Augmenting cancer registry data with health survey data with no cases in common : the relationship between pre-diagnosis health behaviour and post-diagnosis survival in oesophageal cancer

Background: For epidemiological research, cancer registry datasets often need to be augmented with additional data. Data linkage is not feasible when there are no cases in common between data sets. We present a novel approach to augmenting cancer registry data by imputing pre-diagnosis health behaviour and estimating its relationship with post-diagnosis survival time. Methods: Six measures of pre-diagnosis health behaviours (focussing on tobacco smoking, ‘at risk’ alcohol consumption, overweight and exercise) were imputed for 28,000 cancer registry data records of US oesophageal cancers using cold deck imputation from an unrelated health behaviour dataset. Each data point was imputed twice. This calibration allowed us to estimate the misclassification rate. We applied statistical correction for the misclassification to estimate the relative risk of dying within 1 year of diagnosis for each of the imputed behaviour variables. Subgroup analyses were conducted for adenocarcinoma and squamous cell carcinoma separately. Results: Simulated survival data confirmed that accurate estimates of true relative risks could be retrieved for health behaviours with greater than 5% prevalence, although confidence intervals were wide. Applied to real datasets, the estimated relative risks were largely consistent with current knowledge. For example, tobacco smoking status 5 years prior to diagnosis was associated with an increased age-adjusted risk of all cause death within 1 year of diagnosis for oesophageal squamous cell carcinoma (RR = 1.99 95% CI 1.24,3.12) but not oesophageal adenocarcinoma RR = 1.61, 95% CI 0.79,2.57). Conclusions: We have demonstrated a novel imputation-based algorithm for augmenting cancer registry data for epidemiological research which can be used when there are no cases in common between data sets. The algorithm allows investigation of research questions which could not be addressed through direct data linkage

Governance challenges of marine renewable energy developments in the US- creating the enabling conditions for successful project development

Increasingly, marine renewable energy developments are viewed as an opportunity to meet climate change obligations, with the added benefit of powering the economy and the creation of jobs. Technical, economic and engineering challenges co-exist with governance challenges in the development of large-scale marine renewable energy projects. This paper addresses the question, if the prerequisites for sustainable project development are evident in selected case studies. It also asks what lessons can be learned from current practice in the context of energy governance at the local level. The authors argue that these lessons can be central enablers to support decision makers in future programmes, to better understand how to build the enabling conditions for programme implementation towards renewable energy at higher spatial scales of governance, importantly the national level. The study builds on a multiple stakeholder approach involving interviews and group discussions with key individuals from industry, government and civil society in emerging pilot programmes along the East Coast of the United States (U.S.). New policy windows were opening at the time of the analysis and ambitious development was underway by a range of actors who are driving progress in the sector and positioning the area to become a major provider of blue energy

The effects of power plant passage on zooplankton mortalities: Eight years of study at the Donald C. Cook nuclear plant

Zooplankton mortalities resulting from passage through the Donald C. Cook Nuclear Plant (southeastern Lake Michigan) were studied over an 8-year (1975-1982) period. The power plant operated at a low [Delta]T (Diaptomus spp, Eurytemora affinis and Limnocalanus macrurus) were most sensitive to plant passage, cyclopoid copepods least sensitive, while cladocerans (Daphnia spp, Eubosmina coregoni) were intermediate in sensitivity. There was no relationship between zooplankton mortalities and temperature ([Delta]T, discharge water temperature), suggesting that thermal stresses were not the major source of mortality. The single exception was September 1978 when discharge water temperatures exceeded 35[deg]C and there were large differences between intake and discharge water zooplankton mortalities (net mortality differences of 14-22% for the two units). Mechanical stresses appeared to be the major cause of zooplankton mortality. However, there was only a weak relationship between mortality as a result of plant passage and zooplankton size. Based on our long-term preoperational (1970-1974) and operational (1975-1982) ecological studies in the vicinity of the power plant, we hypothesize that fish predation, rather than power plant operation, probably was the major source of zooplankton mortality in inshore waters during much of the year.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26160/1/0000237.pd

