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Abstract Background For patients with a higher burden of localized prostate cancer, radiation dose escalation with brachytherapy boosts have improved cancer control outcomes at the cost of urinary toxicity. We hypothesize that a focal approach to brachytherapy boosts targeting only grossly visualized tumor volumes (GTV) combined with stereotactic radiotherapy will improve quality of life (QoL) outcomes without compromising cancer control. Methods 150 patients with intermediate or high-risk prostate cancer will be enrolled and randomized 1:1 in a cohort multiple randomized clinical trial phase 2 design. Patients are eligible if planned for standard-of-care (SOC) high dose rate (HDR) brachytherapy boost to radiotherapy (RT) with GTVs encompassing

Objectives: Understanding the drivers of delays from diagnosis to treatment can elucidate how to reduce the time to treatment (TTT) in patients with prostate cancer. In addition, the available treatments depending on the stage of cancer can vary widely for many reasons. This study investigated the relationship of TTT and treatment choice with sociodemographic factors in patients with prostate cancer who underwent external beam radiation therapy (RT), radical prostatectomy (RP), androgen deprivation therapy (ADT), or active surveillance (AS) at a safety-net academic medical center. Methods and materials: A retrospective review was performed on 1088 patients who were diagnosed with nonmetastatic prostate cancer between January 2005 and December 2013. Demographic data as well as data on TTT, initial treatment choice, American Joint Committee on Cancer stage, and National Comprehensive Cancer Network risk categories were collected. Analyses of variance and multivariable logistic regression models were performed to analyze the relationship of these factors with treatment choice and TTT. Results: Age, race, and marital status were significantly related to treatment choice. Patients who were nonwhite and older than 60 years were less likely to undergo RP. Black patients were 3.8 times more likely to undergo RT compared with white patients. The median TTT was 75 days. Longer time delays were significant in patients of older age, nonwhite race/ethnicity, non-English speakers, those with noncommercial insurance, and those with non-married status. The average TTT of high-risk patients was 25 days longer than that of low-risk patients. Patients who underwent RT had an average TTT that was 34 days longer than that of RP patients. Conclusions: The treatment choice and TTT of patients with prostate cancer are affected by demographic factors such as age, race, marital status, and insurance, as well as clinical factors including stage and risk category of disease.

In response to the article of Szopiński et al.(1) we want to compliment the authors for a very thorough and sound review article. The authors listed the most signifi cant developments and trends in prostate ultrasound, and mentioned the increasing role of MRI in prostate cancer diagnosis and staging.

Molecular profiling of human biopsies and surgical specimens is frequently complicated by their inherent biological heterogeneity and by the need to conserve tissue for clinical diagnosis. We have developed a set of novel 'tissue print' and 'print-phoresis' technologies to facilitate tissue and tumor-marker profiling under these circumstances. Tissue printing transfers cells and extracellular matrix components from a tissue surface onto nitrocellulose membranes, generating a two-dimensional anatomical image on which molecular markers can be visualized by specific protein and RNA- and DNA-detection techniques. Print-phoresis is a complementary new electrophoresis method in which thin strips from the print are subjected to polyacrylamide gel electrophoresis, providing a straightforward interface between the tissue-print image and gel-based proteomic techniques. Here we have utilized these technologies to identify and characterize markers of tumor invasion of the prostate capsule, an event generally not apparent to the naked eye that may result in tumor at the surgical margins ('positive margins'). We have also shown that tissue-print technologies can provide a general platform for the generation of marker maps that can be superimposed directly onto histopathological and radiological images, permitting molecular identification and classification of individual malignant lesions., Author(s): Sandra M Gaston (corresponding author) [1]; Marc A Soares [1]; M Minhaj Siddiqui [2]; Dang Vu [1]; Jung M Lee [1]; Dana L Goldner [1]; Mark J Brice [1]; [...]

