Successful Downstaging of High Rectal and Recto-Sigmoid Cancer by Neo-Adjuvant Chemo-Radiotherapy

© 2008 Libertas Academica Ltd. All rights reserved.Purpose: The benefit of neoadjuvant therapy for tumours above the peritoneal reflection is not clear. The purpose of this study is to demonstrate the feasibility and downstaging of treating locally advanced tumours from high rectum to distal sigmoid with preoperative chemoradiotherapy (CRT).Methods and Materials: Seventeen patients with high rectal, rectosigmoid or distal sigmoid tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI findings indicating T4 disease or threatened circumferential resection margin. All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned conformal RT, 45 Gy in 25 fractions, with a boost of 5.4–9 Gy in 3–5 fractions. Thirteen patients were treated with concomitant oral or intravenous Fluoropyrimidine chemotherapy.Results: Median follow-up was 37 months. Overall survival was 82.35% (95% Confidence Interval (CI) 54.7–93.9) and disease free survival 81.25% (95% CI 52.5–93.5). Only 1 patient suffered loco-regional relapse. Chemotherapy regimens were well tolerated, though some patients required dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage, i.e. ‘downstaged’. Six patients (35.3%) achieved complete pathological response. Clear margins were attained in all but 1 patient. Three patients were converted from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3 grade IV late toxicities (LENT-SOMA).Conclusions: Locally advanced high rectal and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable toxicity, impressive down-staging, and clear surgical margins

Inflating Fat Bubbles in Clusters of Galaxies by Wide Jets

We conduct two-dimensional hydrodynamical simulations of jets expanding in the intra-cluster medium (ICM). We find that for a fat, i.e. more or less spherical, bubble attached to the center to be formed the jet should have high momentum flux and a large opening angle. Typically, the half opening angle should be >50 degrees, and the large momentum flux requires a jet speed of \~10,000 km/sec. The inflation process involves vortices and local instabilities which mix some ICM with the hot bubble. These results predict that most of the gas inside the bubble has a temperature of 3x10^8<T<3x10^9 K, and that large quantities of the cooling gas in cooling flow clusters are expelled back to the intra-cluster medium, and heated up. The magnetic fields and relativistic electrons that produce the synchrotron radio emission might be formed in the shock wave of the jet.Comment: Submitted to ApJ Letter

3D Simulations of MHD Jet Propagation Through Uniform and Stratified External Environments

We present a set of high-resolution 3D MHD simulations of steady light, supersonic jets, exploring the influence of jet Mach number and the ambient medium on jet propagation and energy deposition over long distances. The results are compared to simple self-similar scaling relations for the morphological evolution of jet-driven structures and to previously published 2D simulations. For this study we simulated the propagation of light jets with internal Mach numbers 3 and 12 to lengths exceeding 100 initial jet radii in both uniform and stratified atmospheres. The propagating jets asymptotically deposit approximately half of their energy flux as thermal energy in the ambient atmosphere, almost independent of jet Mach number or the external density gradient. Nearly one-quarter of the jet total energy flux goes directly into dissipative heating of the ICM, supporting arguments for effective feedback from AGNs to cluster media. The remaining energy resides primarily in the jet and cocoon structures. Despite having different shock distributions and magnetic field features, global trends in energy flow are similar among the different models. As expected the jets advance more rapidly through stratified atmospheres than uniform environments. The asymptotic head velocity in King-type atmospheres shows little or no deceleration. This contrasts with jets in uniform media with heads that are slowed as they propagate. This suggests that the energy deposited by jets of a given length and power depends strongly on the structure of the ambient medium. While our low-Mach jets are more easily disrupted, their cocoons obey evolutionary scaling relations similar to the high-Mach jets.Comment: Accepted in ApJ, 32 pages, 18 figures, animations available from: http://www.msi.umn.edu/Projects/twj/newsite/projects/radiojets/movies

Time-dependent radio emission from evolving jets

We investigated the time-dependent radiative and dynamical properties of light supersonic jets launched into an external medium, using hydrodynamic simulations and numerical radiative transfer calculations. These involved various structural models for the ambient media, with density profiles appropriate for galactic and extragalactic systems. The radiative transfer formulation took full account of emission, absorption, re-emission, Faraday rotation and Faraday conversion explicitly. High time-resolution intensity maps were generated, frame-by-frame, to track the spatial hydrodynamical and radiative properties of the evolving jets. Intensity light curves were computed via integrating spatially over the emission maps. We apply the models to jets in active galactic nuclei (AGN). From the jet simulations and the time-dependent emission calculations we derived empirical relations for the emission intensity and size for jets at various evolutionary stages. The temporal properties of jet emission are not solely consequences of intrinsic variations in the hydrodynamics and thermal properties of the jet. They also depend on the interaction between the jet and the ambient medium. The interpretation of radio jet morphology therefore needs to take account of environmental factors. Our calculations have also shown that the environmental interactions can affect specific emitting features, such as internal shocks and hotspots. Quantification of the temporal evolution and spatial distribution of these bright features, together with the derived relations between jet size and emission, would enable us to set constraints on the hydrodynamics of AGN and the structure of the ambient medium.Comment: 16 pages, 18 figures, MNRAS in press

