Herschel studies of core collapse supernova remnants at infrared wavelengths

Core collapse supernovae play a vital role in the evolution of the universe. They a major producers of metals and the only place where elements heavier than iron can be made. These metals can then combine to form molecules and dust, enriching the interstellar medium to provide cooling to form new stars. These molecules and dust, as well as metal cooling lines can all be observed in the infrared, making it a very interesting wavelength range in which to study supernovae and their remnants. This investigation of supernova remnants in the infrared has been made possible by the European Space Agency’s Herschel Space Observatory. Herschel studied the universe between 60 and 670 µm, covering the peak of dust emission, a large range of atomic fine structure cooling lines, a large portion of the carbon monoxide rotation ladder and other more exotic molecular line transitions. This thesis presents spectroscopic observations of the Cassiopeia A and Crab supernova remnants using two of the Herschel instruments to investigate their structure, physics and chemistry. It also presents the results of radiative transfer models based on photometric Herschel data to investigate more physical measurements of the mass of dust in supernova remnants. These models, along with others are then used to investigate the nature of dust formation in supernovae and the composition of this dust. Observations of the Crab Nebula with Herschel SPIRE made the first ever detection of a molecule containing a noble gas in space. Within the dense filaments of the nebula, two rotational lines of 36ArH+ were observed. This discovery was followed up with the VLT to try to find vibrational lines in the near infrared as well as an investigation of the potential presence of HeH+. Unfortunately these were unsuccessful. PACS and LWS observations were used to diagnose the conditions in the remnant, density, oxygen to nitrogen ratio and the ionic abundances of Nitrogen. Velocity information was also investigated and emitting regions compared to optical emission. Cassiopeia A was observed with Herschel PACS-IFU and SPIRE-FTS spectrometers. The PACS observations were used to look at the structure of the bright ring of the remnant. The 63 µm [O i] detected line emission along with upper limits on 146 µm [O i] emission were used to diagnose the temperature in the remnant assuming neutral hydrogen as a collision partner, found to be within a range of 100-1000K . Along with the SPIRE-FTS observations they were also used to investigate the formation of CO in the remnant. These CO observations were also used to diagnose conditions in the remnant. The temperature determined from CO in the neutral regions of the remnant was 300-500 K which is in agreement with the temperatures determined using the [O i] line ratios. By using photoionisation models of the Crab Nebula we were able to determine the mass of dust in the remnant. This modelling takes into account realistic heating of the dust, density distribution of the dust, the gas in the nebula and the size and species of the dust grains. We found that the dust mass is larger when these physical conditions are taken in to account. With our favoured geometry, distribution and grain species optical constants, we find a mass of 0.18 ± 0.03 M of dust, as opposed to the 0.1 M determined empirically, and a gas mass of 7.0 ± 0.5 M for the remnant

Fitness outcomes from a randomised controlled trial of exercise training for men with prostate cancer: the ENGAGE study

Purpose The main purpose of this study was to investigate the effects of a 12-week, clinician-referred, community-based exercise training program with supervised and unsupervised sessions for men with prostate cancer. The secondary purpose was to determine whether androgen deprivation therapy (ADT) modified responses to exercise training.Methods Secondary analysis was undertaken on data from a multicentre cluster randomised controlled trial in which 15 clinicians were randomly assigned to refer eligible patients to an exercise training intervention (n = 8) or to provide usual care (n = 7). Data from 119 patients (intervention n = 53, control n = 66) were available for this analysis. Outcome measures included fitness and physical function, anthropometrics, resting heart rate, and blood pressure.Results Compared to the control condition, men in the intervention significantly improved their 6-min walk distance (Mdiff = 49.98 m, padj = 0.001), leg strength (Mdiff = 21.82 kg, padj = 0.001), chest strength (Mdiff = 6.91 kg, padj = 0.001), 30-s sit-to-stand result (Mdiff = 3.38 reps, padj = 0.001), and reach distance (Mdiff = 4.8 cm, padj = 0.024). A significant difference (unadjusted for multiplicity) in favour of men in the intervention was also found for resting heart rate (Mdiff = −3.76 beats/min, p = 0.034). ADT did not modify responses to exercise training.Conclusions Men with prostate cancer who act upon clinician referrals to community-based exercise training programs can improve their strength, physical functioning, and, potentially, cardiovascular health, irrespective of whether or not they are treated with ADT.Implications for Cancer Survivors Clinicians should inform men with prostate cancer about the benefits of exercise and refer them to appropriately qualified exercise practitioners and suitable community-based programs

Protein kinase C epsilon is required for macrophage activation and defense against bacterial infection

