Using dispersion models at microscale to assess long-term air pollution in urban hot spots: A FAIRMODE joint intercomparison exercise for a case study in Antwerp.

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m2. Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations.

Supporting the improvement of air quality management practices: The "FAIRMODE pilot" activity.

This paper presents the first outcomes of the "FAIRMODE pilot" activity, aiming at improving the way in which air quality models are used in the frame of the European "Air Quality Directive". Member States may use modelling, combined with measurements, to "assess" current levels of air quality and estimate future air quality under different scenarios. In case of current and potential exceedances of the Directive limit values, it is also requested that they "plan" and implement emission reductions measures to avoid future exceedances. In both "assessment" and "planning", air quality models can and should be used; but to do so, the used modelling chain has to be fit-for-purpose and properly checked and verified. FAIRMODE has developed in the recent years a suite of methodologies and tools to check if emission inventories, model performance, source apportionment techniques and planning activities are fit-for-purpose. Within the "FAIRMODE pilot", these tools are used and tested by regional/local authorities, with the two-fold objective of improving management practices at regional/local scale, and providing valuable feedback to the FAIRMODE community. Results and lessons learnt from this activity are presented in this paper, as a showcase that can potentially benefit other authorities in charge of air quality assessment and planning.

Source apportionment to support air quality planning: Strengths and weaknesses of existing approaches.

Information on the origin of pollution constitutes an essential step of air quality management as it helps identifying measures to control air pollution. In this work, we review the most widely used source-apportionment methods for air quality management. Using theoretical and real-case datasets we study the differences among these methods and explain why they result in very different conclusions to support air quality planning. These differences are a consequence of the intrinsic assumptions that underpin the different methodologies and determine/limit their range of applicability. We show that ignoring their underlying assumptions is a risk for efficient/successful air quality management as these methods are sometimes used beyond their scope and range of applicability. The simplest approach based on increments (incremental approach) is often not suitable to support air quality planning. Contributions obtained through mass-transfer methods (receptor models or tagging approaches built in air quality models) are appropriate to support planning but only for specific pollutants. Impacts obtained via "brute-force" methods are the best suited but it is important to assess carefully their application range to make sure they reproduce correctly the prevailing chemical regimes.

Review of the quality of total mesorectal excision does not improve the prediction of outcome.

AIM: A fair to moderate concordance in grading of the total mesorectal excision (TME) surgical specimen by local pathologists and a central review panel has been observed in the PROCARE (Project on Cancer of the Rectum) project. The aim of the present study was to evaluate the difference, if any, in the accuracy of predicting the oncological outcome through TME grading by local pathologists or by the review panel. METHOD: The quality of the TME specimen was reviewed for 482 surgical specimens registered on a prospective database between 2006 and 2011. Patients with a Stage IV tumour, with unknown incidence date or without follow-up information were excluded, resulting in a study population of 383 patients. Quality assessment of the specimen was based on three grades including mesorectal resection (MRR), intramesorectal resection (IMR) and muscularis propria resection (MPR). Using univariable Cox regression models, local and review panel histopathological gradings of the quality of TME were assessed as predictors of local recurrence, distant metastasis and disease-free and overall survival. Differences in the predictions between local and review grading were determined. RESULTS: Resection planes were concordant in 215 (56.1%) specimens. Downgrading from MRR to MPR was noted in 23 (6.0%). There were no significant differences in the prediction error between the two models; local and central review TME grading predicted the outcome equally well. CONCLUSION: Any difference in grading of the TME specimen between local histopathologists and the review panel had no significant impact on the prediction of oncological outcome for this patient cohort. Grading of the quality of TME as reported by local histopathologists can therefore be used for outcome analysis. Quality control of TME grading is not warranted provided the histopathologist is adequately trained.

Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis.

INTRODUCTION: Microscopic bowel inflammation is present in up to 50% of patients with spondyloarthritis (SpA) and is associated with more severe disease. Currently no reliable biomarkers exist to identify patients at risk. Calprotectin is a sensitive marker of neutrophilic inflammation, measurable in serum and stool. OBJECTIVES: To assess whether serum and faecal calprotectin in addition to C-reactive protein (CRP) can be used to identify patients with SpA at risk of microscopic bowel inflammation. METHODS: Serum calprotectin and CRP were measured in 125 patients with SpA. In 44 of these patients, faecal samples were available for calprotectin measurement. All 125 patients underwent an ileocolonoscopy to assess the presence of microscopic bowel inflammation. RESULTS: Microscopic bowel inflammation was present in 53 (42.4%) patients with SpA. Elevated serum calprotectin and CRP were independently associated with microscopic bowel inflammation. Faecal calprotectin was also significantly higher in patients with microscopic bowel inflammation. Patients with CRP and serum calprotectin elevated had a frequency of bowel inflammation of 64% vs 25% in patients with low levels of both. When either CRP or serum calprotectin was elevated, the risk was intermediate (40%) and measuring faecal calprotectin provided further differentiation. Hence we suggest a screening approach where initially serum calprotectin and CRP are assessed and, if necessary, faecal calprotectin. The model using this scenario provided an area under the ROC curve of 74.4% for detection of bowel inflammation. CONCLUSIONS: Calprotectin measurements in stool and serum, in addition to CRP, may provide a promising strategy to identify patients with SpA at risk of bowel inflammation and could play a role in overall patient stratification.

[Subcutaneous nodules of the head and neck heralding giant cell arteritis]. / Nodules sous-cutanés cervico-céphaliques précédant l'apparition d'une artérite à cellules géantes.

