Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region.

BACKGROUND: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast-enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. PURPOSE: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. STUDY TYPE: Animal model. SUBJECTS: Mice bearing orthotopic glioblastoma xenografts generated from a patient-derived glioblastoma cell line. FIELD STRENGTH/SEQUENCES: 7T perfusion images acquired using a high signal-to-noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1 /T2 weighted, contrast-enhanced T1 , diffusion-weighted, and apparent diffusion coefficient). ASSESSMENT: Immunohistochemistry sections were stained for human leukocyte antigen (probing human-derived tumor cells). To achieve quantitative MRI-tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a "ground truth." STATISTICAL TESTS: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two-tailed, paired t-test used for statistical analysis. RESULTS: High comparison test results (Dice 0.62-0.72, Accuracy 0.86-0.88, Sensitivity 0.51-0.7, and Specificity 0.92-0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51-0.61). MRI/histology voxel-to-voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). DATA CONCLUSION: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy. LEVEL OF EVIDENCE: 1 Technical stage: 2 J. Magn. Reson. Imaging 2019;50:529-540.

First Demonstration of Electrostatic Damping of Parametric Instability at Advanced LIGO.

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude.

Core-shell formation in self-induced InAlN nanorods.

We have examined the early stages of self-induced InAlN core-shell nanorod (NR) formation processes on amorphous carbon substrates in plan-view geometry by means of transmission electron microscopy methods. The results show that the grown structure phase separates during the initial moments of deposition into a majority of Al-rich InAlN and a minority of In-enriched InAlN islands. The islands possess polygonal shapes and are mainly oriented along a crystallographic c-axis. The growth proceeds with densification and coalescence of the In-enriched islands, resulting in a base for the In-enriched NR cores with shape transformation to hexagonal. The Al-rich shell formation around such early cores is observed at this stage. The matured core-shell structure grows axially and radially, eventually reaching a steady growth state which is dominated by the axial NR growth. We discuss the NR formation mechanism by considering the adatom surface kinetics, island surface energy, phase separation of InAlN alloys, and incoming flux directions during dual magnetron sputter epitaxy.

Effects of configurational disorder on the elastic properties of icosahedral boron-rich alloys based on B6O, B13C2, and B4C, and their mixing thermodynamics.

The elastic properties of alloys between boron suboxide (B6O) and boron carbide (B13C2), denoted by (B6O)(1-x)(B13C2)(x), as well as boron carbide with variable carbon content, ranging from B13C2 to B4C are calculated from first-principles. Furthermore, the mixing thermodynamics of (B6O)(1-x)(B13C2)(x) is studied. A superatom-special quasirandom structure approach is used for modeling different atomic configurations, in which effects of configurational disorder between the carbide and suboxide structural units, as well as between boron and carbon atoms within the units, are taken into account. Elastic properties calculations demonstrate that configurational disorder in B13C2, where a part of the C atoms in the CBC chains substitute for B atoms in the B12 icosahedra, drastically increase the Young's and shear modulus, as compared to an atomically ordered state, B12(CBC). These calculated elastic moduli of the disordered state are in excellent agreement with experiments. Configurational disorder between boron and carbon can also explain the experimentally observed almost constant elastic moduli of boron carbide as the carbon content is changed from B4C to B13C2. The elastic moduli of the (B6O)(1-x)(B13C2)(x) system are also practically unchanged with composition if boron-carbon disorder is taken into account. By investigating the mixing thermodynamics of the alloys, in which the Gibbs free energy is determined within the mean-field approximation for the configurational entropy, we outline the pseudo-binary phase diagram of (B6O)(1-x)(B13C2)(x). The phase diagram reveals the existence of a miscibility gap at all temperatures up to the melting point. Also, the coexistence of B6O-rich as well as ordered or disordered B13C2-rich domains in the material prepared through equilibrium routes is predicted.

Stacking fault related luminescence in GaN nanorods.

Optical and structural properties are presented for GaN nanorods (NRs) grown in the [0001] direction on Si(111) substrates by direct-current reactive magnetron sputter epitaxy. Transmission electron microscopy (TEM) reveals clusters of dense stacking faults (SFs) regularly distributed along the c-axis. A strong emission line at ∼3.42 eV associated with the basal-plane SFs has been observed in luminescence spectra. The optical signature of SFs is stable up to room temperatures with the activation energy of ∼20 meV. Temperature-dependent time-resolved photoluminescence properties suggest that the recombination mechanism of the 3.42 eV emission can be understood in terms of multiple quantum wells self-organized along the growth axis of NRs.

