A general conservative extension theorem in process algebras with inequalities

We prove a general conservative extension theorem for transition system based process theories with easy-to-check and reasonable conditions. The core of this result is another general theorem which gives sufficient conditions for a system of operational rules and an extension of it in order to ensure conservativity, that is, provable transitions from an original term in the extension are the same as in the original system. As a simple corollary of the conservative extension theorem we prove a completeness theorem. We also prove a general theorem giving sufficient conditions to reduce the question of ground confluence modulo some equations for a large term rewriting system associated with an equational process theory to a small term rewriting system under the condition that the large system is a conservative extension of the small one. We provide many applications to show that our results are useful. The applications include (but are not limited to) various real and discrete time settings in ACP, ATP, and CCS and the notions projection, renaming, stage operator, priority, recursion, the silent step, autonomous actions, the empty process, divergence, etc

Clinical outcome comparison of Grade Group 1 and Grade Group 2 prostate cancer with and without cribriform architecture at the time of radical prostatectomy

Aims: Invasive cribriform and intraductal carcinoma are associated with aggressive disease in Grade Group 2 (GG2) prostate cancer patients. However, the characteristics and clinical outcome of patients with GG2 prostate cancer without cribriform architecture (GG2−) as compared with those with Grade Group 1 (GG1) prostate cancer are unknown. The aim of this study was to investigate the clinical and pathological characteristics of GG1 and GG2− prostate cancer in radical prostatectomy specimens. Methods and results: We reviewed 835 radical prostatectomy specimens for Grade Group, pT stage, surgical margin status, and the presence of cribriform architecture. Biochemical recurrence-free survival and metastasis were used as clinical outcomes. GG1 prostate cancer was seen in 207 patients, and GG2 prostate cancer was seen in 420 patients, of whom 228 (54%) showed cribriform architecture (GG2+) and 192 (46%) did not. GG2− patients had higher prostate-specific antigen levels (9.4 ng/ml versus 7.0 ng/ml; P < 0.001), more often had extraprostatic extension (36% versus 11%; P < 0.001) and had more positive surgical margins (27% versus 17%; P = 0.01) than GG1 patients. GG2− patients ha

Sensitivity of peatland litter decomposition to changes in temperature and rainfall

Changes to climate are projected over the next 50 years for many peatland areas. As decomposition of peatforming vegetation is likely to be intrinsically linked to these changes in climate, a clear understanding of climate-peat dynamics is required. There is concern that increased temperature and decreased precipitation could increase the rate of decomposition and put the carbon sink status of many peatlands at risk, yet few studies have examined the impact of both climatic factors together. To better understand the sensitivity of peatland decomposition to changes in both temperature and precipitation and their interaction, we conducted a shortterm laboratory experiment in which plant litters and peat soil were incubated, in isolation, in a factorial design. Treatments simulated baseline and projected climate averages derived from the latest UK climate change projections (UKCP09) for Exmoor, a climatically marginal peatland in SW England. Regular carbon dioxide flux measurements were made throughout the simulation, as well as total mass loss and total dissolved organic carbon (DOC) leached. The largest effect on carbon loss in this multifactor experiment was from substrate, with Sphagnum/peat releasing significantly less C in total during the experiment than dwarf shrubs/graminoids. Climate effects were substrate specific, with the drier rainfall treatment increasing the DOC leaching from Calluna, but decreasing it from Sphagnum. Partitioning between CO2 and DOC was also affected by climate, but only for the peat and Sphagnum samples, where the future climate scenarios (warmer and drier) resulted in a greater proportion of C lost in gaseous form. These results suggest that indirect effects of climate through changes in species composition in peatlands could ultimately turn out to be more important for litter decomposition than direct effects of climate change from increased temperatures and decreased rainfall

Analysing surface energy balance closure and partitioning over a semi-arid savanna FLUXNET site in Skukuza, Kruger National Park, South Africa