An argument for the use of Aristotelian method in bioethics

The main claim of this paper is that the method outlined and used in Aristotle's Ethics is an appropriate and credible one to use in bioethics. Here “appropriate” means that the method is capable of establishing claims and developing concepts in bioethics and “credible” that the method has some plausibility, it is not open to obvious and immediate objection. It begins by suggesting why this claim matters and then gives a brief outline of Aristotle's method. The main argument is made in three stages. First, it is argued that Aristotelian method is credible because it compares favourably with alternatives. In this section it is shown that Aristotelian method is not vulnerable to criticisms that are made both of methods that give a primary place to moral theory (such as utilitarianism) and those that eschew moral theory (such as casuistry and social science approaches). As such, it compares favourably with these other approaches that are vulnerable to at least some of these criticisms. Second, the appropriateness of Aristotelian method is indicated through outlining how it would deal with a particular case. Finally, it is argued that the success of Aristotle's philosophy is suggestive of both the credibility and appropriateness of his method.</p

Postural stability in older adults with a distal radial fracture

BACKGROUND: The physical risk factors leading to distal radial fractures are poorly understood. The goal of this study was to compare postural stability between older adults with and without a prior distal radial fragility fracture. METHODS: This case-control evaluation was performed at a single tertiary institution. The fracture cohort comprised 23 patients treated for a low-energy distal radial fracture within 6 to 24 months prior to this study. Twenty-three age and sex-matched control participants, without a prior fragility fracture, were selected from an outpatient clinic population. All participants completed a balance assessment with a computerized balance platform device. Dynamic motion analysis (DMA) scores ranging from 0 to 1,440 points are produced, with lower scores indicating better postural stability. Participants also completed validated questionnaires for general health quality (EuroQol-5D-3L [EQ-5D-3L]) and physical activity (Physical Activity Scale for the Elderly [PASE]) and comprehensive health and demographic information including treatment for compromised balance or osteoporosis. Statistical analysis compared data between cases and controls using either the Student t test or the Mann-Whitney U test. RESULTS: There were no significant differences (p > 0.05) in age, sex, body mass index, physical activity score, or EQ-5D-3L general health visual analog scale score between participants with or without prior distal radial fracture. The fracture cohort demonstrated poorer balance, with higher DMA scores at 933 points compared with 790 points for the control cohort (p = 0.008). Nineteen patients (83%) in the fracture cohort reported having dual x-ray absorptiometry (DXA) scans within 5 years prior to this study, but only 2 patients (9%) had ever been referred for balance training with physical therapy. CONCLUSIONS: Older adults who sustain low-energy distal radial fractures demonstrate impaired postural stability compared with individuals of a similar age who have not sustained such fractures. Following a distal radial fracture, these patients may benefit from interventions to improve postural stability. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence

Patterns of change and stability in caregiver burden and life satisfaction from 1 to 2 years after severe traumatic brain injury : a Norwegian longitudinal study

Objectives: To assess burden and life satisfaction in caregivers of patients with severe traumatic brain injury (sTBI) at 1 and 2 years post-injury, to examine if change in burden can be predicted by caregiver and patient demographics, patient’s functional status, caregiver’s social network or caregiver’s level of burden at 1 year. Design: Prospective national multicenter study. Self-report from caregivers, patient data collected from a national cohort study on patients with sTBI. Participants: 80 caregivers. Main outcome measure: The Caregiver Burden Scale (CBS), life satisfaction. Results: The total caregiver burden increased significantly between years 1 and 2 post-injury (p=0.04). Life Satisfaction was significantly lower at 2 years follow-up (p=0.03) than at 1 year. Thirty percent of the caregivers reported an increased burden, 55% were stable, and 15% had a decrease in burden between the two follow-up times. Logistic regression analyses revealed that experiencing loneliness was an independent predictor of increased burden from 1 to 2 years post-injury (OR=4.35, p<0.05). Conclusions: The results demonstrate a need for long-term follow-up of patients and caregivers that particularly focuses on professional support to relieve caregiver burden and risk of loneliness or social isolation. This group may benefit from additional follow-up interventions tailored to their needs

Positive selection inhibits gene mobilization and transfer in soil bacterial communities

Horizontal gene transfer (HGT) between bacterial lineages is a fundamental evolutionary process that accelerates adaptation. Sequence analyses show that conjugative plasmids are principal agents of HGT in natural communities. However, we lack understanding of how the ecology of bacterial communities and their environments affect the dynamics of plasmid-mediated gene mobilization and transfer. Here we show, in simple experimental soil bacterial communities containing a conjugative mercury resistance plasmid, the repeated, independent mobilization of transposon-borne genes from chromosome to plasmid, plasmid to chromosome and, in the absence of mercury selection, interspecific gene transfers from the chromosome of one species to the other via the plasmid. By reducing conjugation, positive selection for plasmid-encoded traits, like mercury resistance, can consequently inhibit HGT. Our results suggest that interspecific plasmid-mediated gene mobilization is most likely to occur in environments where plasmids are infectious, parasitic elements rather than those where plasmids are positively selected, beneficial elements