The Road Not Taken and Choices in Radiation Oncology

The authors look back at the five decades of radiation oncology and consider how one's choices and decisions influence how a career is pursued and how a professional life is lived

Why "Radiation Oncology"

Radiotherapy continues to be a major treatment for solid tumours and is a cornerstone of modern oncology. The term 'radiation oncology' describes the integration of radiation therapy into the complexity of multi-modal therapy. Over the last ten years the crucial role of radiation therapy as part of multi-modality protocols in cancer care has been documented in numerous Phase III trials. Advances in treatment technology as well as the underlying biology of tumour resistance mechanisms will further strengthen the role of radiation oncology. The scientific role of radiation oncology is reflected by the increase in the number of papers related to radiation oncology in resources like Medline. In order to reflect the growing scientific importance of radiation oncology, radiation physics and radiation biology, we have initiated Radiation Oncology as the first open access journal in the field. Open access allows for a rapid and transparent publication process together with an unequalled opportunity to reach the widest reader spectrum possible

Symmetries of Holographic Minimal Models

It was recently proposed that a large N limit of a family of minimal model CFTs is dual to a certain higher spin gravity theory in AdS_3, where the 't Hooft coupling constant of the CFT is related to a deformation parameter of the higher spin algebra. We identify the asymptotic symmetry algebra of the higher spin theory for generic 't Hooft parameter, and show that it coincides with a family of W-algebras previously discovered in the context of the KP hierarchy. We furthermore demonstrate that this family of W-algebras controls the representation theory of the minimal model CFTs in the 't Hooft limit. This provides a non-trivial consistency check of the proposal and explains part of the underlying mechanism.Comment: 25 pages; references added and minor corrections (published version

Discrete Information from CHL Black Holes

AdS_2/CFT_1 correspondence predicts that the logarithm of a Z_N twisted index over states carrying a fixed set of charges grows as 1/N times the entropy of the black hole carrying the same set of charges. In this paper we verify this explicitly by calculating the microscopic Z_N twisted index for a class of states in the CHL models. This demonstrates that black holes carry more information about the microstates than just the total degeneracy.Comment: LaTeX file, 24 pages; v2: references adde

Neural Correlates of Threat Perception: Neural Equivalence of Conspecific and Heterospecific Mobbing Calls Is Learned

Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise [1]–[2]. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators [3]. Mobbing calls produced in response to smaller, higher-threat predators contain more “D” notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators [4]. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned

A Twist in the Dyon Partition Function

In four dimensional string theories with N=4 and N=8 supersymmetries one can often define twisted index in a subspace of the moduli space which captures additional information on the partition function than the ones contained in the usual helicity trace index. We compute several such indices in type IIB string theory on K3 x T^2 and T^6, and find that they share many properties with the usual helicity trace index that captures the spectrum of quarter BPS states in N=4 supersymmetric string theories. In particular the partition function is a modular form of a subgroup of Sp(2,Z) and the jumps across the walls of marginal stability are controlled by the residues at the poles of the partition function. However for large charges the logarithm of this index grows as 1/n times the entropy of a black hole carrying the same charges where n is the order of the symmetry generator that is used to define the twisted index. We provide a macroscopic explanation of this phenomenon using quantum entropy function formalism. The leading saddle point corresponding to the attractor geometry fails to contribute to the twisted index, but a Z_n orbifold of the attractor geometry produces the desired contribution.Comment: LaTeX file, 35 pages; v2: references adde

