Global Campus: learning to walk with webbed feet

Universities wishing to expand their provision beyond their local catchment areas need to consider whether to bring the students to the tuition or take the tuition to the students. Current-day educational and information technologies make the latter option a much more achievable prospect than it has been in the past. Nevertheless, careful consideration needs to be given to the nature of the distance-learning students' learning experiences and the extent to which these may be comparable with those of the local students. These matters are considered in this paper against the background of the Global Campus project whereby Middlesex University's School of Computing Science sought to take its initial steps in distance-learning provision

Modeling the dosimetry of organ-at-risk in head and neck IMRT planning: An intertechnique and interinstitutional study

Purpose: To build a statistical model to quantitatively correlate the anatomic features of structures and the corresponding dose-volume histogram (DVH) of head and neck (HN) Tomotherapy (Tomo) plans. To study if the model built upon one intensity modulated radiation therapy (IMRT) technique (such as conventional Linac) can be used to predict anticipated organs-at-risk (OAR) DVH of patients treated with a different IMRT technique (such as Tomo). To study if the model built upon the clinical experience of one institution can be used to aid IMRT planning for another institution

Definitive hypofractionated radiotherapy for early glottic carcinoma: experience of 55Gy in 20 fractions

Introduction: A wide variety of fractionation schedules have been employed for the treatment of early glottic cancer. The aim is to report our 10-year experience of using hypofractionated radiotherapy with 55Gy in 20 fractions at 2.75Gy per fraction. Methods: Patients treated between 2004 and 2013 with definitive radiotherapy to a dose of 55Gy in 20 fractions over 4 weeks for T1/2 N0 squamous cell carcinoma of the glottis were retrospectively identified. Patients with prior therapeutic minor surgery (eg. laser stripping, cordotomy) were included. The probabilities of local control, ultimate local control (including salvage surgery), regional control, cause specific survival (CSS) and overall survival (OS) were calculated. Results: One hundred thirty-two patients were identified. Median age was 65 years (range 33–89). Median follow up was 72 months (range 7–124). 50 (38 %), 18 (14 %) and 64 (48 %) of patients had T1a, T1b and T2 disease respectively. Five year local control and ultimate local control rates were: overall - 85.6 % and 97.3 % respectively, T1a - 91.8 % and 100 %, T1b - 81.6 and 93.8 %, and T2 - 80.9 % and 95.8 %. Five year regional control, CSS and OS rates were 95.4 %, 95.7 % and 78.8 % respectively. There were no significant associations of covariates (e.g. T-stage, extent of laryngeal extension, histological grade) with local control on univariate analysis. Only increasing age and transglottic extension in T2 disease were significantly associated with overall survival (both p <0.01). Second primary cancers developed in 17 % of patients. 13 (9.8 %) of patients required enteral tube feeding support during radiotherapy; no patients required long term enteral nutrition. One patient required a tracheostomy due to a non-functioning larynx on long term follow up. Conclusions: Hypofractionated radiation therapy with a dose of 55Gy in 20 fractions for early stage glottic cancer provides high rates of local control with acceptable toxicity

Positron Emission Tomography and Stage Migration in Head and Neck Cancer

IMPORTANCE: Since 2001, there has been a rapid adoption of positron emission tomography (PET) for diagnosis and American Joint Committee on Cancer (AJCC) staging of head and neck cancer (HNC) without data describing improved clinical outcomes. OBJECTIVE: To determine the association between increased use of PET and stage and/or survival for patients with HNC in the managed care environment. DESIGN, SETTING, AND PARTICIPANTS: Adult patients diagnosed as having HNC (n = 958) from 2000 to 2008 at 4 integrated health systems were identified via tumor registries linked to administrative data. The AJCC stage distribution, patient and treatment characteristics, and survival between pre-PET era (2000-2004) vs PET era (2005-2008) and use of PET vs no use of PET during the PET era were compared. The AJCC stages were categorized to represent localized (stage I or II), locally advanced (stage III, IVA, or IVB), and metastatic (stage IVC) disease. INTERVENTIONS: Treatments were determined by billing codes for surgery, radiation treatment, and chemotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome for this study was the use of PET. Secondary outcomes included treatment received and 2-year survival. A logit model estimated the effects of PET on diagnosis of locally advanced disease. Kaplan-Meier estimates described overall survival differences between PET and non-PET. Cox regression evaluated the association of PET on survival in patients with locally advanced disease. RESULTS: An association between PET and locally advanced disease was found (odds ratio, 2.86 [95% CI, 1.90-4.29) (P < .001). Two-year overall survival for patients with locally advanced disease with and without PET was 52% and 32%, respectively (P = .004), but there was no difference for all stages (P = .69). On Cox proportional hazard regression, PET had no association with survival in patients with locally advanced disease (hazard ratio, 1.208 [95% CI, 0.778-1.877]) (P = .40). CONCLUSIONS AND RELEVANCE: The increasing use of PET among patients with HNC is associated with a greater number of patients with higher-stage disease and a dilution of the population with higher-stage disease with patients who have a better prognosis. Thus, the improved survival in patients with locally advanced disease likely reflects selection bias and stage migration. Further research on PET use among patients with HNC is necessary to determine if it results in improved treatment for individual patients

Hymyc1 Downregulation Promotes Stem Cell Proliferation in Hydra vulgaris

Hydra is a unique model for studying the mechanisms underlying stem cell biology. The activity of the three stem cell lineages structuring its body constantly replenishes mature cells lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. In vertebrates, one of many genes that participate in regulating stem cell homeostasis is the protooncogene c-myc, which has been recently identified also in Hydra, and found expressed in the interstitial stem cell lineage. In the present paper, by developing a novel strategy of RNA interference-mediated gene silencing (RNAi) based on an enhanced uptake of small interfering RNAi (siRNA), we provide molecular and biological evidence for an unexpected function of the Hydra myc gene (Hymyc1) in the homeostasis of the interstitial stem cell lineage. We found that Hymyc1 inhibition impairs the balance between stem cell self renewal/differentiation, as shown by the accumulation of stem cell intermediate and terminal differentiation products in genetically interfered animals. The identical phenotype induced by the 10058-F4 inhibitor, a disruptor of c-Myc/Max dimerization, demonstrates the specificity of the RNAi approach. We show the kinetic and the reversible feature of Hymyc1 RNAi, together with the effects displayed on regenerating animals. Our results show the involvement of Hymyc1 in the control of interstitial stem cell dynamics, provide new clues to decipher the molecular control of the cell and tissue plasticity in Hydra, and also provide further insights into the complex myc network in higher organisms. The ability of Hydra cells to uptake double stranded RNA and to trigger a RNAi response lays the foundations of a comprehensive analysis of the RNAi response in Hydra allowing us to track back in the evolution and the origin of this process

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.</p> <p>Methods</p> <p>55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.</p> <p>Results</p> <p>Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.</p> <p>Conclusions</p> <p>Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.</p

Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy

BACKGROUND: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. METHODS: In the treatment plans, each patient’s heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. RESULTS: The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. CONCLUSIONS: We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions

State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

A dp53-Dependent Mechanism Involved in Coordinating Tissue Growth in Drosophila

A study in the Drosophila wing suggests a crucial role of p53 in the coordination of growth between adjacent cell populations to maintain organ proportions and shape