geometry on charge ordering of transition metal oxides

We examine the effect of an FET geometry on the charge ordering phase diagram of transition metal oxides using numerical simulations of a semiclassical model including long-range Coulomb fields, resulting in nanoscale pattern formation. We find that the phase diagram is unchanged for insulating layers thicker than approximately twice the magnetic correlation length. For very thin insulating layers, the onset of a charge clump phase is shifted to lower values of the strength of the magnetic dipolar interaction, and intermediate diagonal stripe and geometric phases can be suppressed. Our results indicate that, for sufficiently thick insulating layers, charge injection in an FET geometry can be used to experimentally probe the intrinsic charge ordering phases in these materials.Comment: 4 pages, 4 postscript figure

Risk prediction models for melanoma: a systematic review.

Melanoma incidence is increasing rapidly worldwide among white-skinned populations. Earlier diagnosis is the principal factor that can improve prognosis. Defining high-risk populations using risk prediction models may help targeted screening and early detection approaches. In this systematic review, we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict risk of developing cutaneous melanoma. A total of 4,141 articles were identified from the literature search and six through citation searching. Twenty-five risk models were included. Between them, the models considered 144 possible risk factors, including 18 measures of number of nevi and 26 of sun/UV exposure. Those most frequently included in final risk models were number of nevi, presence of freckles, history of sunburn, hair color, and skin color. Despite the different factors included and different cutoff values for sensitivity and specificity, almost all models yielded sensitivities and specificities that fit along a summary ROC with area under the ROC (AUROC) of 0.755, suggesting that most models had similar discrimination. Only two models have been validated in separate populations and both also showed good discrimination with AUROC values of 0.79 (0.70-0.86) and 0.70 (0.64-0.77). Further research should focus on validating existing models rather than developing new ones.This report is independent research arising from a Clinician Scientist award supported by the National Institute for Health Research (RG 68235) and J Usher-Smith is funded by a National Institute for Health Research Clinical LectureshipThis is the author accepted manuscript. The advanced access published version can be found on the publisher's website at: http://cebp.aacrjournals.org/content/early/2014/06/03/1055-9965.EPI-14-0295.abstrac

Infrared Lightcurves of Near Earth Objects

We present lightcurves and derive periods and amplitudes for a subset of 38 near earth objects (NEOs) observed at 4.5 microns with the IRAC camera on the the Spitzer Space Telescope, many of them having no previously reported rotation periods. This subset was chosen from about 1800 IRAC NEO observations as having obvious periodicity and significant amplitude. For objects where the period observed did not sample the full rotational period, we derived lower limits to these parameters based on sinusoidal fits. Lightcurve durations ranged from 42 to 544 minutes, with derived periods from 16 to 400 minutes. We discuss the effects of lightcurve variations on the thermal modeling used to derive diameters and albedos from Spitzer photometry. We find that both diameters and albedos derived from the lightcurve maxima and minima agree with our previously published results, even for extreme objects, showing the conservative nature of the thermal model uncertainties. We also evaluate the NEO rotation rates, sizes, and their cohesive strengths.Comment: 16 pages, 4 figures, 3 tables, to appear in the Astrophysical Journal Supplement Serie

ExploreNEOs VIII: Dormant Short-Period Comets in the Near-Earth Asteroid Population

We perform a search for dormant comets, asteroidal objects of cometary origin, in the near-Earth asteroid (NEA) population based on dynamical and physical considerations. Our study is based on albedos derived within the ExploreNEOs program and is extended by adding data from NEOWISE and the Akari asteroid catalog. We use a statistical approach to identify asteroids on orbits that resemble those of short-period near-Earth comets using the Tisserand parameter with respect to Jupiter, the aphelion distance, and the minimum orbital intersection distance with respect to Jupiter. From the sample of NEAs on comet-like orbits, we select those with a geometric albedo $p_V \leq 0.064$ as dormant comet candidates, and find that only $\sim$50% of NEAs on comet-like orbits also have comet-like albedos. We identify a total of 23 NEAs from our sample that are likely to be dormant short-period near-Earth comets and, based on a de-biasing procedure applied to the cryogenic NEOWISE survey, estimate both magnitude-limited and size-limited fractions of the NEA population that are dormant short-period comets. We find that 0.3-3.3% of the NEA population with $H \leq 21$, and $9^{+2}_{-5}$% of the population with diameters $d \geq 1$ km, are dormant short-period near-Earth comets.Comment: 23 pages, 2 figures, 2 tables; accepted for publication in A

Dynamics of lattice pinned charge stripes

We study the transversal dynamics of a charged stripe (quantum string) and show that zero temperature quantum fluctuations are able to depin it from the lattice. If the hopping amplitude t is much smaller than the string tension J, the string is pinned by the underlying lattice. At t>>J, the string is depinned and allowed to move freely, if we neglect the effect of impurities. By mapping the system onto a 1D array of Josephson junctions, we show that the quantum depinning occurs at t/J = 2 / pi^2. Besides, we exploit the relation of the stripe Hamiltonian to the sine-Gordon theory and calculate the infrared excitation spectrum of the quantum string for arbitrary t/J values.Comment: 4 pages, 2 figure

The Discovery of Cometary Activity in Near-Earth Asteroid (3552) Don Quixote

The near-Earth object (NEO) population, which mainly consists of fragments from collisions between asteroids in the main asteroid belt, is thought to include contributions from short-period comets as well. One of the most promising NEO candidates for a cometary origin is near-Earth asteroid (3552) Don Quixote, which has never been reported to show activity. Here we present the discovery of cometary activity in Don Quixote based on thermal-infrared observations made with the Spitzer Space Telescope in its 3.6 and 4.5 {\mu}m bands. Our observations clearly show the presence of a coma and a tail in the 4.5 {\mu}m but not in the 3.6 {\mu}m band, which is consistent with molecular band emission from CO2. Thermal modeling of the combined photometric data on Don Quixote reveals a diameter of 18.4 (-0.4/+0.3) km and an albedo of 0.03 (-0.01/+0.02), which confirms Don Quixote to be the third-largest known NEO. We derive an upper limit on the dust production rate of 1.9 kg s^-1 and derive a CO2 gas production rate of (1.1+-0.1)10^26 molecules s^-1. Spitzer IRS spectroscopic observations indicate the presence of fine-grained silicates, perhaps pyroxene rich, on the surface of Don Quixote. Our discovery suggests that CO2 can be present in near-Earth space over a long time. The presence of CO2 might also explain that Don Quixote's cometary nature remained hidden for nearly three decades.Comment: 40 pages, 8 figures, accepted by Ap