Simultaneous monitoring of faecal indicators and harmful algae using an in-situ autonomous sensor.

UNLABELLED: Faecal indicator bacteria (FIB) and harmful algal blooms (HABs) threaten the health and the economy of coastal communities worldwide. Emerging automated sampling technologies combined with molecular analytical techniques could enable rapid detection of micro-organisms in-situ, thereby improving resource management and public health decision-making. We evaluated this concept using a robotic device, the Environmental Sample Processor (ESP). The ESP automates in-situ sample collection, nucleic acid extraction and molecular analyses. Here, the ESP measured and reported concentrations of FIB (Enterococcus spp.), a microbial source-tracking marker (human-specific Bacteriodales) and a HAB species (Psuedo-nitzschia spp.) over a 45-day deployment on the Santa Cruz Municipal Wharf (Santa Cruz, CA, USA). Both FIB and HABs were enumerated from single in-situ collected water samples. The in-situ qPCR efficiencies ranged from 86% to 105%, while the limit of quantifications during the deployment was 10 copies reaction(-1) . No differences were observed in the concentrations of enterococci, the human-specific marker in Bacteroidales spp., and P. australis between in-situ collected sample and traditional hand sampling methods (P > 0·05). Analytical results were Internet-accessible within hours of sample collection, demonstrating the feasibility of same-day public notification of current water quality conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents the first report of in-situ qPCR enumeration of both faecal indicators and harmful algal species in coastal marine waters. We utilize a robotic device for in-situ quantification of enterococci, the human-specific marker in Bacteriodales and Pseudo-nitzschia spp. from the same water samples collected and processed in-situ. The results demonstrate that rapid, in-situ monitoring can be utilized to identify and quantify multiple health-relevant micro-organisms important in water quality monitoring and that this monitoring can be used to inform same-day notifications.

Insights into the pathophysiology of catch-up compared with non-catch-up growth in children born small for gestational age: an integrated analysis of metabolic and transcriptomic data.

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4-9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

Regional melanoma incidence in England, 1996-2006: reversal of north-south latitude trends among the young female population.

BACKGROUND: Melanoma incidence often shows an increasing latitudinal gradient from north to south among white European populations. OBJECTIVES: To assess emerging regional melanoma incidence patterns in England. METHODS: All primary invasive cutaneous melanomas diagnosed in England in people aged 10-89 years, in 1996-2006, were ascertained. Age-standardized incidence rates by sex, age and Government Office Region were calculated for the entire population and for the white population only. Rates according to socioeconomic deprivation were further calculated among those aged under 30 years. Regional heterogeneity and latitude and deprivation trends were assessed by Poisson regression and tests for trend. RESULTS: Overall, melanoma incidence in England was highest in the South West (overall, 18·75; white, 19·03 per 100,000) and lowest in London (overall, 8·85; white, 11·22 per 100,000). Incidence significantly increased with more southerly latitudes in all white adults aged over 30 years (P < 0·0001), except women aged 30-49 years (1·8%, P = 0·10). However, these north-south latitude trends were reversed in white 10-29 year olds, with sex-specific analyses showing an absence of trend in male subjects (2·7%, P = 0·41) and a strong decreasing trend (-9·8%, P < 0·0001) in female subjects. The highest rates in the young female population occurred in the North West (5·46 per 100,000), and specifically in the second most deprived (5·69 per 100,000) and the second most affluent (6·48 per 100,000) groups. CONCLUSIONS: Melanoma incidence is high in young people in northern England, including among the moderately deprived, reversing the expected north-south incidence gradients. Prevalent sunbed use in northern England and holiday sun exposure abroad may explain these emerging trends.

Evaluating potential of multi-parametric MRI using co-registered histology: Application to a mouse model of glioblastoma.

