Artificial intelligence solution to accelerate the acquisition of MRI images: Impact on the therapeutic care in oncology in radiology and radiotherapy departments.

PURPOSE: MRI is essential in the management of brain tumours. However, long waiting times reduce patient accessibility. Reducing acquisition time could improve access but at the cost of spatial resolution and diagnostic quality. A commercially available artificial intelligence (AI) solution, SubtleMR™, can increase the resolution of acquired images. The objective of this prospective study was to evaluate the impact of this algorithm that halves the acquisition time on the detectability of brain lesions in radiology and radiotherapy. MATERIAL AND METHODS: The T1/T2 MRI of 33 patients with brain metastases or meningiomas were analysed. Images acquired quickly have a matrix divided by two which halves the acquisition time. The visual quality and lesion detectability of the AI images were evaluated by radiologists and radiation oncologist as well as pixel intensity and lesions size. RESULTS: The subjective quality of the image is lower for the AI images compared to the reference images. However, the analysis of lesion detectability shows a specificity of 1 and a sensitivity of 0.92 and 0.77 for radiology and radiotherapy respectively. Undetected lesions on the IA image are lesions with a diameter less than 4mm and statistically low average gadolinium-enhancement contrast. CONCLUSION: It is possible to reduce MRI acquisition times by half using the commercial algorithm to restore the characteristics of the image and obtain good specificity and sensitivity for lesions with a diameter greater than 4mm.

Development and numerical/experimental characterization of a lab-scale flat flame reactor allowing the analysis of pulverized solid fuel devolatilization and oxidation at high heating rates.

This paper deals with the thorough characterization of a new experimental test bench designed to study the devolatilization and oxidation of pulverized fuel particles in a wide range of operating conditions. This lab-scale facility is composed of a fuel feeding system, the functioning of which has been optimized by computational fluid dynamics. It allows delivering a constant and time-independent mass flow rate of fuel particles which are pneumatically transported to the central injector of a hybrid McKenna burner using a carrier gas stream that can be inert or oxidant depending on the targeted application. A premixed propane/air laminar flat flame stabilized on the porous part of the burner is used to generate the hot gases insuring the heating of the central coal/carrier-gas jet with a thermal gradient similar to those found in industrial combustors (>10(5) K/s). In the present work, results issued from numerical simulations performed a priori to characterize the velocity and temperature fields in the reaction chamber have been analyzed and confronted with experimental measurements carried out by coupling particle image velocimetry, thermocouple and two-color pyrometry measurements so as to validate the order of magnitude of the heating rate delivered by such a new test bench. Finally, the main features of the flat flame reactor we developed have been discussed with respect to those of another laboratory-scale system designed to study coal devolatilization at a high heating rate.

Integrated fixed-film activated sludge ANITA™Mox process--a new perspective for advanced nitrogen removal.

ANITA™Mox is a Veolia process using moving-bed biofilm reactor (MBBR) technology tested and validated in full-scale for energy- and cost-effective autotrophic N-removal from sidestream effluent using anammox (ANaerobic AMMonium OXidation) bacteria. In order to increase the ANITA™Mox process performances under different operating conditions (e.g. mainstream and sidestream application), substrate transport and accessibility inside the biofilm must be enhanced. In this work, (i) two laboratory scale biofilm ANITA™Mox reactors were operated using different configurations (IFAS - integrated fixed-film activated sludge - and MBBR) and (ii) the distribution of the anammox (AnAOB) and ammonia-oxidizing bacteria (AOB) in the suspended sludge and the biofilm was characterized using molecular tools (qPCR). This study showed that in IFAS configuration, the ANITA™Mox process achieved very high N-removal rate (up to 8 gN/m².d), which was three to four times higher than that achieved in the pure MBBR mode. The high concentration of suspended solids (mixed liquor suspended solids (MLSS)) in the bulk obtained within the IFAS mode induces a very efficient bacterial distribution between the AOB and AnAOB population. AnAOB activity mainly occurs in the biofilm (96% of total AnAOB in the reactor), whereas nitritation by AOB mostly takes place in the suspended phase (93% of total AOB). This spatial distribution observed in the IFAS reactor results from a natural selection due to more easily substrate accessibility for AOB in the bulk (NH4(+), O2) creating higher nitrite concentration in the bulk liquid compare to pure MBBR mode. The efficient control of MLSS level in the IFAS reactor is a key parameter to enhance the nitrite production by AOB and increase the substrate availability in the AnAOB-enriched biofilm leading to higher N-removal rate. These promising results obtained at laboratory scale have been further confirmed in on-going full-scale IFAS ANITA™Mox trials opening new roads for the widespread application of a very compact and robust ANITA™Mox process for sidestream but also mainstream cost-effective N-removal.

