Development and Characterization of Gallium-Doped Bioactive Glasses for Potential Bone Cancer Applications

In this study, we have developed a series of novel gallium oxide doped bioactive glasses to specifically target osteosarcoma cells while aiding new bone formation. The results show that osteosarcoma (Saos-2) cell death is induced through the addition of gallium oxide. Relative to the gallium-free control glass (0% Ga) glasses containing 1, 2, and 3% Ga decreased Saos-2 cell viability in a dose dependent manner. After 72 h in media preconditioned with 3% Ga Saos-2 cell viability was reduced by over 50%. Corresponding studies undertaken on primary normal human osteoblast cells (NHOst) demonstrated no adverse effects to the gallium containing glasses. Hydroxyapatite formation was observed for all glasses when exposed to simulated body fluid

Improving our understanding of metal implant failures: Multiscale chemical imaging of exogenous metals in ex-vivo biological tissues

Biological exposures to micro- and nano-scale exogenous metal particles generated as a consequence of in-service degradation of orthopaedic prosthetics can result in severe adverse tissues reactions. However, individual reactions are highly variable and are not easily predicted, due to in part a lack of understanding of the speciation of the metal-stimuli which dictates cellular interactions and toxicity. Investigating the chemistry of implant derived metallic particles in biological tissue samples is complicated by small feature sizes, low concentrations and often a heterogeneous speciation and distribution. These challenges were addressed by developing a multi-scale two-dimensional X-ray absorption spectroscopic (XAS) mapping approach to discriminate sub-micron changes in particulate chemistry within ex-vivo tissues associated with failed CoCrMo total hip replacements (THRs). As a result, in the context of THRs, we demonstrate much greater variation in Cr chemistry within tissues compared with previous reports. Cr compounds including phosphate, hydroxide, oxide, metal and organic complexes were observed and correlated with Co and Mo distributions. This variability may help explain the lack of agreement between biological responses observed in experimental exposure models and clinical outcomes. The multi-scale 2D XAS mapping approach presents an essential tool in discriminating the chemistry in dilute biological systems where speciation heterogeneity is expected. Significance: Metal implants are routinely used in healthcare but may fail following degradation in the body. Although specific implants can be identified as ‘high-risk’, our analysis of failures is limited by a lack of understanding of the chemistry of implant metals within the peri-prosthetic milieu. A new approach to identify the speciation and variability in speciation at sub-micron resolution, of dilute exogenous metals within biological tissues is reported; applied to understanding the failure of metallic (CoCrMo) total-hip-replacements widely used in orthopedic surgery. Much greater variation in Cr chemistry was observed compared with previous reports and included phosphate, hydroxide, oxide, metal and organic complexes. This variability may explain lack of agreement between biological responses observed in experimental exposure models and clinical outcomes

Implications of X-ray beam profiles on qualitative and quantitative synchrotron micro-focus X-ray fluorescence microscopy

Synchrotron radiation X-ray fluorescence microscopy is frequently used to investigate the spatial distribution of elements within a wide range of samples. Interrogation of heterogeneous samples that contain large concentration ranges has the potential to produce image artefacts due to the profile of the X-ray beam. The presence of these artefacts and the distribution of flux within the beam profile can significantly affect qualitative and quantitative analyses. Two distinct correction methods have been generated by referencing the beam profile itself or by employing an adaptive-thresholding procedure. Both methods significantly improve qualitative imaging by removing the artefacts without compromising the low-intensity features. The beam-profile correction method improves quantitative results but requires accurate two-dimensional characterization of the X-ray beam profile

Photo-polymerisation variables influence the structure and subsequent thermal response of dental resin matrices