BACKGROUND: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast-enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. PURPOSE: MRI is capable of generating a range of image contrasts which are commonly assessed individually by qualitative visual inspection. It has long been hypothesized that better diagnoses could be achieved by combining these multiple images, so called multi-parametric or multi-spectral MRI. However, the lack of clinical histology and the difficulties of co-registration, has meant this hypothesis has never been rigorously tested. Here we test this hypothesis, using a previously published multi-dimensional dataset consisting of registered MR images and histology. STUDY TYPE: Animal Model. SUBJECTS: Mice bearing orthotopic glioblastoma xenografts generated from a patient-derived glioblastoma cell line. FIELD STRENGTH/SEQUENCES: 7 Tesla, T1/T2 weighted, T2 mapping, contrast enhance T1, diffusion-weighted, diffusion tensor imaging. ASSESSMENT: Immunohistochemistry sections were stained for Human Leukocyte Antigen (probing human-derived tumor cells). To achieve quantitative MRI-tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as 'ground truth'. STATISTICAL TESTS: Sensitivity, specificity, accuracy and Dice similarity indices were calculated. ANOVA, t-test, Bonferroni correction and Pearson coefficients were used for statistical analysis. RESULTS: Correlation coefficient analysis with co-registered 'ground truth' histology showed interactive regression maps had higher correlation coefficients and sensitivity values than T2W, ADC, FA, and T2map. Further, the interaction regression maps showed statistical improved detection of tumor volume. DATA CONCLUSION: Voxel-by-voxel analysis provided quantitative evidence confirming the hypothesis that mpMRI can, potentially, better distinguish between the tumor region and normal tissue.

Increasing rates of cervical cancer in young women in England: an analysis of national data 1982-2006.

BACKGROUND: In England, cervical cancer is the second most common cancer in women aged under 35 years. Overall incidence of cervical cancer has decreased since the introduction of the national screening programme in 1988 but recent trends of incidence in young women have not been studied in detail. METHODS: Information on 71,511 incident cases of cervical cancer in England, 1982-2006, in 20-79-year-olds was extracted from a national cancer registration database. Changes in incidence were analysed by age group, time period and birth cohort. Poisson regression was used to estimate annual percentage change (APC). RESULTS: Overall incidence, during 1982-2006, fell significantly from 213 to 112 per million person years. However, in 20-29-year-olds, after an initial fall, incidence increased significantly during 1992-2006, (APC 2.16). In 30-39-year-olds incidence stabilised during the latter part of the study period. The pattern was most marked in the North East, Yorkshire and the Humber and East Midlands regions. Birth cohorts that were initially called for screening between 60-64 and 35-39 years of age show an incidence peak soon after the age of presumed first screen, whereas younger birth cohorts show a peak at about 35 years of age. Incidence in the 1977-1981 birth cohort has increased relative to that among women born between 1962 and 1976. CONCLUSION: These results have implications for cervical screening, human papilloma virus vaccination and other public health interventions targeting young people.

Increases in invasive melanoma in England, 1979-2006, by anatomical site.

BACKGROUND: National melanoma incidence trends with details of anatomical site have not been previously described for England. OBJECTIVES: To describe site-specific trends in cutaneous melanoma for England as a whole during the last three decades. METHODS: Anonymized data, 1979-2006, were obtained from national cancer registrations of all patients in England up to age 89years with incident primary invasive cutaneous melanomas (n=124055). Sex-specific age-standardized incidence rates and average annual percentage change in rates were calculated for each broad anatomical site. RESULTS: Overall incidence rates of cutaneous melanoma in England, 1979-2006, were 81 and 100 per million, in males and females, respectively. Site-specific rates were consistently highest on the lower limbs in females followed by the trunk in males. Greatest annual increases occurred on the trunk in both sexes over 45years (males 9·9%, females 6·8%), then upper limbs (males 8·7%, females 6·8%). Incidence trends in males relative to females varied little across sites apart from a more rapid rise in head/neck melanomas in males than in females after the 1980s. CONCLUSIONS: Invasive melanoma rates continue to rise in England, particularly on the trunk and arms, and in males on the head/neck. The steeper increases in melanoma rates among males are consistent with their greater sun exposure and poorer compliance with sun protection measures than females.

Geographical and temporal distribution of cancer survival in teenagers and young adults in England.

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981-2002.

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.

Infectious exposure in the first year of life and risk of central nervous system tumors in children: analysis of day care, social contact, and overcrowding.

Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case-control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08-1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12-2.83). Those who had attended informal (OR 0.86, 95% CI 0.68-1.09) or formal day care (OR 0.93, 95% CI 0.68-1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation.

Large-scale cell culture in biotechnology.

The purpose of this article is to review the current state of large-scale cell culture in terms of its applications, problems, and potential. Because of the commercial and proprietary nature of most large-scale cell culture processes, this review does not contain many detailed scientific results although an attempt is made to address some key issues and findings. Much of this summary deals with processes having an established, commercial track record but some attention is given to more recent innovations with interesting potential applications. Reference is made to plant cell culture but the main emphasis is on mammalian cells.

Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.

Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation.