Experience from start-ups of the first ANITA Mox plants.

ANITA™ Mox is a new one-stage deammonification Moving-Bed Biofilm Reactor (MBBR) developed for partial nitrification to nitrite and autotrophic N-removal from N-rich effluents. This deammonification process offers many advantages such as dramatically reduced oxygen requirements, no chemical oxygen demand requirement, lower sludge production, no pre-treatment or requirement of chemicals and thereby being an energy and cost efficient nitrogen removal process. An innovative seeding strategy, the 'BioFarm concept', has been developed in order to decrease the start-up time of new ANITA Mox installations. New ANITA Mox installations are started with typically 3-15% of the added carriers being from the 'BioFarm', with already established anammox biofilm, the rest being new carriers. The first ANITA Mox plant, started up in 2010 at Sjölunda wastewater treatment plant (WWTP) in Malmö, Sweden, proved this seeding concept, reaching an ammonium removal rate of 1.2 kgN/m³ d and approximately 90% ammonia removal within 4 months from start-up. This first ANITA Mox plant is also the BioFarm used for forthcoming installations. Typical features of this first installation were low energy consumption, 1.5 kW/NH4-N-removed, low N2O emissions, <1% of the reduced nitrogen and a very stable and robust process towards variations in loads and process conditions. The second ANITA Mox plant, started up at Sundets WWTP in Växjö, Sweden, reached full capacity with more than 90% ammonia removal within 2 months from start-up. By applying a nitrogen loading strategy to the reactor that matches the capacity of the seeding carriers, more than 80% nitrogen removal could be obtained throughout the start-up period.

Modelling and simulation revealing mechanisms likely responsible for achieving the nitrite pathway through aeration control.

Nitrogen removal via nitrite has recently gained a lot of interest because it results in significant savings in both aeration costs and COD (chemical oxygen demand) requirements for denitrification, when compared to the conventional biological nitrogen removal via nitrate. The effectiveness of two different control strategies to achieve the nitrite pathway in systems with sludge retention has been experimentally demonstrated: (i) control of aerobic phase length, with which aeration is terminated as soon as ammonia is completely oxidised; (ii) operation at low DO setpoints in the aerobic phase. These strategies have been extensively studied in nitrifying reactors and are currently applied in real systems achieving biological carbon, nitrogen and phosphorus removal. In this work, we aim to demonstrate, through modelling and simulation, that the competition between nitrite reducers and nitrite oxidisers for nitrite, rather than kinetic selection plays a major role in NOB washout. Moreover, the results show that the occurrence of simultaneous nitrification and denitrification under "aerobic" conditions is very helpful for the nitrite pathway obtainment and for a more efficient COD utilisation.

A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis.