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Recent advances in thefield of immuno-oncology have brought transformative changes in the management ofcancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis andtreatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged aspotent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, therebyexpanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing thephenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinicallyrelevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential toguide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can nowprovide unprecedented insights into the tumour microenvironment, including the potential interplay betweenvarious cell types. However, there are significant challenges to widespread integration of these technologies in dailyresearch and clinical practice. This review addresses the challenges and potential solutions within a structuredframework of action from a regulatory and clinical trial perspective. New developments within thefield ofimmunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described,with a specific focus on translational implications across different subtypes of cancer

HerMES: A Statistical Measurement of the Redshift Distribution of Herschel-SPIRE Sources Using the Cross-correlation Technique

The wide-area imaging surveys with the Herschel Space Observatory at submillimeter (sub-mm) wavelengths have now resulted in catalogs of the order of one-hundred-thousand dusty, starburst galaxies. These galaxies capture an important phase of galaxy formation and evolution, but, unfortunately, the redshift distribution of these galaxies, N(z), is still mostly uncertain due to limitations associated with counterpart identification at optical wavelengths and spectroscopic follow-up. We make a statistical estimate of N(z) using a clustering analysis of sub-mm galaxies detected at each of 250, 350 and 500 μm from the Herschel Multi-tiered Extragalactic Survey centered on the Boötes field. We cross-correlate Herschel galaxies against galaxy samples at optical and near-IR wavelengths from the Sloan Digital Sky Survey, the NOAO Deep Wide Field Survey, and the Spitzer Deep Wide Field Survey. We create optical and near-IR galaxy samples based on their photometric or spectroscopic redshift distributions and test the accuracy of those redshift distributions with similar galaxy samples defined with catalogs from the Cosmological Evolution Survey (COSMOS), which has superior spectroscopic coverage. We model the clustering auto- and cross-correlations of Herschel and optical/IR galaxy samples to estimate N(z) and clustering bias factors. The S_(350) > 20 mJy galaxies have a bias factor varying with redshift as b(z) = 1.0^(+1.0)_(–0.5)(1 + z)^1.2^(+0.3)_(–0.7). This bias and the redshift dependence is broadly in agreement with galaxies that occupy dark matter halos of mass in the range of 1012 to 10^(13) M_☉. We find that galaxy selections in all three Spectral and Photometric Imaging Receiver (SPIRE) bands share a similar average redshift, with = 1.8 ± 0.2 for 250 μm selected samples, and = 1.9 ± 0.2 for both 350 and 500 μm samples, while their distributions behave differently. For 250 μm selected galaxies we find the a larger number of sources with z ≤ 1 when compared with the subsequent two SPIRE bands, with 350 and 500 μm selected SPIRE samples having peaks in N(z) at progressively higher redshifts. We compare our clustering-based N(z) results to sub-mm galaxy model predictions in the literature, and with an estimate of N(z) using a stacking analysis of COSMOS 24 μm detections

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the international immuno-oncology biomarker working group on breast cancer.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer

Commissioning measurements on an Elekta Unity MR-Linac

Magnetic resonance-guided radiotherapy technology is relatively new and commissioning publications, quality assurance (QA) protocols and commercial products are limited. This work provides guidance for implementation measurements that may be performed on the Elekta Unity MR-Linac (Elekta, Stockholm, Sweden). Adaptations of vendor supplied phantoms facilitated determination of gantry angle accuracy and linac isocentre, whereas in-house developed phantoms were used for end-to-end testing and anterior coil attenuation measurements. Third-party devices were used for measuring beam quality, reference dosimetry and during treatment plan commissioning; however, due to several challenges, variations on standard techniques were required. Gantry angle accuracy was within 0.1°, confirmed with pixel intensity profiles, and MV isocentre diameter was < 0.5 mm. Anterior coil attenuation was approximately 0.6%. Beam quality as determined by TPR20,10 was 0.705 ± 0.001, in agreement with treatment planning system (TPS) calculations, and gamma comparison against the TPS for a 22.0 × 22.0 cm2 field was above 95.0% (2.0%, 2.0 mm). Machine output was 1.000 ± 0.002 Gy per 100 MU, depth 5.0 cm. During treatment plan commissioning, sub-standard results indicated issues with machine behaviour. Once rectified, gamma comparisons were above 95.0% (2.0%, 2.0 mm). Centres which may not have access to specialized equipment can use in-house developed phantoms, or adapt those supplied by the vendor, to perform commissioning work and confirm operation of the MRL within published tolerances. The plan QA techniques used in this work can highlight issues with machine behaviour when appropriate gamma criteria are set