Flux towers provide essential terrestrial climate, water, and radiation budget information needed for environmental monitoring and evaluation of climate change impacts on ecosystems and society in general. They are also intended for calibration and validation of satellite-based Earth observation and monitoring efforts, such as assessment of evapotranspiration from land and vegetation surfaces using surface energy balance approaches. In this paper, 15 years of Skukuza eddy covariance data, i.e. from 2000 to 2014, were analysed for surface energy balance closure (EBC) and partitioning. The surface energy balance closure was evaluated using the ordinary least squares regression (OLS) of turbulent energy fluxes (sensible (H) and latent heat (LE)) against available energy (net radiation (Rn) less soil heat (G)), and the energy balance ratio (EBR). Partitioning of the surface energy during the wet and dry seasons was also investigated, as well as how it is affected by atmospheric vapour pressure deficit (VPD), and net radiation. After filtering years with low-quality data (2004–2008), our results show an overall mean EBR of 0.93. Seasonal variations of EBR also showed the wet season with 1.17 and spring (1.02) being closest to unity, with the dry season (0.70) having the highest imbalance. Nocturnal surface energy closure was very low at 0.26, and this was linked to low friction velocity during night-time, with results showing an increase in closure with increase in friction velocity. The energy partition analysis showed that sensible heat flux is the dominant portion of net radiation, especially between March and October, followed by latent heat flux, and lastly the soil heat flux, and during the wet season where latent heat flux dominated sensible heat flux. An increase in net radiation was characterized by an increase in both LE and H, with LE showing a higher rate of increase than H in the wet season, and the reverse happening during the dry season. An increase in VPD is correlated with a decrease in LE and increase in H during the wet season, and an increase in both fluxes during the dry season

Evaluation of six methylation markers derived from genome-wide screens for detection of cervical precancer and cancer

Aim: To evaluate the triage performance of six host-cell DNA methylation markers derived from two genome-wide discovery screens for detection of cervical precancer (cervical intraepithelial neoplasia 3 [CIN]) and cancer. Materials & methods: Human papillomavirus-positive cervical scrapes of controls (≤CIN1; n = 352) and women diagnosed with CIN3 (n = 175) or cervical cancer (n = 50) were analyzed for methylation of ASCL1, LHX8, ST6GALNAC5, GHSR, SST and ZIC1. Results: Methylation levels increased significantly with disease severity (all markers p 0.800 after leave-one-out cross-validation. Bi-marker panel ASCL1/LHX8 had highest area under the curve (0.882), and detected 83.4% of CIN3 and all cervical cancers at specificity of 82.4%. Conclusion: All six methylation markers showed an equivalent, high performance for the triage of human papillomavirus-positive women using cervical scrapes with complementarity between markers

Validation of the FAM19A4/mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women

Objectives DNA methylation analysis of cancer-related genes is a promising tool for HPV-positive women to identify those with cervical (pre)cancer (CIN3+) in need of treatment. However, clinical performance of methylation markers can be influenced by the sample type utilized. We describe a multiplex quantitative methylation-specific PCR that targets FAM19A4 and mir124-2 loci, to detect CIN3+ using both HPV-positive lavage- and brush self-samples. Methods We determined methylation thresholds for clinical classification using HPV-positive training sets comprising lavage self-samples of 182 women (including 40 with CIN3+) and brush self-samples of 224 women (including 61 with CIN3+). Subsequently, independent HPV-positive validation sets of 389 lavage self-samples (including 78 with CIN3+), and 254 brush self-samples (including 72 with CIN3+) were tested using the preset thresholds. Furthermore, the clinical performance of combined methylation analysis and HPV16/18 genotyping was determined. Results Training set analysis revealed similar FAM19A4 and mir124-2 thresholds for both self-sample types to yield highest CIN3+ sensitivity at 70% specificity. Validation set analysis resulted in a CIN3+ sensitivity of 70.5% (95%CI: 60.4-80.6) at a specificity of 67.8% (95%CI: 62.7-73.0) for lavage self-samples, and a CIN3+ sensitivity of 69.4% (95%CI: 58.8-80.1) at a 76.4% (95%CI: 70.2-82.6) specificity for brush self-samples. In combination with HPV16/18 genotyping, CIN3+ sensitivity and specificity were 88.5% (95%CI: 81.4-95.6) and 46.0% (95%CI: 40.4-51.5) for lavage self-samples, and 84.7% (95%CI: 76.4-93.0) and 54.9% (95%CI: 47.7-62.2) for brush self-samples. Conclusions FAM19A4/mir124-2 methylation analysis performs equally well in HPV-positive la

