Does the advent of modern implant systems and the refinement of free flap technique negate the effect of radiotherapy in oral cancer dental implant based oral rehabilitation

Aim: The aim of this study was to see whether the advent of modern implant systems, and the refinement of free flap techniques, negate the effect of radiotherapy in patients with oral cancer who undergo dental implant–based oral rehabilitation. Materials and method: A retrospective study was performed to look at the success rates of implants placed in all patients, in a 3 year period at the Queen Elizabeth Hospital, Birmingham. Survival rates in irradiated patients were compared with success rates in patients who did receive radiotherapy. Results and conclusions: The rate of failure is comparable in the no radiotherapy group (1.12%) and post-radiotherapy group (1.76%). Our study shows that there was no significant difference in survival when implants were placed in native, grafted bone or in free flap reconstructions in irradiated head and neck cancer patients. Ultimately, the current evidence is not strong enough to prove whether the advent of modern implants systems, and the refinement of free flap techniques, does negate the effect of radiotherapy in patients with oral cancer undergoing dental implant–based oral rehabilitation. There is a need to perform a prospective clinical trial to observe clinical outcomes in both patients who have received radiotherapy and those who have not received radiotherap

The Galaxy Structure-Redshift Relationship

There exists a gradual, but persistent, evolutionary effect in the galaxy population such that galaxy structure and morphology change with redshift. This galaxy structure-redshift relationship is such that an increasingly large fraction of all bright and massive galaxies at redshifts 2 < z < 3 are morphologically peculiar at wavelengths from rest-frame ultraviolet to rest-frame optical. There are however examples of morphologically selected spirals and ellipticals at all redshifts up to z ~ 3. At lower redshift, the bright galaxy population smoothly transforms into normal ellipticals and spirals. The rate of this transformation strongly depends on redshift, with the swiftest evolution occurring between 1 < z < 2. This review characterizes the galaxy structure-redshift relationship, discusses its various physical causes, and how these are revealing the mechanisms responsible for galaxy formation.Comment: 20 pages, 8 figures. Invited Review to appear in "Penetrating Bars Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes A New Note", ed. D. Block et a

The analysis of relapse-free survival curves: implications for evaluating intensive systemic adjuvant treatment regimens for breast cancer

Results of adjuvant dose intensification studies in patients with localised breast cancer have raised questions regarding the clinical usefulness of this treatment strategy. Here, we develop and fit a natural history model for the time to clinical tumour recurrence as a function of the number of involved lymph nodes, and derive plausible predictions of the effects of dose intensification under various conditions. The time to tumour recurrence is assumed to depend on the residual postoperative micrometastatic burden of tumour, the fractional reduction of residual tumour burden (RTB) by treatment, and the rate of regrowth of the RTB to a clinically detectable size. It is assumed that a proportion of micrometastatic tumours are unresponsive to adjuvant chemotherapy even at maximal dose intensity. Data fitted included the San Antonio Cancer Institute (SACI) database of untreated patients, and CALGB #9082, a study comparing a highly intensive and moderately intensity adjuvant regimen in patients with 10+ positive axillary nodes. The proportion of tumours unresponsive to maximally intensive adjuvant treatment is estimated to be 48% (29–67%). The estimated log kill for intermediate-dose therapy from CALGB #9082 was 6.5 logs, compared with 9 logs or greater for high-dose therapy. The model is consistent with a modest but nonnegligible advantage of dose intensification compared with standard therapies in patients with sensitive tumours who have 10+ positive axillary nodes, and suggests that much of this clinical benefit could be achieved using intermediate levels of treatment intensification. The model further suggests that, in patients with fewer than 10 involved axillary nodes, any advantage of treatment intensification over standard therapy would be much reduced, because in patients with smaller tumour burdens of sensitive tumour, a larger proportion of cures achievable with intensified therapy could be achieved as well with standard therapy

Selectivity of the photosensitiser Tookad® for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions

Quantifying Morphological Evolution from Low to High Redshifts

Establishing the morphological history of ordinary galaxies was one of the original goals for the Hubble Space Telescope, and remarkable progress toward achieving this this goal has been made. How much of this progress has been at the expense of the Hubble sequence? As we probe further out in redshift space, it seems time to re-examine the underlying significance of Hubble's tuning fork in light of the the spectacular and often bizarre morphological characteristics of high redshift galaxies. The aim of this review is to build a morphological bridge between high-redshift and low-redshift galaxy populations, by using quantitative morphological measures to determine the maximum redshift for which the Hubble sequence provides a meaningful description of the galaxy population. I will outline the various techniques used to quantify high-redshift galaxy morphology, highlight the aspects of the Hubble sequence being probed by these techniques, and indicate what is getting left behind. I will argue that at higher redshifts new techniques (and new ideas) that place less emphasis on classical morphology and more emphasis on the link between morphology and resolved stellar populations are needed in order to probe the evolutionary history of high-redshift galaxies

Tumour Cannabinoid CB1 Receptor and Phosphorylated Epidermal Growth Factor Receptor Expression Are Additive Prognostic Markers for Prostate Cancer

