A six-parameter space to describe galaxy diversification

Galaxy diversification proceeds by transforming events like accretion, interaction or mergers. These explain the formation and evolution of galaxies that can now be described with many observables. Multivariate analyses are the obvious tools to tackle the datasets and understand the differences between different kinds of objects. However, depending on the method used, redundancies, incompatibilities or subjective choices of the parameters can void the usefulness of such analyses. The behaviour of the available parameters should be analysed before an objective reduction of dimensionality and subsequent clustering analyses can be undertaken, especially in an evolutionary context. We study a sample of 424 early-type galaxies described by 25 parameters, ten of which are Lick indices, to identify the most structuring parameters and determine an evolutionary classification of these objects. Four independent statistical methods are used to investigate the discriminant properties of the observables and the partitioning of the 424 galaxies: Principal Component Analysis, K-means cluster analysis, Minimum Contradiction Analysis and Cladistics. (abridged)Comment: Accepted for publicationin A\&

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

Exploiting biological and physical determinants of radiotherapy toxicity to individualise treatment.

This is the final version of the article. It first appeared from the British Institute of Radiology via http://dx.doi.org/10.1259/bjr.20150172The recent advances in radiation delivery can improve tumour control probability and reduce treatment related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day-to-day. Daily image guidance scans can be used to identify the position of normal tissue structures, and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues which limits radiotherapy dose and therefore tumour control. However, the dose response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of radiotherapy. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be due to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In prostate cancer patients receiving curative radiotherapy, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses (EUDs) was -2.7 Gy (5%), and a dose reduction was seen in 7/10 cases. If dose escalation were performed to take rectal dose back to the planned level, this should increase the mean tumour control probability (TCP) (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical radiotherapy who might benefit from either dose escalation, suggesting improved tumour cure, or reduced toxicity, or both.JS is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is supported by the NIHR Cambridge Biomedical Research Centre. The VoxTox Research Programme is funded by Cancer Research UK

Prophylactic radiotherapy against heterotopic ossification following internal fixation of acetabular fractures: a comparative estimate of risk.

OBJECTIVE: Radiotherapy (RT) is effective in preventing heterotopic ossification (HO) around acetabular fractures requiring surgical reconstruction. We audited outcomes and estimated risks from RT prophylaxis, and alternatives of indometacin or no prophylaxis. METHODS: 34 patients underwent reconstruction of acetabular fractures through a posterior approach, followed by a 8-Gy single fraction. The mean age was 44 years. The mean time from surgery to RT was 1.1 days. The major RT risk is radiation-induced fatal cancer. The International Commission on Radiological Protection (ICRP) method was used to estimate risk, and compared with a method (Trott and Kemprad) specifically for estimating RT risk for benign disease. These were compared with risks associated with indometacin and no prophylaxis. RESULTS: 28 patients (82%) developed no HO; 6 developed Brooker Class I; and none developed Class II-IV HO. The ICRP method suggests a risk of fatal cancer in the range of 1 in 1000 to 1 in 10,000; the Trott and Kemprad method suggests 1 in 3000. For younger patients, this may rise to 1 in 2000; and for elderly patients, it may fall to 1 in 6000. The risk of death from gastric bleeding or perforation from indometacin is 1 in 180 to 1 in 900 in older patients. Without prophylaxis risk of death from reoperation to remove HO is 1 in 4000 to 1 in 30,000. CONCLUSION: These results are encouraging, consistent with much larger series and endorse our multidisciplinary management. Risk estimates can be used in discussion with patients. ADVANCES IN KNOWLEDGE: The risk from RT prophylaxis is small, it is safer than indometacin and substantially overlaps with the range for no prophylaxis.NGB is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. JES is supported by Cancer Research UK through the Cambridge Cancer Centre.This is the accepted manuscript version. The final version is available from the BIR at http://www.birpublications.org/doi/abs/10.1259/bjr.20140398?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&

Random variation in rectal position during radiotherapy for prostate cancer is two to three times greater than that predicted from prostate motion.

OBJECTIVE: Radiotherapy for prostate cancer does not explicitly take into account daily variation in the position of the rectum. It is important to accurately assess accumulated dose (DA) to the rectum in order to understand the relationship between dose and toxicity. The primary objective of this work was to quantify systematic (Σ) and random (σ) variation in the position of the rectum during a course of prostate radiotherapy. METHODS: The rectum was manually outlined on the kilo-voltage planning scan and 37 daily mega-voltage image guidance scans for 10 participants recruited to the VoxTox study. The femoral heads were used to produce a fixed point to which all rectal contours were referenced. RESULTS: Σ [standard deviation (SD) of means] between planning and treatment was 4.2 mm in the anteroposterior (AP) direction and 1.3 mm left-right (LR). σ (root mean square of SDs) was 5.2 mm AP and 2.7 mm LR. Superior-inferior variation was less than one slice above and below the planning position. CONCLUSION: Our results for Σ are in line with published data for prostate motion. σ, however, was approximately twice as great as that seen for prostate motion. This suggests that DA may differ from planned dose in some patients treated with radiotherapy for prostate cancer. ADVANCES IN KNOWLEDGE: This work is the first to use daily imaging to quantify Σ and σ of the rectum in prostate cancer. σ was found to be greater than published data, providing strong rationale for further investigation of individual DA.JS is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is supported by the NIHR Cambridge Biomedical Research Centre. VoxTox is funded by Cancer Research UK.This is the final published version. It was first available from the British Institute of Radiology at http://dx.doi.org/10.1259/bjr.2014034