Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial

Background: The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. / Purpose: To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. / Materials and Methods: In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3–5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. / Results: Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). / Conclusion: An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings

Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone: the PROMIS study.

Background Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy.Objectives To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway.Design A validating paired-cohort study and an economic evaluation using a decision-analytic model.Setting Eleven NHS hospitals in England.Participants Men at risk of prostate cancer undergoing a first prostate biopsy.Interventions Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test).Main outcome measures Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy.Results Diagnostic study - a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation - the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer.Limitations The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy.Conclusions Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission.Trial registration Current Controlled Trials ISRCTN16082556 and NCT01292291.Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council's Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK

Leaf litter hides post-dispersed seeds from invasive alien removers in a sclerophyll forest in central Chile

Aim of the study: Seed removal may be a determining filter for regeneration. Factors such as leaf litter, tree cover and seed density affect seed removal. This aims to assess three aspects involving on post dispersal seed removal of four woody species (Lithraea caustica, Maytenus boaria, Quillaja saponaria and Retanilla ephedra) of a sclerophyll forest.Study area: Andean Mediterranean sclerophyll forest of Quillaja saponaria and Lithraea caustica located in the Río de Los Cipreses National Reserve, Chile.Materials and methods: Seven experimental plots were set up, in which seeds were offered in an experiment with variations in leaf litter, tree cover and seed density. Generalized Linear Mixed Models (GLMM) were used for the statistical analysis. Camera traps were installed to identify the seed removers.Main results: Q. saponaria seeds were more removed than the seeds of the other species (0.84, observed mean). Whereas that M. boaria and R. ephedra did not show significant differences on the removal of their seeds (0.77 and 0.67 respectively), both were more removed than L. caustica (0.59). The removal of M. boaria, Q. saponaria and R. ephedra seeds was lower in the presence of leaf litter. No factor influenced the removal of L. caustica seeds. Seed removers were identified as invasive alien species such as Rattus sp. and Oryctolagus cuniculus and native species such as Lycalopex culpaeus.Research highlights: Three woody species of this forest suffer severe seed removal by invasive alien fauna with major implications for the resilience of these forests. The coverage of leaf litter is key to hide away the seeds, increasing survival and could promote germination.Keywords: invasive alien fauna; Mediterranean forest; sclerophyll forest; seed removal factors

Leaf litter hides post-dispersed seeds from invasive alien removers in a sclerophyll forest in central Chile

Aim of the study: Seed removal may be a determining filter for regeneration. Factors such as leaf litter, tree cover and seed density affect seed removal. This aims to assess three aspects involving on post dispersal seed removal of four woody species (Lithraea caustica, Maytenus boaria, Quillaja saponaria and Retanilla ephedra) of a sclerophyll forest. Study area: Andean Mediterranean sclerophyll forest of Quillaja saponaria and Lithraea caustica located in the Río de Los Cipreses National Reserve, Chile. Materials and methods: Seven experimental plots were set up, in which seeds were offered in an experiment with variations in leaf litter, tree cover and seed density. Generalized Linear Mixed Models (GLMM) were used for the statistical analysis. Camera traps were installed to identify the seed removers. Main results: Q. saponaria seeds were more removed than the seeds of the other species (0.84, observed mean). Whereas that M. boaria and R. ephedra did not show significant differences on the removal of their seeds (0.77 and 0.67 respectively), both were more removed than L. caustica (0.59). The removal of M. boaria, Q. saponaria and R. ephedra seeds was lower in the presence of leaf litter. No factor influenced the removal of L. caustica seeds. Seed removers were identified as invasive alien species such as Rattus sp. and Oryctolagus cuniculus and native species such as Lycalopex culpaeus. Research highlights: Three woody species of this forest suffer severe seed removal by invasive alien fauna with major implications for the resilience of these forests. The coverage of leaf litter is key to hide away the seeds, increasing survival and could promote germination

Effects of canopy gaps on forest floor vascular and non-vascular plant species composition and diversity in an uneven-aged Nothofagus betuloides forest in Tierra del Fuego, Chile

Canopy gaps modify the environmental conditions available for plant growth in forests. Small canopy gaps are frequent in Nothofagus betuloides forests of Tierra del Fuego. Our objective was to study whether the forest floor vascular and non-vascular plant species composition and diversity are influenced by the occurrence of small-scale disturbances due to changes in the below-canopy solar radiation transmittances and forest floor heterogeneity (cover of litter, bare soil and fallen woody debris classed in three decay stages) in a N. betuloides forest located in south western Tierra del Fuego (53° 59t’S, 69°58′W). The vegetation was sampled in and around 13 canopy gaps (47 m2 on average). Following a light gradient, 65 plots (2 × 2 m) were established. The cover of all plant species was recorded using Londo’s scale. Species richness and total cover were calculated for each of the following taxonomical groups: spermatophyta (monocotyledons, dicotyledons), pteridophyta, bryophyta, marchantiophyta, anthocerotophyta and lichens. There were 63 species found on the forest floor. Marchantiophyta was the most diverse group with the highest species richness (6.6 species per plot). The vegetation on the forest floor was very homogeneous in species composition, richness and species diversity. The ordination analysis (NMS) showed that the community composition was weakly influenced by the patterns of below-canopy solar radiation transmittances and substrate heterogeneity. MRPP analysis of the community composition did not reveal differences in plant species assemblages between positions along transects running from areas beneath closed canopy to the open centres of canopy gaps. The marchantiophyte Chiloscyphus magellanicus was the only species which can be considered to be an indicator species; it was more likely to occur in gap centres (more open conditions). We conclude that these small canopy gaps do not very much modify the forest floor communities and the communities can be considered relatively stable

Moisture hysteresis influence on mass transfer through bio-based building materials in dynamic state

International audienceBio-based materials are increasingly present in the constitution of the building envelops thanks to their numerous advantages such as good thermo-hygric performances, weak environmental impact, efficient regulation of the perceived indoor air quality and human comfort... The analysis of moisture transfer is necessary to increase the efficiency of these materials and to ensure building sustainability. Actually, most of hygrothermal models neglect the moisture hysteresis effect, arguing the weak impact on the obtained results. Thus, a 3D numerical model was built on COMSOL Multiphysics, taking into account the hysteresis phenomenon to assess the impact of hysteresis effects. The model was validated thanks to experimental tests performed on hemp concrete and rape straw concrete. Tests were carried out under various dynamic hygric solicitations, with a regulated climatic chamber. The results have been compared in steady and transient states, with and without the effect of moisture hysteresis. Results have shown that hysteresis could be neglected in steady state, if the relative humidity range did not reach the capillary condensation. In this case, a model based on the main adsorption isotherm could lead to reasonable approximation, with weak calculation costs. For the analysis of a wall under real climatic solicitations, which corresponds to a non-steady state, neglecting the moisture hysteresis could lead to significant discrepancies, especially in terms of sample moist mass (and consequently moisture content or absolute humidity). (C) 2018 Elsevier B.V. All rights reserved

PROMIS - Prostate MR imaging study:A paired validating cohort study evaluating the role of multi-parametric MRI in men with clinical suspicion of prostate cancer

* Background: Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway.  * Methods: PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10-12 core TRUS-biopsy (standard) and 5. mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others.  * Results: PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers. For the primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4 + 3 and/or maximum cancer core length of ≥ 6 mm. PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes. Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated. Conclusions: PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinically-significant cancer