BACKGROUND: In cultured prostate cancer cells, down-regulation of epidermal growth factor receptor (EGFR) has been implicated in mediating the antiproliferative effect of the endogenous cannabinoid (CB) ligand anandamide. Using a well-characterised cohort of prostate cancer patients, we have previously reported that expression levels of phosphorylated EGFR (pEGFR-IR) and CB(1) receptor (CB(1)IR) in tumour tissue at diagnosis are markers of disease-specific survival, but it is not known whether the two markers interact in terms of their influence on disease severity at diagnosis and disease outcome. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for voiding difficulties was used. Scores for both tumour CB(1)IR and pEGFR-IR were available in the database. Of these, 235 had been followed by expectancy until the appearance of metastases. For patients scored for both parameters, Cox proportional-hazards regression analyses using optimal cut-off scores indicated that the two measures provided additional diagnostic information not only to each other, but to that provided by the tumour stage and the Gleason score. When the cases were divided into subgroups on the basis of these cut-off scores, the patients with both CB(1)IR and pEGFR-IR scores above their cut-off had a poorer disease-specific survival and showed a more severe pathology at diagnosis than patients with high pEGFR-IR scores but with CB(1)IR scores below the cut-off. CONCLUSIONS/SIGNIFICANCE: These data indicate that a high tumour CB(1) receptor expression at diagnosis augments the deleterious effects of a high pEGFR expression upon disease-specific survival

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Capacitative calcium influx and proliferation of human osteoblastic-like MG-63 cells

Adult bone tissue is continuously being remodelled and bone mass is maintained by a balance between osteoclastic bone resorption and osteoblastic bone formation. Alteration of osteoblastic cell proliferation may account in part for lack of balance between these two processes in bone loss of osteoporosis. There is calcium (Ca2+) control in numerous cellular functions; however, involvement of capacitative Ca2+ entry (CCE) in proliferation of bone cells is less well investigated. OBJECTIVES: The study described here was aimed to investigate roles of CCE in the proliferation of osteoblast-like MG-63 cells. MATERIALS AND METHODS: Pharmacological characterizations of CCE were undertaken in parallel, with evaluation of the expression of transient receptor potential canonical (TRPC) channels and of cell proliferation. RESULTS: Intracellular Ca2+ store depletion by thapsigargin induced CCE in MG-63 cells; this was characterized by a rapid transient increase of intracellular Ca2+ followed by significant CCE, induced by conditions that stimulated cell proliferation, namely serum and platelet-derived growth factor. Inhibitors of store-operated Ca2+ channels (2-APB and SKF-96365) prevented CCE, while voltage-dependent Ca2+ channel blockers had no effect. Expression of various TRPC channels was shown in the cells, some having been shown to be responsible for CCE. Voltage-dependent Ca2+ channel blockers had no effect on osteoblast proliferation while thapsigargin, 2-APB and SKF-96395, inhibited it. Cell cycle analysis showed that 2-APB and SKF-96395 lengthen the S and G2/M phases, which would account for the reduction in cell proliferation. CONCLUSIONS: Our results indicate that CCE, likely attributed to the activation of TRPCs, might be the main route for Ca2+ influx involved in osteoblast proliferation

Longitudinal changes in sedentary time and physical activity during adolescence

BACKGROUND: Low levels of physical activity and high time spent in sedentary activities have been associated with unfavourable health outcomes in adolescents. During adolescence, physical activity declines and sedentary time increases, however little is known about whether the magnitude of these changes differs within or between school-time, after-school time, or at weekends. METHODS: Adolescents (n = 363) participating in the PEACH (Personal and Environmental Associations with Children’s Health) project provided accelerometer data at 12 and 15 years of age. Data were collected in 2008/2009 and 2012/2013. Time spent sedentary (<100 cpm), in light physical activity (LPA (100-2295 cpm) and in moderate to vigorous physical activity (MVPA: ≥ 2296 cpm) were generated for school-time, after-school time and for weekends using school-specific start and finish times. All data were analysed in 2014. RESULTS: The proportion of time spent sedentary significantly increased during school (+8.23%, 95% CI = 7.35 to 9.13), after-school (+6.99%, 95% CI = 5.91 to 8.07) and at weekends (+6.86%, 95% CI = 5.10 to 8.62). A parallel decrease was found in the proportion of time spent in LPA during school (-7.62%, 95% CI = -8.26 to -6.98), after-school (-7.01%, 95% CI = -7.74 to -6.28) and at weekends (-6.72%, 95% CI = -7.80 to -5.65). The proportion of time spent in MVPA remained relatively stable during school (-0.64, 95% CI = -1.11 to -0.18), after-school (0.04%, 95% CI = -0.58 to 0.67) and at weekends (-0.14%, 95% CI = -1.18 to 0.90). CONCLUSIONS: Objectively measured sedentary time increased between 12 and 15 years of age during-school, after-school, and at weekends, suggesting that interventions aiming to reduce the age-associated changes in sedentary time are needed in all three time contexts. Future work should identify which sedentary activities change more than others to inform interventions which aim to minimise the increase in time spent sedentary during adolescence