Imperial Cancer Research Fund, and grants FEDER 2FD-1997-1432 from Comisión Interministerial de Ciencia y Tecnología (CICYT) and PM98-0120 from Dirección General de Enseñanza Superior e Investigación Científica, Spain. F. Otto was supported by Deutsche Forschungsgemeinschaft grant Ot 134/1-1

Online Assessment of Applied Anatomy Knowledge: The Effect of Images on Medical Students' Performance

Anatomical examinations have been designed to assess topographical and/or applied knowledge of anatomy with or without the inclusion of visual resources such as cadaveric specimens or images, radiological images, and/or clinical photographs. Multimedia learning theories have advanced the understanding of how words and images are processed during learning. However, the evidence of the impact of including anatomical and radiological images within written assessments is sparse. This study investigates the impact of including images within clinically oriented single‐best‐answer questions on students' scores in a tailored online tool. Second‐year medical students (n = 174) from six schools in the United Kingdom participated voluntarily in the examination, and 55 students provided free‐text comments which were thematically analyzed. All questions were categorized as to whether their stimulus format was purely textual or included an associated image. The type (anatomical and radiological image) and deep structure of images (question referring to a bone or soft tissue on the image) were taken into consideration. Students scored significantly better on questions with images compared to questions without images (P < 0.001), and on questions referring to bones than to soft tissue (P < 0.001), but no difference was found in their performance on anatomical and radiological image questions. The coding highlighted areas of “test applicability” and “challenges faced by the students.” In conclusion, images are critical in medical practice for investigating a patient's anatomy, and this study sets out a way to understand the effects of images on students' performance and their views in commonly employed written assessments

Predictors of adherence to a 12-week exercise program among men treated for prostate cancer: ENGAGE study

Understanding the factors that influence adherence to exercise programs is necessary to develop effective interventions for people with cancer. We examined the predictors of adherence to a supervised exercise program for participants in the ENGAGE study – a cluster randomized controlled trial that assessed the efficacy of a clinician-referred 12-week exercise program among men treated for prostate cancer. Demographic, clinical, behavioral, and psychosocial data from 52 participants in the intervention group were collected at baseline through self-report and medical records. Adherence to the supervised exercise program was assessed through objective attendance records. Adherence to the supervised exercise program was 80.3%. In the univariate analyses, cancer-specific quality of life subscales (role functioning r = 0.37, P = 0.01; sexual activity r = 0.26, P = 0.06; fatigue r = −0.26, P = 0.06, and hormonal symptoms r = −0.31, P = 0.03) and education (d = −0.60, P = 0.011) were associated with adherence. In the subsequent multivariate analysis, role functioning (B = 0.309, P = 0.019) and hormonal symptoms (B = −0.483, P = 0.054) independently predicted adherence. Men who experienced more severe hormonal symptoms had lower levels of adherence to the exercise program. Those who experienced more positive perceptions of their ability to perform daily tasks and leisure activities had higher levels of adherence to the exercise program. Hormonal symptoms and role functioning need to be considered when conducting exercise programs for men who have been treated for prostate cancer

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

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&

111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells

Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. This work demonstrates nanoparticle co-delivery of a therapeutic radionuclide plus a ruthenium-based radiosensitizer can achieve combinational and targeted therapeutic effects in cancer cells that overexpress EGFR

Domains of chronic low back pain and assessing treatment effectiveness : a clinical perspective

Nonspecific chronic low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment; however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioral therapy, acupuncture, and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this article is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living, and body composition), psychological (kinesiophobia, fear-avoidance, pain catastrophizing, pain self-efficacy, depression, anxiety, and sleep quality), social (social functioning and work absenteeism), and health-related quality-of-life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered "real" in an individual patient. This information can guide treatment selection when working with an individual with CLBP

Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition.

OBJECTIVE: The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. METHODS: A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. RESULTS: Venular tortuosity and diameter increased by approximately 2% (P < 10-300 ) and 0.6 μm (P < 10-6 ), respectively, per SD increase in BMI, waist circumference index, waist-hip ratio, total body fat mass index, and fat-free mass index (FFMI). Venular associations with adiposity persisted after adjustment for FFMI, whereas associations with FFMI were weakened by FMI adjustment. Arteriolar diameter (not tortuosity) narrowing with FFMI was independent of adiposity (-0.6 μm; -0.7 to -0.4 μm per SD increment of FFMI), while adiposity associations with arteriolar diameter were largely nonsignificant after adjustment for FFMI. CONCLUSIONS: This demonstrates, on an unprecedented scale, that venular tortuosity and diameter are more strongly associated with adiposity, whereas arteriolar diameter relates more strongly to fat-free mass. Different attributes of the retinal microvasculature may reflect distinct roles of body composition and fatness on the cardiometabolic system