BACKGROUND: A variety of abnormalities have been demonstrated at chromosome 11p15 in individuals with overgrowth and growth retardation. The identification of these abnormalities is clinically important but often technically difficult. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a simple but effective technique able to identify and differentiate methylation and copy number abnormalities, and thus is potentially well suited to the analysis of 11p15. AIMS: To customize and test an MS-MLPA assay capable of detecting and distinguishing the full spectrum of known 11p15 epigenetic and copy number abnormalities associated with overgrowth and growth retardation and to assess its effectiveness as a first line investigation of these abnormalities. METHODS: Five synthetic probe pairs were designed to extend the range of abnormalities detectable with a commercially available MS-MLPA assay. To define the normal values, 75 normal control samples were analysed using the customized assay. The assay was then used to analyse a "test set" of 24 normal and 27 abnormal samples, with data analysed by two independent blinded observers. The status of all abnormal samples was confirmed by a second technique. RESULTS: The MS-MLPA assay gave reproducible, accurate methylation and copy number results in the 126 samples assayed. The blinded observers correctly identified and classified all 51 samples in the test set. CONCLUSIONS: MS-MLPA robustly and sensitively detects and distinguishes epigenetic and copy number abnormalities at 11p15 and is an effective first line investigation of 11p15 in individuals with overgrowth or growth retardation.

Comparison of Moseley and Rotterdam straight-line graphs in predicting leg lengths and leg-length discrepancy at maturity.

PURPOSE: One method of predicting leg-length discrepancy at maturity is the Moseley straight-line graph. Beumer et al developed an alternative graph, using a more modern Dutch population. The purpose of this study was to compare the prediction accuracy of these two graphs in a cohort of patients treated at our institution using epiphysiodesis. METHODS: We identified 76 patients treated using epiphysiodesis for leg-length discrepancy who were followed to maturity and had adequate preoperative radiographic assessment for straight-line graph construction. We compared predicted long leg length (after epiphysiodesis), short leg length, and residual leg-length discrepancy to actual outcome for both methods, using both chronological and skeletal ages. RESULTS: Both methods were more accurate using skeletal age rather than chronological age. The Rotterdam graph showed modest improved accuracy compared to the Moseley graph in developmental aetiologies and in Hispanic patients. Using a difference of one centimetre in prediction error as clinically relevant (long leg [after epiphysiodesis], short leg, and leg-length discrepancy in each of the 76 patients, 228 predictions), we found comparable predictions in 171, more accurate prediction using the Rotterdam in 32, and using the Moseley in 25 predictions. CONCLUSIONS: Straight-line graphs provide a generally more accurate prediction of leg lengths at maturity by virtue of multiple preoperative evaluations. The Rotterdam straight-line graph was equal to or superior to the Moseley graph in most patients in this cohort. Use of skeletal age resulted in more accurate predictions than chronological age. Clinicians should remain familiar with the concept and use of the straight-line graph. LEVEL OF EVIDENCE: III, case-control study.

Stacked in-plane histology for quantitative validation of non-invasive imaging biomarkers: Application to an infiltrative brain tumour model.

BACKGROUND: While it is generally agreed that histopathology is the gold standard for assessing non-invasive imaging biomarkers, most validation has been by qualitative visual comparison. To date, the difficulties involved in accurately co-registering histology sections with imaging slices have prevented a voxel-by-voxel assessment of imaging modalities. By contrast with previous studies, which focus on improving the registration algorithms, we have taken the approach of improving the quality of the histological processing and analysis. NEW METHOD: To account for imaging slice orientation and thickness, multiple histology sections were cut in the MR imaging plane and averaged to produce stacked in-plane histology (SIH) maps. When combined with intensity sensitive staining this approach gives histopathology maps, which can be used as the gold standard to validate imaging biomarkers. RESULTS: We applied this pipeline to a patient-derived mouse model of glioblastoma multiforme (GBM). Increasing the number of stacked histology sections significantly increased SIH measured tumour volume. The SIH technique proposed here resulted in reduced variability of volume measurements and this allowed significant improvements in the quantitative volumetric assessment of multiple MRI modalities. Further, high quality registration enabled a voxel-wise comparison between MRI and histopathology maps. Previous approaches to the validation of imaging biomarkers with histology, have been either qualitative or of limited accuracy. Here we propose a pipeline that allows for a more accurate validation via co-registration with SIH maps, potentially allowing validation in a voxel-wise mode. CONCLUSION: This work demonstrates that methodically produced SIH maps facilitate the quantitative histopathologic assessment of imaging biomarkers.

Survival from cancer in teenagers and young adults in England, 1979-2003.

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13-24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30,000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996-2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.