Concordance of cribriform architecture in matched prostate cancer biopsy and radical prostatectomy specimens

Aims: Invasive cribriform and/or intraductal carcinoma have been identified as independent adverse parameters for prostate cancer outcome. Little is known on biopsy undersampling of cribriform architecture. Our aim was to determine the extent of cribriform architecture undersampling and to find predictive factors for identifying false cribriform-negative cases. Methods and results: We reviewed 186 matched prostate biopsies and radical prostatectomy specimens. Of 97 biopsy grade group 2 (Gleason score 3 + 4 = 7) patients, 22 (23%) had true cribriform-negative (TN), 39 (40%) false-negative (FN) and 36 (37%) true-positive (TP) biopsies. Patients with FN biopsies had higher, although not statistically significant (P = 0.06), median PSA levels than patients with TP biopsies (12 versus 8 ng/ml). A PI-RADS 5 lesion was present in nine of 16 (54%) FN and three of 11 (27%) TN biopsies (P = 0.05). Positive biopsy rate (P = 0.47), percentage Gleason pattern 4 (P = 0.55) and glomeruloid architecture (P = 1.0) were not different. Logistic regression identified PSA as an independent pr

Case report: High-resolution, intra-operative µDoppler-imaging of spinal cord hemangioblastoma

Surgical resection of spinal cord hemangioblastomas remains a challenging endeavor: the neurosurgeon’s aim to reach total tumor resections directly endangers their aim to minimize post-operative neurological deficits. The currently available tools to guide the neurosurgeon’s intra-operative decision-making consist mostly of pre-operative imaging techniques such as MRI or MRA, which cannot cater to intra-operative changes in field of view. For a while now, spinal cord surgeons have adopted ultrasound and its submodalities such as Doppler and CEUS as intra-operative techniques, given their many benefits such as real-time feedback, mobility and ease of use. However, for highly vascularized lesions such as hemangioblastomas, which contain up to capillary-level microvasculature, having access to higher-resolution intra-operative vascular imaging could potentially be highly beneficial. µDoppler-imaging is a new imaging modality especially fit for high-resolution hemodynamic imaging. Over the last decade, µDoppler-imaging has emerged as a high-resolution, contrast-free sonography-based technique which relies on High-Frame-Rate (HFR)-ultrasound and subsequent Doppler processing. In contrast to conventional millimeter-scale (Doppler) ultrasound, the µDoppler technique has a higher sensitivity to detect slow flow in the entire field-of-view which allows for unprecedented visualization of blood flow down to sub-millimeter resolution. In contrast to CEUS, µDoppler is able to image high-resolution details continuously, without being contrast bolus-dependent. Previously, our team has demonstrated the use of this technique in the context of functional brain mapping during awake brain tumor resections and surgical resections of cerebral arteriovenous malformations (AVM). However, the application of µDoppler-imaging in the context of the spinal cord has remained restricted to a handful of mostly pre-clinical animal studies. Here we describe the first application of µDoppler-imaging in the case of a patient with two thoracic spinal hemangioblastomas. We demonstrate how µDoppler is able to identify intra-operatively and with high-resolution, hemodynamic features of the lesion. In contrast to pre-operative MRA, µDoppler could identify intralesional vascular details, in real-time during the surgical procedure. Additionally, we show highly detailed post-resection images of physiological human spinal cord anatomy. Finally, we discuss the necessary future steps to push µDoppler to reach actual clinical maturity