Submillimetre line spectrum of the Seyfert galaxy NGC1068 from the Herschel-SPIRE Fourier Transform Spectrometer

The first complete submillimetre spectrum (190-670um) of the Seyfert 2 galaxy NGC1068 has been observed with the SPIRE Fourier Transform Spectrometer onboard the {\it Herschel} Space Observatory. The sequence of CO lines (Jup=4-13), lines from water, the fundamental rotational transition of HF, two o-H_2O+ lines and one line each from CH+ and OH+ have been detected, together with the two [CI] lines and the [NII]205um line. The observations in both single pointing mode with sparse image sampling and in mapping mode with full image sampling allow us to disentangle two molecular emission components, one due to the compact circum-nuclear disk (CND) and one from the extended region encompassing the star forming ring (SF-ring). Radiative transfer models show that the two CO components are characterized by density of n(H_2)=10^4.5 and 10^2.9 cm^-3 and temperature of T=100K and 127K, respectively. The comparison of the CO line intensities with photodissociation region (PDR) and X-ray dominated region (XDR) models, together with other observational constraints, such as the observed CO surface brightness and the radiation field, indicate that the best explanation for the CO excitation of the CND is an XDR with density of n(H_2) 10^4 cm^-3 and X-ray flux of 9 erg s^-1 cm^-2, consistent with illumination by the active galactic nucleus, while the CO lines in the SF-ring are better modeled by a PDR. The detected water transitions, together with those observed with the \her \sim PACS Spectrometer, can be modeled by an LVG model with low temperature (T_kin \sim 40K) and high density (n(H_2) in the range 10^6.7-10^7.9 cm^-3).Comment: Accepted for publication on the Astrophysical Journal, 30 August 201

HerMES: point source catalogues from Herschel-SPIRE observations II

Key Programme on the Herschel Space Observatory. With a wedding cake survey strategy, it consists of nested fields with varying depth and area totalling ∼380 deg2. In this paper, we present deep point source catalogues extracted from Herschel-Spectral and Photometric Imaging Receiver (SPIRE) observations of all HerMES fields, except for the later addition of the 270 deg2 HerMES Large-Mode Survey (HeLMS) field. These catalogues constitute the second Data Release (DR2) made in 2013 October. A sub-set of these catalogues, which consists of bright sources extracted from Herschel-SPIRE observations completed by 2010 May 1 (covering ∼74 deg2) were released earlier in the first extensive data release in 2012 March. Two different methods are used to generate the point source catalogues, the SUSSEXTRACTOR point source extractor used in two earlier data releases (EDR and EDR2) and a new source detection and photometry method. The latter combines an iterative source detection algorithm, STARFINDER, and a De-blended SPIRE Photometry algorithm. We use end-to-end Herschel-SPIRE simulations with realistic number counts and clustering properties to characterize basic properties of the point source catalogues, such as the completeness, reliability, photometric and positional accuracy. Over 500 000 catalogue entries in HerMES fields (except HeLMS) are released to the public through the HeDAM (Herschel Database in Marseille) website (http://hedam.lam.fr/HerMES)

Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue

BACKGROUND: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. METHODS: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. RESULTS: From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4-5 toxicities, and the incidence of grade 2-3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes. CONCLUSION: Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue