Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials

Climate change and anthropogenic intervention impact on the hydrologic anomalies in a semi-arid area : lower Zab river basin, Iraq

Climate change impact, drought phenomena and anthropogenic stress are of increasing apprehension for water resource managers and strategists, particularly in arid regions. The current study proposes a generic methodology to evaluate the potential impact of such changes at a basin scale. The Lower Zab River Basin located in the north of Iraq has been selected for illustration purposes. The method has been developed through evaluating changes during normal hydrological years to separate the effects of climate change and estimate the hydrologic abnormalities utilising Indicators of Hydrologic Alteration. The meteorological parameters were perturbed by applying adequate delta perturbation climatic scenarios. Thereafter, a calibrated rainfall-runoff model was used for streamflow simulations. Findings proved that climate change has a more extensive impact on the hydrological characteristics of the streamflow than anthropogenic intervention (i.e. the construction of a large dam in the catchment). The isolated baseflow is more sensitive to the precipitation variations than to the variations of the potential evapotranspiration. The current hydrological anomalies are expected to continue. This comprehensive basin study demonstrates how climate change impact, anthropogenic intervention as well as hydro-climatic drought and hydrological anomalies can be evaluated with a new methodology

Improved model for human induced vibrations of high-frequency floors

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe key UK design guidelines published by the Concrete Society and Concrete Centre for single human walking excitation of high-frequency floors were introduced more than 10 years ago. The corresponding walking force model is derived using a set of single footfalls recorded on a force plate and it features a deterministic approach which contradicts the stochastic nature of human-induced loading, including intra- and inter- subject variability. This paper presents an improved version of this force model for high-frequency floors with statistically defined parameters derived using a comprehensive database of walking force time histories, comprising multiple successive footfalls that are continuously measured on an instrumented treadmill. The improved model enables probability-based prediction of vibration levels for any probability of non-exceedance, while the existing model allows for vibration prediction related to 75% probability of non-exceedance for design purposes. Moreover, the improved model shifts the suggested cut-off frequency between low- and high-frequency floors from 10 Hz to 14 Hz. This is to account for higher force harmonics that can still induce the resonant vibration response and to avoid possible significant amplification of the vibration response due to the near-resonance effect. Minor effects of near-resonance are taken into account by a damping factor. The performance of the existing and the improved models is compared against numerical simulations carried out using a finite element model of a structure and the treadmill forces. The results show that while the existing model tends to overestimate or underestimate the vibration levels depending on the pacing rate, the new model provides statistically reliable estimations of the vibration responses. Hence, it can be adopted in a new generation of the design guidelines featuring a probabilistic approach to vibration serviceability assessment of high-frequency floors.The authors would like to acknowledge the College of Engineering, Mathematics and Physical Sciences in the University of Exeter for the financial support provided for the PhD programme of the first author. The authors would also like to acknowledge the UK Engineering and Physical Sciences Research (EPSRC) for the following research grants: Platform Grant EP/G061130/2 (Dynamic performance of large civil engineering structures: an integrated approach to management, design and assessment) and Standard Grant EP/I029567/1 (Synchronization in dynamic loading due to multiple pedestrians and occupants of vibration-sensitive structures)

Socioeconomic Impact Assessment of Integrated Industrial Estate Pantnagar, India

No Abstrac

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Computer Modeling of Platinum Reforming Reactors

Usually, the reformate that is leaving any stage of the platinum reforming reactors in terms of hydrocarbon composition is assessed by laboratory analysis. The ideal composition can only be tested through theoretical means, which in most cases is avoided because of long computation time involved. This paper, instead of using a theoretical approach has considered a computer model as means of assessing the reformate composition for three-stage fixed bed reactors in platforming unit. This is done by identifying many possible hydrocarbon transformation reactions that are peculiar to the process unit, identify the operating data, mathematically model and programme their reaction rate equations using QBasic language. In this article outlet product rate of 311363.59 kg/hr in the first, second and third reactor was obtained by modeling 275 m3/h inlet feed rate of Bayton Rouge Naphtha in the Kaduna Refinery. A manual or theoretical calculated value of 311145.22 kg/hr of outlet product rate was obtained showing a slight deviation of 0.9%.  The authors are convinced that the written computer model could be applied in the process unit because it is accurate and less time consuming

Corrosion Resistance of AA6063-Type Al-Mg-Si Alloy by Silicon Carbide in Sodium Chloride Solution for Marine Application

The present work focused on corrosion inhibition of AA6063 type Al-Mg-Si alloy in sodium chloride (NaCl) solution with a silicon carbide inhibitor, using the potentiodynamic electrochemical method. The aluminium alloy surface morphology was examined, in the as-received and as-corroded in the un-inhibited state, with scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS). The results obtained via linear polarization indicated a high corrosion potential for the unprotected as-received alloy. Equally, inhibition efficiency as high as 98.82% at 10.0 g/v silicon carbide addition was obtained with increased polarization resistance (Rp), while the current density reduced significantly for inhibited samples compared to the un-inhibited aluminium alloy. The adsorption mechanism of the inhibitor aluminium alloy follows the Langmuir adsorption isotherm. This shows that the corrosion rate of aluminium alloy with silicon carbide in NaCl environment decreased significantly with addition of the inhibito

Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis

<p>Abstract</p> <p>Background</p> <p>The most important function of collagen and elastin is to induce several mechanical parameters which are known to play a dominant role in governing mechanical properties of the blood vessels. The aortic tissue of rabbit is one of the important sources of collagen and elastin. The effects of high fat diet (HFD) on the hydroxyproline (Hyp) fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits have not been documented before. The present study was undertaken to investigate the changes in Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits during the progression of atherosclerosis. The atherosclerotic model used in this study was the New Zealand white rabbit (male; 12 weeks old). Twenty five rabbits were individually caged, and divided into control group (NOR; n = 10) and HFD group (CHO; n = 15). The control group was fed (100 g/day) of normal (NOR) diet for a period of 15 weeks. The HFD group was fed normal diet supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period of time.</p> <p>Results</p> <p>We found that the TC, LDLC, and TG (mg/dl) were significantly (p < 0.001) increased in HFD rabbits compared with control rabbits with percentage normalized changes of 1198%, 1591%, and 710%, respectively. The peptide-bound Hyp in the serum was significantly (P < 0.05) increased in HFD rabbits compared with control rabbits with percentage normalized change of 517% while it significantly (P < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 65%. The protein-bound Hyp in the serum was significantly (P < 0.01) increased in HFD rabbits compared with control rabbits with percentage normalized change of 100%; the protein-bound Hyp in the aortic tissues of control rabbits was 235.30 ± 55.14 (Mean ± SD) while it was not detectable (ND) in HFD rabbits. Total serum Hyp showed no significant (P < 0.05) change in HFD rabbits compared with control rabbits while it was significantly (P < 0.05) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73%. The total collagen was significantly (p < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73% which was supported by histological study.</p> <p>Conclusions</p> <p>These results suggest that percentage decrease in various Hyp fractions in aortic tissue of HFD rabbits are closely related to percentage decrease of collagen content in aortic tissues of HFD rabbits. These results also suggest that it may be possible to use the changes in various Hyp fractions in aortic tissues of rabbits as an important risk factor during the progression of atherosclerosis.</p