Purpose: In SBRT for prostate cancer, higher fractional dose to the rectum is a major toxicity concern due to using smaller PTV margin and hypofractionation. We investigate the dosimetric impact on rectum using endorectal balloon (ERB) in prostate SBRT. Materials and Methods: Twenty prostate cancer patients were included in a retrospective study, ten with ERB and 10 without ERB. Optimized SBRT plans were generated on CyberKnife MultiPlan for 5 × 7.25 Gy to PTV under RTOG-0938 protocol for early-stage prostate cancer. For the rectum and the anterior half rectum, mean dose and percentage of volumes receiving 50%, 80%, 90%, and 100% prescription dose were compared. Results: Using ERB, mean dose to the rectum was 62 cGy (P = 0.001) lower per fraction, and 50 cGy (P = 0.024) lower per fraction for the anterior half rectum. The average V50%, V80%, V90%, and V100% were lower by 9.9% (P = 0.001), 5.3% (P = 0.0002), 3.4% (P = 0.0002), and 1.2% (P = 0.005) for the rectum, and lower by 10.4% (P = 0.009), 8.3% (P = 0.0004), 5.4% (P = 0.0003), and 2.1% (P = 0.003) for the anterior half rectum. Conclusions: Significant reductions of dose to the rectum using ERB were observed. This may lead to improvement of the rectal toxicity profiles in prostate SBRT. [ABSTRACT FROM AUTHOR]

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Purpose To identify computer-extracted features for central gland and peripheral zone prostate cancer localization on multiparametric magnetic resonance imaging (MRI). Materials and Methods Preoperative T2-weighted (T2w), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) MRI were acquired from 23 men with confirmed prostate cancer. Following radical prostatectomy, the cancer extent was delineated by a pathologist on ex vivo histology and mapped to MRI by nonlinear registration of histology and corresponding MRI slices. In all, 244 computer-extracted features were extracted from MRI, and principal component analysis (PCA) was employed to reduce the data dimensionality so that a generalizable classifier could be constructed. A novel variable importance on projection (VIP) measure for PCA (PCA-VIP) was leveraged to identify computer-extracted MRI features that discriminate between cancer and normal prostate, and these features were used to construct classifiers for cancer localization. Results Classifiers using features selected by PCA-VIP yielded an area under the curve (AUC) of 0.79 and 0.85 for peripheral zone and central gland tumors, respectively. For tumor localization in the central gland, T2w, DCE, and DWI MRI features contributed 71.6%, 18.1%, and 10.2%, respectively; for peripheral zone tumors T2w, DCE, and DWI MRI contributed 29.6%, 21.7%, and 48.7%, respectively. Conclusion PCA-VIP identified relatively stable subsets of MRI features that performed well in localizing prostate cancer on MRI. J. Magn. Reson. Imaging 2015;41:1383-1393. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To assess detailed dosimetry data for prostate and clinical relevant intra- and peri-prostatic structures including neurovascular bundles (NVB), urethra, and penile bulb (PB) from postbrachytherapy computed tomography (CT) versus high resolution contrast enhanced magnetic resonance imaging (HR-CEMRI). Material and methods: Eleven postbrachytherapy prostate cancer patients underwent HR-CEMRI and CT imaging. Computed tomography and HR-CEMRI images were randomized and 2 independent expert readers created contours of prostate, intra- and peri-prostatic structures on each CT and HR-CEMRI scan for all 11 patients. Dosimetry data including V100, D90, and D100 was calculated from these contours. Results: Mean V100 values from CT and HR-CEMRI contours were as follows: prostate (98.5% and 96.2%, p = 0.003), urethra (81.0% and 88.7%, p = 0.027), anterior rectal wall (ARW) (8.9% and 2.8%, p < 0.001), left NVB (77.9% and 51.5%, p = 0.002), right NVB (69.2% and 43.1%, p = 0.001), and PB (0.09% and 11.4%, p = 0.005). Mean D90 (Gy) derived from CT and HR-CEMRI contours were: prostate (167.6 and 150.3, p = 0.012), urethra (81.6 and 109.4, p = 0.041), ARW (2.5 and 0.11, p = 0.003), left NVB (98.2 and 58.6, p = 0.001), right NVB (87.5 and 55.5, p = 0.001), and PB (11.2 and 12.4, p = 0.554). Conclusions: Findings of this study suggest that HR-CEMRI facilitates accurate and meaningful dosimetric assessment of prostate and clinically relevant structures, which is not possible with CT. Significant differences were seen between CT and HR-CEMRI, with volume overestimation of CT derived contours compared to HR-CEMRI. [ABSTRACT FROM AUTHOR]

Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain, approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping the in vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides "ground truth" mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework yielded a central gland Dice similarity coefficient (DSC) of 90%, and prostate DSC of 88%, while the misalignment of the urethra and verumontanum was found to be 3.45 mm, and 4.73 mm, respectively, which were measured to be significantly smaller compared to the alternative strategies. As might have been anticipated from our limited cohort of biopsy confirmed cancers, the disease atlas showed that most of the tumor extent was limited to the peripheral zone. Moreover, central gland tumors were typically larger in size, possibly because they are only discernible at a much later stage. Conclusions: The authors presented the AnCoR framework to explicitly model anatomic constraints for the construction of a fused anatomic imaging-disease atlas. The framework was applied to constructing a preliminary version of an anatomic-disease atlas of the prostate, the prostatome. The prostatome could facilitate the quantitative characterization of gland morphology and imaging features of prostate cancer. These techniques, may be applied on a large sample size data set to create a fully developed prostatome that could serve as a spatial prior for targeted biopsies by urologists. Additionally, the AnCoR framework could allow for incorporation of complementary imaging and molecular data, thereby enabling their careful correlation for population based radio-omics studies. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To establish the value of MRI in targeting re-biopsy for undiagnosed prostate cancer despite multiple negative biopsies and determine clinical relevance of detected tumors. Materials and Methods: Thirty-eight patients who underwent MRI after 2 or more negative biopsies due to continued clinical suspicion and later underwent TRUS-guided biopsy supplemented by biopsy of suspicious areas depicted by MRI were identified. Diagnostic performance of endorectal 3T MRI in diagnosing missed cancer foci was assessed using biopsy results as the standard of reference. Ratio of positive biopsies using systematic versus MRI-prompted approaches was compared. Gleason scores of detected cancers were used as surrogate for clinical relevance. Results: Thirty-four percent of patients who underwent MRI before re-biopsy had prostate cancer on subsequent biopsy. The positive biopsy yield with systematic sampling was 23% versus 92% with MRI-prompted biopsies(p<0.0001). Seventy-seven percent of tumors were detected exclusively in the MRI-prompted zones. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI to provide a positive biopsy were 92%, 60%, 55%, 94% and 71%, respectively. The anterior gland and apical regions contained most tumors; 75% of cancers detected by MRI-prompted biopsy had Gleason score≥7. Conclusions: Clinically relevant tumors missed by multiple TRUS-guided biopsies can be detected by a MRI-prompted approach. [Copyright &y& Elsevier]

Purpose: By performing registration of preoperative multiprotocol in vivo magnetic resonance (MR) images of the prostate with corresponding whole-mount histology (WMH) sections from postoperative radical prostatectomy specimens, an accurate estimate of the spatial extent of prostate cancer (CaP) on in vivo MR imaging (MRI) can be retrospectively established. This could allow for definition of quantitative image-based disease signatures and lead to development of classifiers for disease detection on multiprotocol in vivo MRI. Automated registration of MR and WMH images of the prostate is complicated by dissimilar image intensities, acquisition artifacts, and nonlinear shape differences. Methods: The authors present a method for automated elastic registration of multiprotocol in vivo MRI and WMH sections of the prostate. The method, multiattribute combined mutual information (MACMI), leverages all available multiprotocol image data to drive image registration using a multivariate formulation of mutual information. Results: Elastic registration using the multivariate MI formulation is demonstrated for 150 corresponding sets of prostate images from 25 patient studies with T2-weighted and dynamic-contrast enhanced MRI and 85 image sets from 15 studies with an additional functional apparent diffusion coefficient MRI series. Qualitative results of MACMI evaluation via visual inspection suggest that an accurate delineation of CaP extent on MRI is obtained. Results of quantitative evaluation on 150 clinical and 20 synthetic image sets indicate improved registration accuracy using MACMI compared to conventional pairwise mutual information-based approaches. Conclusions: The authors' approach to the registration of in vivo multiprotocol MRI and ex vivo WMH of the prostate using MACMI is unique, in that (1) information from all available image protocols is utilized to drive the registration with histology, (2) no additional, intermediate ex vivo radiology or gross histology images need be obtained in addition to the routinely acquired in vivo MRI series, and (3) no corresponding anatomical landmarks are required to be identified manually or automatically on the images. [ABSTRACT FROM AUTHOR]

Management decisions for patients with prostate cancer present a dilemma for both patients and their clinicians because prostate cancers demonstrate a wide range in biologic activity, with the majority of cases not leading to a prostate cancer related death. Furthermore, the current treatment options have significant side effects, such as incontinence, rectal injury and impotence. Key elements for guiding appropriate treatment include: distinction of organ-confined disease from extracapsular extension (ECE); and determination of tumor volume and tumor grade, none of which have been satisfactorily accomplished in today's pre-treatment paradigm. Magnetic resonance imaging (MRI) has the capability to assess prostate tissue, both functionally and morphologically. MRI as a staging tool has not shown enough consistency or sufficient accuracy for widespread adoption in clinical practice; yet, recent technical developments in MRI have yielded improved results. At our institution we have combined the use of new endorectal 3 Tesla MRI technology, T2-weighted, and high spatial resolution dynamic-contrast enhanced (DCE) MRI to non-invasively assess the prostate with higher signal-to-noise ratio and spatial resolution than previously achieved. This approach allows assessment of prostate-tissue morphology and kinetics, thus providing a non-invasive tool for tumor detection and staging and, consequently, directing biopsy and treatment specifically to diseased areas for a pre-treatment evaluation that can assist in the rational selection of patients for appropriate prostate cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with computed tomography (CT) for prostate brachytherapy seed location for dosimetric calculations. Methods and Materials: Postbrachytherapy prostate MRI was performed on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients. Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed distribution independently. The dependency of data read by both readers for a specific subject was assessed with a linear mixed effects model. Results: The mean percentage (+/- standard deviation) values of the readers for seed detection and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected 91.5% +/- 4.8%, 78.5% +/- 8.5%, and 96.1% +/- 2.3%, respectively, with 11.8% +/- 4.5%, 8.5% +/- 3.5%, 1.9% +/- 1.0% extracapsular, respectively. Assignment to periprostatic structures was not possible with CT. Periprostatic seed assignments for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% +/- 1.6% and 2.1% +/- 0.9%; seminal vesicles, 0.9% +/- 1.8% and 0.3% +/- 0.7%; periurethral, 7.1% +/- 3.3% and 5.8% +/- 2.9%; penile bulb, 0.6% +/- 0.8% and 0.3% +/- 0.6%; Denonvillier's Fascia/rectal wall, 0.5% +/- 0.6% and 0%; and urinary bladder, 0.1% +/- 0.3% and 0%. Data dependency analysis showed statistical significance for the type of imaging but not for reader identification. Conclusion: Both enumeration and localization of implanted seeds are readily accomplished with CEMR. Calculations with MRI dosimetry do not require CT data. Dose determinations to specific extracapsular sites can be obtained with MRI but not with CT. [ABSTRACT FROM AUTHOR]

Most prostate MRI/MRS examinations are performed with an endorectal coil inflated with air, leading to an air-tissue interface that induces magnetic susceptibility gradients within the gland. Inflation of the coil with a barium sulfate suspension is described and compared to inflation with air or liquid perfluorocarbon (PFC). The B0 field in the prostate gland was mapped for five healthy volunteers when the endorectal coil was inflated with each of the three agents. A marked decrease in the posterior-anterior (P-A) field gradient and a significant improvement in field homogeneity were evident in the presence of a barium suspension and PFC relative to air. MRS data acquired from the prostate gland in the presence of air, PFC, and a barium suspension in the endorectal coil showed similar trends, demonstrating improvement in line-widths and spectral resolution when the barium suspension or the PFC were inflating the endorectal coil. On this basis we conclude that a barium suspension provides an available, cheap, and safe alternative to PFC, and we suggest that inflating the endorectal coil with a barium suspension should be considered for prostate MR studies, especially at high field strengths (such as 3T). Magn Reson Med 57:898-904, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Rationale and objectives: High-resolution magnetic resonance imaging of the prostate at 1.5T has gained acceptance for pretherapeutic staging of prostate cancer. The aim of this study was to evaluate the potential clinical utility of combined pelvic phased-array and endorectal coils at 3T.Materials and methods: Six volunteers were examined on 1.5T and 3T scanners with pelvic phased-array surface coil combined with a disposable endorectal prostate coil.Results: We were able to acquire T2-W fast spin echo images with 1.5 mm slices, field of view 12, matrix 320 × 192, (voxel size 0.35 mm3), with excellent anatomic detail and good T2 contrast. A 1.5 mm axial slice thickness permitted high-quality multiplanar reconstructions with clear visualization of small patho-anatomic structures. Dynamic contrast-enhanced gradient echo images showed excellent spatial resolution (voxel size, 0.38 mm3) and temporal resolution. With this level of anatomic information in dynamic images we could clearly distinguish between intracapsular and extracapsular contrast enhancement.Conclusion: Using modified T2-fast spin echo and dynamic contrast-enhanced gradient echo sequences, we obtained whole gland coverage with 35–38 μm3 resolution, without interfering artifacts, in reasonable acquisition times and staying well below the specific absorption rate guidelines. The high spatial resolution in the axial plane allowed meaningful multiplanar reconstructions. The initial results show the clinical utility of endorectal 3T for the noninvasive evaluation of the prostate with image features and quality not achievable at 1.5 T. [Copyright &y& Elsevier]

Background: For most computer-aided diagnosis (CAD) problems involving prostate cancer detection via medical imaging data, the choice of classifier has been largely ad hoc, or been motivated by classifier comparison studies that have involved large synthetic datasets. More significantly, it is currently unknown how classifier choices and trends generalize across multiple institutions, due to heterogeneous acquisition and intensity characteristics (especially when considering MR imaging data). In this work, we empirically evaluate and compare a number of different classifiers and classifier ensembles in a multi-site setting, for voxel-wise detection of prostate cancer (PCa) using radiomic texture features derived from high-resolution in vivo T2-weighted (T2w) MRI. Methods: Twelve different supervised classifier schemes: Quadratic Discriminant Analysis (QDA), Support Vector Machines (SVMs), naïve Bayes, Decision Trees (DTs), and their ensemble variants (bagging, boosting), were compared in terms of classification accuracy as well as execution time. Our study utilized 85 prostate cancer T2w MRI datasets acquired from across 3 different institutions (1 for discovery, 2 for independent validation), from patients who later underwent radical prostatectomy. Surrogate ground truth for disease extent on MRI was established by expert annotation of pre-operative MRI through spatial correlation with corresponding ex vivo whole-mount histology sections. Classifier accuracy in detecting PCa extent on MRI on a per-voxel basis was evaluated via area under the ROC curve. Results: The boosted DT classifier yielded the highest cross-validated AUC (= 0.744) for detecting PCa in the discovery cohort. However, in independent validation, the boosted QDA classifier was identified as the most accurate and robust for voxel-wise detection of PCa extent (AUCs of 0.735, 0.683, 0.768 across the 3 sites). The next most accurate and robust classifier was the single QDA classifier, which also enjoyed the advantage of significantly lower computation times compared to any of the other methods. Conclusions: Our results therefore suggest that simpler classifiers (such as QDA and its ensemble variants) may be more robust, accurate, and efficient for prostate cancer CAD problems, especially in the context of multi-site validation. [ABSTRACT FROM AUTHOR]

In the framework of ChArMEx (the Chemistry-Aerosol Mediterranean Experiment), the air quality model Polyphemus is used to understand the sources of inorganic and organic particles in the western Mediterranean and evaluate the uncertainties linked to the model parameters (meteorological fields, anthropogenic and sea-salt emissions and hypotheses related to the model representation of condensation/evaporation). The model is evaluated by comparisons to in situ aerosol measurements performed during three consecutive summers (2012, 2013 and 2014). The model-to-measurement comparisons concern the concentrations of PM10, PM1, organic matter in PM1 (OM1) and inorganic aerosol concentrations monitored at a remote site (Ersa) on Corsica Island, as well as airborne measurements performed above the western Mediterranean Sea. Organic particles are mostly from biogenic origin. The model parameterization of sea-salt emissions has been shown to strongly influence the concentrations of all particulate species (PM10, PM1, OM1 and inorganic concentrations). Although the emission of organic matter by the sea has been shown to be low, organic concentrations are influenced by sea-salt emissions; this is owing to the fact that they provide a mass onto which gaseous hydrophilic organic compounds can condense. PM10, PM1, OM1 are also very sensitive to meteorology, which affects not only the transport of pollutants but also natural emissions (biogenic and sea salt). To avoid large and unrealistic sea-salt concentrations, a parameterization with an adequate wind speed power law is chosen. Sulfate is shown to be strongly influenced by anthropogenic (ship) emissions. PM10, PM1, OM1 and sulfate concentrations are better described using the emission inventory with the best spatial description of ship emissions (EDGAR-HTAP). However, this is not true for nitrate, ammonium and chloride concentrations, which are very dependent on the hypotheses used in the model regarding condensation/evaporation. Model simulations show that sea-salt aerosols above the sea are not mixed with background transported aerosols. Taking the mixing state of particles with a dynamic approach to condensation/evaporation into account may be necessary to accurately represent inorganic aerosol concentrations.

The present study aims at identifying and apportioning fine aerosols to their major sources in Paris (France) – the second most populated "larger urban zone" in Europe – and determining their geographical origins. It is based on the daily chemical composition of PM2.5 examined over 1 year at an urban background site of Paris (Bressi et al., 2013). Positive matrix factorization (EPA PMF3.0) was used to identify and apportion fine aerosols to their sources; bootstrapping was performed to determine the adequate number of PMF factors, and statistics (root mean square error, coefficient of determination, etc.) were examined to better model PM2.5 mass and chemical components. Potential source contribution function (PSCF) and conditional probability function (CPF) allowed the geographical origins of the sources to be assessed; special attention was paid to implement suitable weighting functions. Seven factors, namely ammonium sulfate (A.S.)-rich factor, ammonium nitrate (A.N.)-rich factor, heavy oil combustion, road traffic, biomass burning, marine aerosols and metal industry, were identified; a detailed discussion of their chemical characteristics is reported. They contribute 27, 24, 17, 14, 12, 6 and 1% of PM2.5 mass (14.7 μg m−3) respectively on the annual average; their seasonal variability is discussed. The A.S.- and A.N.-rich factors have undergone mid- or long-range transport from continental Europe; heavy oil combustion mainly stems from northern France and the English Channel, whereas road traffic and biomass burning are primarily locally emitted. Therefore, on average more than half of PM2.5 mass measured in the city of Paris is due to mid- or long-range transport of secondary aerosols stemming from continental Europe, whereas local sources only contribute a quarter of the annual averaged mass. These results imply that fine-aerosol abatement policies conducted at the local scale may not be sufficient to notably reduce PM2.5 levels at urban background sites in Paris, suggesting instead more coordinated strategies amongst neighbouring countries. Similar conclusions might be drawn in other continental urban background sites given the transboundary nature of PM2.5 pollution.

Studies describing the chemical composition of fine aerosol (PM2.5) in urban areas are often conducted for a few weeks only and at one sole site, giving thus a narrow view of their temporal and spatial characteristics. This paper presents a one-year (11 September 2009–10 September 2010) survey of the daily chemical composition of PM2.5 in the region of Paris, which is the second most populated "Larger Urban Zone" in Europe. Five sampling sites representative of suburban (SUB), urban (URB), northeast (NER), northwest (NWR) and south (SOR) rural backgrounds were implemented. The major chemical components of PM2.5 were determined including elemental carbon (EC), organic carbon (OC), and the major ions. OC was converted to organic matter (OM) using the chemical mass closure methodology, which leads to conversion factors of 1.95 for the SUB and URB sites, and 2.05 for the three rural ones. On average, gravimetrically determined PM2.5 annual mass concentrations are 15.2, 14.8, 12.6, 11.7 and 10.8 μg m−3 for SUB, URB, NER, NWR and SOR sites, respectively. The chemical composition of fine aerosol is very homogeneous at the five sites and is composed of OM (38–47%), nitrate (17–22%), non-sea-salt sulfate (13–16%), ammonium (10–12%), EC (4–10%), mineral dust (2–5%) and sea salt (3–4%). This chemical composition is in agreement with those reported in the literature for most European environments. On an annual scale, Paris (URB and SUB sites) exhibits its highest PM2.5 concentrations during late autumn, winter and early spring (higher than 15 μg m−3 on average, from December to April), intermediates during late spring and early autumn (between 10 and 15 μg m−3 during May, June, September, October, and November) and the lowest during summer (below 10 μg m−3 during July and August). PM levels are mostly homogeneous on a regional scale, during the whole project (e.g. for URB plotted against NER sites: slope = 1.06, r2=0.84, n=330), suggesting the importance of mid- or long-range transport, and regional instead of local scale phenomena. During this one-year project, two thirds of the days exceeding the PM2.5 2015 EU annual limit value of 25 μg m−3 were due to continental import from countries located northeast, east of France. This result questions the efficiency of local, regional and even national abatement strategies during pollution episodes, pointing to the need for a wider collaborative work with the neighbouring countries on these topics. Nevertheless, emissions of local anthropogenic sources lead to higher levels at the URB and SUB sites compared to the others (e.g. 26% higher on average at the URB than at the NWR site for PM2.5, during the whole campaign), which can even be emphasised by specific meteorological conditions such as low boundary layer heights. OM and secondary inorganic species (nitrate, non-sea-salt sulfate and ammonium, noted SIA) are mainly imported by mid- or long-range transport (e.g. for NWR plotted against URB sites: slope = 0.79, r2=0.72, n=335 for OM, and slope = 0.91, r2=0.89, n=335 for SIA) whereas EC is primarily locally emitted (e.g. for SOR plotted against URB sites: slope = 0.27; r2=0.03; n=335). This database will serve as a basis for investigating carbonaceous aerosols, metals as well as the main sources and geographical origins of PM in the region of Paris.

The effect of a post-industrial megacity on local and regional air quality was assessed via a month-long field measurement campaign in the Paris metropolitan area during winter 2010. Here we present source apportionment results from three aerosol mass spectrometers and two aethalometers deployed at three measurement stations within the Paris region. Submicron aerosol composition is dominated by the organic fraction (30–36%) and nitrate (28–29%), with lower contributions from sulfate (14–16%), ammonium (12–14%) and black carbon (7–13%). Organic source apportionment was performed using positive matrix factorization, resulting in a set of organic factors corresponding both to primary emission sources and secondary production. The dominant primary sources are traffic (11–15% of organic mass), biomass burning (13–15%) and cooking (up to 35% during meal hours). Secondary organic aerosol contributes more than 50% to the total organic mass and includes a highly oxidized factor from indeterminate and/or diverse sources and a less oxidized factor related to wood burning emissions. Black carbon was apportioned to traffic and wood burning sources using a model based on wavelength-dependent light absorption of these two combustion sources. The time series of organic and black carbon factors from related sources were strongly correlated. The similarities in aerosol composition, total mass and temporal variation between the three sites suggest that particulate pollution in Paris is dominated by regional factors, and that the emissions from Paris itself have a relatively low impact on its surroundings.

Abstract: Purpose: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). Materials and methods: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. Results: Twenty-four polyps were detected in eighteen patients with CC (5 polyps ≥10mm, 4 polyps 6–9mm, 15 polyps ≤5mm). MRC was 66.7% (12/18) sensitive and 96.4% (27/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5/5) and 100% (19/19), respectively, for lesions greater than 10mm, 100% (4/4) and 100% (20/20) for lesions 6–9mm, and sensitivity of 20% (3/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9/9) and 100% (15/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n =16) of patients preferred MRC as a future screening test compared to 33% (n =15) for CC. Conclusion: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps ≥6mm in size. Further studies are warranted. [Copyright &y& Elsevier]

The use of particle localisation and tracking algorithms on Contrast Enhanced Ultrasound (CEUS) or other ultrasound mode image data containing sparse microbubble (MB) populations, can produce super-resolved vascularization maps. Typically such data stem from conventional delay and sum (DAS) beamforming that is used widely in ultrasound imaging modes. Recently, adaptive beamforming has shown significant improvement in spatial resolution, but its value to super-resolution image analysis approaches is not fully understood. The in silico study here evaluates the performance of combining minimum variance beamformers (MV BF), established to provide improved lateral resolution, compared to DAS BFs with single particle detection. The isolated effect of a range of simplified image-affecting factors such as flow profile, pulse length, noise, vessel separations and data availability is considered. The study aims to assess the vessel recovery performance using the different beamformers and investigate the link with MB detection and localisation. The MV BF was shown to provide improved microvessel position accuracy compared to conventional DAS BFs. In particular, vessel separations between 0.3-4 λ provided superior localisation uncertainty with the MV. In addition, for a separation of 0.36λ, vessel recovery was achieved with both methods but the use of MV eliminated artifacts that appear as additional vessels. These results were found to be linked to improved MB detection and localisation for the MV BF, which is proposed as suitable for testing in Ultrasound Localisation Microscopy (ULM) imaging using patient data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: In recent years, there has been significant advancement in the guidelines for recovery protocols involving heat or cold water immersion. However, comparison between the effects of hot and cold water immersion on key markers of neuromuscular recovery following exercise-induced muscle damage (EIMD) is lacking., Methods: Thirty physically active males completed an individualized and tailored EIMD protocol immediately followed by one of the following recovery interventions: cold water immersion (11°C, CWI 11 ), hot water immersion (41°C, HWI 41 ), or warm-bath control (36°C, CON 36 ). Gastrointestinal temperature was tracked throughout HWI 41 . Knee extensors' maximal isokinetic strength (peak torque ( Tpeak )) and explosive strength (late-phase rate of force development (RFD 100-200 )) were measured before EIMD (pre-), 24 h (post-24 h), and 48 h (post-48 h) post-EIMD. In addition, pressure pain threshold (PPT) was measured to quantify the recovery from muscle soreness. Surface electromyography signals (sEMG) from the vastus lateralis were captured to extract the rates of electromyography rise (REMGR) and the spectral power in the low-frequency band., Results: At post-48 h, Tpeak returned to baseline values following both CWI 11 (-8.3% ± 6.8%, P = 0.079) and HWI 41 (-1.4% ± 4.1%, P = 1). In contrast, RFD 100-200 (-2.3% ± 29.3%, P = 1) and PPT (+5.6% ± 14.6%, P = 1) returned to baseline values at post-48 h only following HWI 41 . Spectral analysis of the sEMG signal revealed that the low-frequency band was significantly increased following CWI 11 (+9.0% ± 0.52%, P = 0.012). REMGR was unchanged regardless of the condition (all P > 0.05)., Conclusions: A single session of HWI 41 , rather than CWI 11 , improved the recovery of the late-phase rate of force development following EIMD in physically active males. This suggests that in athletic contexts where a rapid force development is a key performance determinant, hot bath should be preferred over cold bath., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Telerehabilitation (TR), a branch of telemedicine, provides remote therapeutic rehabilitation through telecommunication. Driven by technological advances and benefits like remote monitoring and patient education, it has grown since 1998. The Coronavirus Disease 2019 (COVID-19) pandemic highlighted its importance in maintaining healthcare access., Research Question: What is the efficacy of TR compared to in-person rehabilitation? Are the assessment tools effective? Is TR well-accepted, and are costs reduced?, Methods: A bibliographic search on Medline, Cochrane and Google Scholar focused on systematic reviews (SRs) from 2014 to Mai 2024, comparing TR or home-based rehabilitation with in person treatments for various conditions. Independent reviewers conducted initial screenings, resolving disagreements by a third reviewer. Joanna Briggs Institute Critical Appraisal Checklist was used to evaluate the quality of review. The data was synthesised narratively., Results: The search identified 665 SRs. After selection, 228 SR were included. TR models include synchronous (real-time video interactions), asynchronous (independent sessions through digital platforms) and mixed methods. Regardless of the medical fields, the conclusions of the SRs consistently point to the equivalence of TR compared to in-person rehabilitation. Remote evaluations via digital tools were reliable and valid for various assessments. TR is cost effectiveness and well accepted., Conclusions: TR is a viable alternative or complement to traditional rehabilitation, offering enhanced accessibility, reduced costs and improved results. Barriers include technical issues, training and concerns about lack of physical contact. Mixed methods could address these challenges., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies., Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose., Results: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors., Conclusions: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

The Mental Health Service of Trento has consistently adopted a community-based, recovery-oriented approach. Adhering to these paradigms, and aiming to facilitate an intervention centred on the individual and their needs within their familial and social context, it is imperative to ensure a prompt and effective response to crises at the community level. Psychiatric emergencies present a significant challenge for health systems globally. Timely and appropriate management of these crises is crucial to prevent negative short and long-term outcomes. Providing such management in an extra-hospital setting, adaptable to the situational needs, can enable the individual to better achieve their recovery goals. Trento, with its dedicated Crisis service and the active involvement of Peer Support Specialists ("ESP" in italian), exemplifies how an integrated, multidisciplinary territorial approach that values the role of the socio-family context can enhance the outcomes of acute psychopathological crises and user engagement. This article discusses the organisation, advantages, and challenges compared to intra-hospital management, and the impact this intervention can have on public stigma regarding mental health.