Objective The structure of the polymer phase of dental resin-based-composites is highly sensitive to photo-polymerisation variables. The objective of this study was to understand how different polymer structures, generated with different photo-polymerisation protocols, respond to thermal perturbation. Methods Experimental resins were prepared from a series of Bis-GMA/TEGDMA blends (40/60, 50/50 and 60/40 wt.%), with either Camphorquinone/DMAEMA or Lucirin TPO as the photo-initiator system. Resins were photo-polymerised, in a disc geometry, at either relatively ‘high’ (3000 mW cm−2 for 6 s) or ‘low’ (300 mW cm−2 for 60 s) irradiances ensuring matched radiant exposures (18 J cm−2). Specimens were heated, from 20−160 °C at a rate of 5 °C min−1, whilst simultaneous synchrotron X-ray scattering measurements were taken at 5 °C increments to determine changes in polymer chain segment extension and medium-range order as a function of temperature. For each unique resin composition (n = 3), differential scanning calorimetry was used to measure glass transition temperatures using the same heating protocol. A paired t-test was used to determine significant differences in the glass transition temperature between irradiance protocols and photo-initiator chemistry at ɑ = 0.05. Results Resins pre-polymerised through the use of TPO and or high irradiances demonstrated a reduced rate of chain extension indicative of lower thermal expansion and a larger decrease in relative order when heated below the glass transition temperature. Above the transition temperature, differences in the rate of chain extension were negligible, but slower converted systems showed greater relative order. There was no significant difference in the glass transition temperature between different photo-initiator systems or irradiance protocols. Significance The evolution of chain extension and medium-range order during heating is dependent on the initial polymer structure which is influenced by photo-polymerisation variables. Less ordered systems, generated at faster rates of reactive group conversion displayed reduced chain extension below the glass transition temperature and maintained lower order throughout heating

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS

OBJECTIVE: Pulmonary hypertension is a characteristic feature of acute respiratory distress syndrome (ARDS) and contributes to mortality. Administration of sildenafil in ambulatory patients with pulmonary hypertension improves oxygenation and ameliorates pulmonary hypertension. Our aim was to determine whether sildenafil is beneficial for patients with ARDS. DESIGN: Prospective, open-label, multicenter, interventional cohort study. SETTING: Medical-surgical ICU of two university hospitals. PATIENTS: Ten consecutive patients meeting the NAECC criteria for ARDS. INTERVENTIONS: A single dose of 50 mg sildenafil citrate administered via a nasogastric tube. MAIN RESULTS: Administration of sildenafil in patients with ARDS decreased mean pulmonary arterial pressure from 25 to 22 mmHg (P = 0.022) and pulmonary artery occlusion pressure from 16 to 13 mmHg (P = 0.049). Systemic mean arterial pressures were markedly decreased from 81 to 75 mmHg (P = 0.005). Sildenafil did not improve pulmonary arterial oxygen tension, but resulted in a further increase in the shunt fraction. CONCLUSION: Although sildenafil reduced pulmonary arterial pressures during ARDS, the increased shunt fraction and decreased arterial oxygenation render it unsuitable for the treatment of patients with ARD

Do longer consultations improve the management of psychological problems in general practice? A systematic literature review

<p>Abstract</p> <p>Background</p> <p>Psychological problems present a huge burden of illness in our community and GPs are the main providers of care. There is evidence that longer consultations in general practice are associated with improved quality of care; but this needs to be balanced against the fact that doctor time is a limited resource and longer consultations may lead to reduced access to health care.</p> <p>The aim of this research was to conduct a systematic literature review to determine whether management of psychological problems in general practice is associated with an increased consultation length and to explore whether longer consultations are associated with better health outcomes for patients with psychological problems.</p> <p>Methods</p> <p>A search was conducted on Medline (Ovid) databases up to7 June 2006. The following search terms, were used:</p> <p>general practice or primary health care (free text) or family practice (MeSH)</p> <p>AND consultation length or duration (free text) or time factors (MeSH)</p> <p>AND depression or psychological problems or depressed (free text).</p> <p>A similar search was done in Web of Science, Pubmed, Google Scholar, and Cochrane Library and no other papers were found.</p> <p>Studies were included if they contained data comparing consultation length and management or detection of psychological problems in a general practice or primary health care setting. The studies were read and categories developed to enable systematic data extraction and synthesis.</p> <p>Results</p> <p>29 papers met the inclusion criteria. Consultations with a recorded diagnosis of a psychological problem were reported to be longer than those with no recorded psychological diagnosis. It is not clear if this is related to the extra time or the consultation style. GPs reported that time pressure is a major barrier to treating depression. There was some evidence that increased consultation length is associated with more accurate diagnosis of psychological problems.</p> <p>Conclusion</p> <p>Further research is needed to elucidate the factors in longer consultations that are associated with greater detection of psychological problems, and to determine the association between the detection of psychological problems and the attitude, gender, age or training of the GP and the age, gender and socioeconomic status of the patient. These are important considerations if general practice is to deal more effectively with people with psychological problems.</p