Multimodal Management of Atrophic Acne Scarring in the Aging Face

Atrophic facial acne scarring is a widely prevalent condition that can have a negative impact on a patient’s quality of life. The appearance of these scars is often worsened by the normal effects of aging. A number of options are available for the treatment of acne scarring, including chemical peeling, dermabrasion, ablative or nonablative laser resurfacing, dermal fillers, and surgical techniques such as subcision or punch excision. Depending on the type and extent of scarring, a multimodal approach is generally necessary to provide satisfactory results. Resurfacing techniques correct surface irregularities, long-lasting dermal fillers address the volume loss resulting from acne, and sub-superficial musculoaponeurotic system (SMAS) face-lift procedures counter the soft tissue laxity and ptosis associated with aging. This article briefly reviews the evolution of individual approaches to treating atrophic acne scarring, followed by case examples illustrating results that can be achieved using a multimodal approach. Representative cases from patients in their 30s, 40s, and 50s are presented. In the author’s clinical practice, multimodal approaches incorporating fractionated laser, injectable poly-l-lactic acid, and sub-SMAS face-lift procedures have achieved optimal aesthetic outcomes, high patient satisfaction, and durability of aesthetic effect over time

Colorectal cancer screening using the faecal occult blood test (FOBt): a survey of GP attitudes and practices in the UK

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the third most common cancer in the UK. Five-year survival rates are less than 50%, largely because of late diagnosis. Screening using faecal occult blood tests (FOBt) can detect bowel cancer at an earlier stage than symptomatic presentation, and has the potential to significantly decrease colorectal cancer mortality. However, uptake of screening is currently low, despite the introduction of the NHS Bowel Cancer Screening Programme (NHSBCSP), and it has been suggested that GP recommendations of screening can improve patient compliance. GP recommendation of CRC screening is argued to be affected by attitudes towards it, along with perceptions of its efficacy.</p> <p>Methods</p> <p>This paper presents the findings of a cross-sectional postal survey of GPs in the UK which aimed to investigate GPs' attitudes in relation to colorectal cancer screening and the use of FOBt in routine practice. An 'attitude' score was calculated, and binary logistic regression used to evaluate the association of socio-demographic and general practice attributes with attitudes towards CRC screening and FOBt.</p> <p>Results</p> <p>Of 3,191 GPs surveyed, 960 returned usable responses (response rate 30.7%). Positive attitudes were associated with personal experience of CRC screening and Asian or Asian British ethnicity. GPs from practices located in more deprived locations were also more likely to have positive attitudes towards FOBt and its recommendation to patients.</p> <p>Conclusions</p> <p>The success of population-based screening for CRC will largely be determined by GP attitudes and support, particularly with regard to FOBt. Previous research has implied that South Asian GPs are more likely to have negative attitudes towards FOBt screening, however, our research suggests that this is not a group requiring targeted interventions to increase their support for the NHSBCSP. Of the available CRC screening tests, GPs perceived FOBt to be the most appropriate for population-based screening.</p

The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

<p>Abstract</p> <p>Background</p> <p>This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells.</p> <p>Methods</p> <p>The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions <it>in vitro</it>. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect.</p> <p>Results</p> <p>Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration.</p> <p>Conclusion</p> <p>Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner.</p

Association between tissue hypoxia and elevated non-protein sulphydryl concentrations in human cervical carcinoma xenografts

A double staining technique was developed for the simultaneous measurement of tissue hypoxia and the concentration of non-protein sulphydryls (NPSH), based on the fluorinated nitroimidazole EF5 and the fluorescent histochemical NPSH stain 1-(4-chloromercuriphenoylazo)-naphthol-2 (mercury orange). Cryostat sections of tumour tissue were examined by fluorescence image analysis, using a computer-controlled microscope stage to generate large tiled field images of the cut tumour surface. This method was applied to the human cervical squamous cell carcinoma lines ME180 and SiHa, grown as xenografts in severe combined immunodeficient (SCID) mice, in order to determine if there is a systematic relationship between tissue hypoxia and NPSH levels. Hypoxic regions of the tumours, defined by EF5 labelling, were found to show greater NPSH concentrations relative to better oxygenated regions. This is probably due to increases in glutathione, since the ME180 and SiHa xenografts contained low levels of cysteine and metallothionein; the other major cellular thiols that can bind to mercury orange. Because the effects of glutathione on radiation and chemotherapy resistance are likely to be greater under hypoxic conditions, these results have potentially important implications for the study of resistance mechanisms in solid tumours. © 1999 Cancer Research Campaig