OBJECTIVE: Improved outcome measures in systemic sclerosis (SSc) are critical to finding active therapeutics for this disease. The modified Rodnan skin thickness score (MRSS) is the current standard for evaluating skin disease in SSc, but it is not commonly used in the clinical setting, in part because it requires specialized training to perform accurately and consistently. The purpose of this study was to investigate whether skin gene expression might serve as a more objective surrogate outcome measure to supplement skin score evaluations. METHODS: Skin RNAs from a group of patients with diffuse cutaneous SSc were studied for expression levels of genes known to be regulated by transforming growth factor beta (TGFbeta) and interferon (IFN). These levels were correlated with the MRSS, using multiple regression analyses to obtain best-fit models. RESULTS: Skin expression of the TGFbeta-regulated genes cartilage oligomeric matrix protein (COMP) and thrombospondin 1 (TSP-1) correlated moderately well with the MRSS, but the addition of other TGFbeta-regulated genes failed to significantly improve best-fit models. IFN-regulated genes were also found to correlate with the MRSS, and the addition of interferon-inducible 44 (IFI44) and sialoadhesin (Siglec-1) to COMP and TSP-1 in multiple regression analyses significantly improved best-fit models, achieving an R(2) value of 0.89. These results were validated using an independent group of skin biopsy samples. Longitudinal scores using this 4-gene biomarker indicated that it detects change over time that corresponds to changes in the MRSS. CONCLUSION: We describe a 4-gene predictor of the MRSS and validate its performance. This objective measure of skin disease could provide a strong surrogate outcome measure for patient care and for clinical trials.

Original use of a direct injection high efficiency nebulizer for the standardization of liquid fuels spray flames.

It is of practical importance to lead laboratory-scale experiments allowing a better understanding of the impact of commercial fuels composition on the formation of combustion residues such as soot particles. To this end, a hybrid burner has been designed recently to burn high-speed sprays of small liquid fuel droplets. It consists of a Holthuis (previously McKenna) burner originally equipped with a direct injection high efficiency nebulizer for the atomization of liquid hydrocarbons. A detailed description of this original setup is given in this paper. A priori estimations of atomization and evaporation times and length scales are then proposed and compared with experimental data. Droplet-size distribution measurements obtained in nonreacting conditions using a Malvern Spraytec particle sizer are presented and compared with values estimated by calculation. Cold sprays contours and liquid jet lengths in flames determined by Mie scattering at 532 and 1064 nm, respectively, are also presented. The results discussed in this work indicate that the hydrodynamic characteristics of the sprays generated with our system are relatively independent of the physical properties of fuels leading to comparable flames with identical liquid jet lengths, dimensions, and global structure. This feature facilitates an accurate comparison of flames burning various liquid hydrocarbons, which is of interest to emphasize differences in pollutants emissions and to highlight chemical effects for soot formation analysis.

Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor beta.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) accumulates in systemic sclerosis (SSc) skin and is upregulated by transforming growth factor (TGF)beta. To further characterise the response to TGFbeta in SSc, we investigated TGFbeta1 and COMP expression and myofibroblast staining in SSc skin. METHODS: Skin biopsies from patients with diffuse cutaneous SSc (dSSc), limited cutaneous SSc (lSSc) and healthy controls were evaluated for COMP mRNA expression using real-time PCR. COMP, alpha-smooth muscle actin (SMA) and TGFbeta were assessed in skin sections and in cultured fibroblasts by immunohistochemistry. Clinical disease status was assessed by the modified Rodnan skin score (mRSS). RESULTS: Myofibroblasts expressing SMA and COMP were found coexpressed in many cells in dSSc dermis, but each also stained distinct cells in the dermis. Cultured SSc dermal fibroblasts also showed heterogeneity for COMP and SMA expression, with cells expressing SMA, COMP, both or neither. TGFbeta treatment increased COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from patients with dSSc correlated with the mRSS and TGFbeta1 staining. CONCLUSION: These findings suggest that TGFbeta upregulation of COMP and/or SMA expression in subpopulations of fibroblasts contributes to different pathways of fibrosis and that multiple TGFbeta regulated genes may serve as biomarkers for the degree of SSc skin involvement.

Strategies for blood management in orthopaedic and trauma surgery.

Several aspects of the management of an orthopaedic surgical patient are not directly related to the surgical technique but are nevertheless essential for a successful outcome. Blood management is one of these. This paper considers the various strategies available for the management of blood loss in patients undergoing orthopaedic and trauma surgery.

MALDI imaging of formalin-fixed paraffin-embedded tissues: application to model animals of Parkinson disease for biomarker hunting.

A common technique for the long-term storage of tissues in hospitals and clinical laboratories is preservation in formalin-fixed paraffin-embedded (FFPE) blocks. Such tissues stored for more than five years have not been useful for proteomic studies focused on biomarker discovery. Recently, MS-based proteomic analyses of FFPE showed positive results on blocks stored for less than 2 days. However, most samples are stored for more than one year, and thus our objective was to establish a novel strategy using as a model system 6-hydroxydopamine (6-OHDA) treated rat brain tissues stored in FFPE blocks for more than 9 years. We examined MALDI tissue profiling combining the use of automatic spotting of the MALDI matrix with in situ tissue enzymatic digestion. On adjacent sections, the identification of compounds is carried out by tissue digestion followed by nanoLC/MS-MS analysis. The combination of these approaches provides MALDI direct analysis, MALDI/MS imaging, as well as the localization of a large number of proteins. This method is validated since the analyses confirmed that ubiquitin, trans-elongation factor 1, hexokinase, and the Neurofilament M are down-regulated as previously shown in human or Parkinson animal models. In contrast, peroxidoredoxin 6, F1 ATPase, and alpha-enolase are up-regulated. In addition, we uncovered three novel putative biomarkers, the trans-elongation factor 1 (eEF1) and the collapsin response mediator 1 and 2 from protein libraries. Finally, we validate the CRMP-2 protein using immunocytochemistry and MALDI imaging based on the different ions from trypsic digestion of the protein. The access to archived FFPE tissue using MALDI profiling and imaging opens a whole new area in clinical studies and biomarker discovery from hospital biopsy libraries.

Cysteine and serine proteases of synovial tissue in rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To compare the activities of cathepsin B (EC 3.4.22.1) and L (EC 3.4.22.15), calpain (EC 3.4.22.17), and dipeptidyl peptidase (EC 3.4.14.5 or DPP IV or CD26) in synovial membrane from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and post-traumatic joint injury (PT). METHODS: Forty RA patients were divided into two groups on the basis of surgical procedure: the RAs group comprised 18 patients requiring surgical synovectomy; the RAr group comprised 22 patients requiring a total joint replacement or arthrodesis. A third group (the OA group) comprised 19 OA patients while six patients with post-traumatic joint injury were included in the fourth group (the PT group). Cathepsin and calpain activity was assessed using a Cobas Fara II centrifugal analyser. DPP IV activity was determined kinetically using a fluorogenic substrate. RESULTS: RAs patients were significantly younger than RAr patients, and the mean duration of RA was shorter in the RAs group than in the RAr group. Cathepsin and calpain activity in synovial membrane was higher in RA and OA patients than in the control group, but no statistical difference was observed between RA and OA. However, cathepsin, calpain, and DPP IV synovial activity was significantly higher in the RAs group than in either the OA or the PT group. CONCLUSION: Our results show that proteinase activity tends to be higher in joints with early synovitis in RA, and suggest that these enzymes are not all involved at the same stage of the disease.

Tag-mass: specific molecular imaging of transcriptome and proteome by mass spectrometry based on photocleavable tag.

MALDI tissue imaging of tissues has become a promising technique for tracking biomarkers while determining their location and structural characterization. We have now developed specific targeting probes (oligonucleotides, antibodies), named Tag-Mass. This approach is based on probes modified with a photocleavable linker coupled with a tag cleaved and detected using mass spectrometry. Tag-Mass development is the key for a rapid, sensitive, and accurate approach to correlate levels of expression of different mRNA or proteins in diseases.

Direct analysis and MALDI imaging of formalin-fixed, paraffin-embedded tissue sections.

Formalin fixation, generally followed by paraffin embedding, is the standard and well-established processing method employed by pathologist. This treatment conserves and stabilizes biopsy samples for years. Analysis of FFPE tissues from biopsy libraries has been, so far, a challenge for proteomics biomarker studies. Herein, we present two methods for the direct analysis of formalin-fixed, paraffin-embedded (FFPE) tissues by MALDI-MS. The first is based on the use of a reactive matrix, 2,4-dinitrophenylhydrazine, useful for FFPE tissues stored less than 1 year. The second approach is applicable for all FFPE tissues regardless of conservation time. The strategy is based on in situ enzymatic digestion of the tissue section after paraffin removal. In situ digestion can be performed on a specific area of the tissue as well as on a very small area (microdigestion). Combining automated microdigestion of a predefined tissue array with either in situ extraction prior to classical nanoLC/MS-MS analysis or automated microspotting of MALDI matrix according to the same array allows the identification of both proteins by nanoLC-nanoESI and MALDI imaging. When adjacent tissue sections are used, it is, thus, possible to correlate protein identification and molecular imaging. These combined approaches, along with FFPE tissue analysis provide access to massive amounts of archived samples in the clinical pathology setting.

MALDI-MS direct tissue analysis of proteins: Improving signal sensitivity using organic treatments.

Direct tissue analysis using MALDI-MS allows the generation of profiles while maintaining the integrity of the tissue, displaying cellular localizations and avoiding tedious extraction and purification steps. However, lower spectral quality can result from direct tissue analysis due to variations in section thickness, the nature of the tissue, and the limited access to peptides/proteins due to high lipid content. To improve signal sensitivity, we have developed a tissue-washing procedure using organic solvents traditionally used for lipid extraction, i.e., CHCl3, hexane, toluene, acetone, and xylene. The increased detection for peptides/proteins (m/z 5000-30,000) is close to 40% with chloroform or xylene, and 25% with hexane, while also improving sample reproducibility for each solvent used in the present study. This strategy improved matrix cocrystallization with tissue peptides/proteins and more importantly with cytoplasmic proteins without delocalization. The extracted lipids were characterized by nanoESI-QqTOF/MS/MS using the precursor ion mode, lithium adducts, or both and were identified as phospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and lysophosphatidylinositol, confirming membrane lipid extraction from the tissues.

Solid ionic matrixes for direct tissue analysis and MALDI imaging.

Direct analysis of tissue by MALDI-MS allows the acquisition of its biomolecular profile while maintaining the integrity of the tissue, giving cellular localization, and avoiding tedious extraction and purification steps. However, direct tissue analysis generally leads to some extent to a lowered spectral quality due to variation in thickness, freezing tissue date, and nature of the tissue. We present here new technical developments for the direct tissue analysis of peptides with ionic liquid made of matrix mixtures (alpha-cyano-4-hydroxycinnamic acid (CHCA)/2-amino-4-methyl-5-nitropyridine and alpha-cyano-4-hydroxycinnamic acid/N,N-dimethylaniline (CHCA/DANI)). The properties of these direct tissue analysis matrixes, especially CHCA/aniline when compared to CHCA, 2,5-dihydroxybenzoic acid, and sinapinic acid, are as follows: (1) better spectral quality in terms of resolution, sensitivity, intensity, noise, number of compounds detected, and contaminant tolerance, (2) better crystallization on tissues, i.e., coverage capacity, homogeneity of crystallization, homogeneity of crystal sizes, and time of crystallization, (3) better analysis duration in term of vacuum stability, (4) better resistance to laser irradiation especially for high-frequency lasers, (5) better ionic yield in negative mode, and (6) enough fragmentation yield to use the PSD mode on sections to get structural information. Applied to MALDI imaging on a MALDI LIFT-TOF with a 50-Hz laser frequency, these ionic matrixes have allowed the realization of a new type of image in both polarities and reflector mode using the same tissue section. These results give a new outlook on peptide tissue profiling by MS, characterization of compounds from tissue slices, and MALDI-MS high-quality imaging.

A novel wastewater treatment process: simultaneous nitrification, denitrification and phosphorus removal.

Simultaneous nitrification and denitrification (SND) via the nitrite pathway and anaerobic-anoxic enhanced biological phosphorus removal (EBPR) are two processes that can significantly reduce the COD demand for nitrogen and phosphorus removal. The combination of these two processes has the potential of achieving simultaneous nitrogen and phosphorus removal with a minimal requirement for COD. A lab-scale sequencing batch reactor (SBR) was operated in alternating anaerobic-aerobic mode with a low dissolved oxygen concentration (DO, 0.5 mg/L) during the aerobic period, and was demonstrated to accomplish nitrification, denitrification and phosphorus removal. Under anaerobic conditions, COD was taken up and converted to polyhydroxyalkanoates (PHA), accompanied with phosphorus release. In the subsequent aerobic stage, PHA was oxidized and phosphorus was taken up to less than 0.5 mg/L at the end of the cycle. Ammonia was also oxidised during the aerobic period, but without accumulation of nitrite or nitrate in the system, indicating the occurrence of simultaneous nitrification and denitrification. However, off-gas analysis found that the final denitrification product was mainly nitrous oxide (N2O) not N2. Further experimental results demonstrated that nitrogen removal was via nitrite, not nitrate. These experiments also showed that denitrifying glycogen-accumulating organisms rather than denitrifying polyphosphate-accumulating organisms were responsible for the denitrification activity.

Anterior knee pain with a posterior-stabilized mobile-bearing knee prosthesis: the effect of femoral component design.

Femoropatellar problems have been reported with some designs of posterior-stabilized knee prostheses with fixed bearings; we report similar findings with a posterior-stabilized mobile-bearing prosthesis. A review of 184 patients (193 knees) who underwent placement of a Rotaglide (Corin, Cirencester, UK) posterior-stabilized prosthesis with patellar resurfacing showed that only 33 knees (17%) had complete absence of femoropatellar complaints after at least 1 year of follow-up evaluation. Femoropatellar grinding was noted in the other 160 knees; 65 were asymptomatic, 78 were mildly symptomatic, and 17 were severely symptomatic. Two patients refused secondary treatment; 15 underwent arthroscopic debridement. The only abnormal finding was intra-articular fibrosis surrounding the patellar implant. After arthroscopic debridement of the fibrosis, all patients reported immediate relief of their symptoms followed by recurrence within 6 to 9 months. Inappropriate trochlear design of the femoral implant appears to be the main determinant of femoropatellar problems in these patients. Encroachment on the trochlea by a broad intercondylar box with a sharp anterior edge appears detrimental to function irrespective of the presence or absence of bearing mobility.

Hyperextension trauma to the elbow: radiological and ultrasonographic evaluation in handball goalkeepers.

OBJECTIVE: To detect elbow lesions produced by hyperextension in 30 elite handball goalkeepers. METHODS: Conventional radiographs, stress radiographs, and ultrasound examination of both elbows were used. As a control group, 30 male volunteers from the general population within the same age group with no history of elbow injury were used. RESULTS: Radiographic findings in the goalkeepers were osteophyte formation in 67%, loose bodies in 5.5%, and periarticular calcification in 5.5%. Significantly greater differences in medial joint space opening between stressed and unstressed elbows were measured in both elbows than in the control group. Ultrasonographic findings showed thickening of the medial collateral ligament in 50%, thickening of the tricipital tendon in 11%, and signs of ulnar neuritis in 22%. An intra-articular effusion was found in 66% and small loose bodies in 33%. No significant differences were found between the dominant and non-dominant elbows at radiological and ultrasound examination. The findings in the control group were normal. CONCLUSIONS: The findings support the theory that repetitive hyperextension trauma to the elbow in handball goalkeepers results in pathological changes.

[Muscle injuries in athletes: pathogenesis, diagnosis and treatment]. / Les accidents musculaires chez le sportif: pathogénie, diagnostic et traitement.

All muscles can be injured during sports activities, certain specific muscles in the lower extremities are particularly vulnerable. The spectrum of these injuries is wide. Muscle strain injuries frequently involve polyarticular muscles which contain a high percentage of fast-twitch fibres (Type II). Disruption of muscle fibres occurs near the myotendinous junction. In most cases, the diagnosis can be based upon history and physical examination. Ultrasound and Magnetic Resonance Imaging can be useful to determine the severity of a specific injury. The treatment of these injuries is basically conservative; surgery is rarely indicated. Prevention of these injuries is currently still an important issue.