BACKGROUND: Giant cell arteritis is the most common form of systemic vasculitis affecting individuals aged over 50 years. While its clinical manifestations are numerous, cutaneous involvement is uncommon and rarely constitutes the initial sign. We discuss a case of atypical skin involvement as the initial symptom of giant cell arteritis. OBSERVATION: An 86-year-old woman presented purplish and painful subcutaneous nodules on the scalp and neck. Biological explorations showed systemic inflammation. The skin biopsy was evocative of polyarteritis nodosa. The nodules spontaneously disappeared completely, and asthenia and bitemporal headache gradually appeared. In view of the persistent inflammatory syndrome, a diagnosis of giant cell arteritis was proposed and was later confirmed by the temporal artery biopsy sample, with its typical histological appearance. Systemic corticosteroids resulted in complete regression of symptoms within a few days. DISCUSSION: To our knowledge, inflammatory cervical subcutaneous nodules have never been described in giant cell arteritis. The case we report herein thus raises the issue of differential diagnosis between various forms of vasculitis. While classification of the latter continues to progress thanks to improvements in physiopathological knowledge, the distinction between vasculitis of the large and small vessels remains tenuous on occasion. We discuss the differential diagnoses. CONCLUSION: The dermatological presentation of giant cell arteritis in the present case suggests the existence of a continuum between small-, medium- and large-vessel vasculitis.

Need for objective and reproducible criteria in histopathological assessment of total mesorectal excision specimens: lessons from a national improvement project.

AIM: Data on quality control of the pathologic evaluation of total mesorectal excision (TME) specimens are scarce. We aimed to assess differences between evaluation by local pathologists participating in PROject on CAncer of the REctum (PROCARE; a Belgian improvement project on rectal cancer) and by a review panel of experts. METHOD: Based on photographic material and histopathology slides, a Review Committee of gastrointestinal expert pathologists re-evaluated the mesorectal plane, the tumour differentiation grade, the (y)pT stage and the tumour regression grade in 444 patients previously routinely assessed by local pathologists. RESULTS: The surgical plane was reported in 89% of patients and the circumferential resection margin in 88% of patients by the local pathologist. The median number of lymph nodes harvested in patients undergoing neoadjuvant radiochemotherapy was 11 and 14 in the other patients. The Review Committee downgraded the surgical plane from (intra)mesorectal to intramuscular in 17% of patients, and upgraded it from intramuscular to (intra)mesorectal in 27%. Tumour differentiation grade, T stage and tumour regression grade differed between local pathologists and the Review Committee in 15%, 10% and 38%, respectively, of patients. T stage was upgraded, mainly from T2 to T3, in 8% of patients. Tumour regression was judged by the Review Committee to be less advanced in 15% of patients. CONCLUSION: Acknowledging some shortcomings, this study gives a realistic view of clinical practice. There are differences in interpretation with regard to both macroscopic and microscopic analysis of TME specimens. These findings indicate a need for more objective and reproducible criteria in histopathology. Being aware of this is a first step for improvement.

The UEMS section/board of pathology, chapter 6: requirement for recognition of postgraduate training in pathology: a presentation of the paris document.

After more than five years discussion the UEMS Section/Board of Pathology agreed a specification of requirements for recognition of post-graduate training in pathology, which is the key to the future of our discipline. The document published here, subject to ratification by UEMS Council, was voted on and accepted by the Pathology Board at the UEMS Paris meeting of 9 June 2012. Cytopathology is regarded as integral part of pathology: in general, training in pathology takes five years and maintains a common trunk of four (minimum three) years where surgical pathology, autopsy pathology and basic knowledge of neuropathology, dermatopathology and cytopathology are adequately trained and assessed. Training in so-called 'areas of interests' covers the remaining 12-24 months. Certificates of 'advanced level of competence' remain within the authority of national boards. As senior members of its Executive Board, we believe that the European Federation of Cytology Societies (EFCS) should take responsibility for establishing 1) standards in the quality of cytopathology training, 2) training guidelines and qualification for advanced levels of competence in cytopathology, 3) manpower planning, 4) tutorials for pathologists and cytotechnologists and 4) standards of cytotechnologist training.

Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolising enzyme that induces immune tolerance by modulating T-cell responses. Carcinomas may create an immunosuppressive state via IDO1 expression. Here we examined a possible contribution of IDO1 on this phenomenon and investigated whether IDO1 has prognostic value in colorectal cancer (CRC). METHODS: IDO1 expression was investigated by quantitative PCR and western blotting in three colon cancer cell lines, in basal state and after interferon (IFN)-γ stimulation. Semi-quantitative immunohistochemistry was used to evaluate IDO1 expression in 265 pT1-4N0-2Mx-staged CRCs. Results were related to clinical variables and correlated with amounts of CD3(+) and CD8(+) T lymphocytes, which were quantitatively evaluated using image analysis. RESULTS: In vitro expression of IDO1 depended on IFN-γ stimulation. Higher IDO1 expression at the tumour invasion front was an independent adverse prognostic factor in pT1-4N1Mx-staged CRC. It was associated with overall survival (P=0.001) and with metachronous metastases (P=0.018). IDO1 expression was not associated with the presence of CD3(+) or CD8(+) T lymphocytes. CONCLUSION: Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC.

Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype.

BACKGROUND: Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. OBJECTIVE: To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. METHODS: Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. RESULTS: Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. CONCLUSION: A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.

Aberrant spindle structures responsible for recurrent human metaphase I oocyte arrest with attempts to induce meiosis artificially.

BACKGROUND In some couples, not all retrieved oocytes mature, even after prolonged in vitro culture. The underlying mechanisms are not known, although ionophore treatment may alleviate metaphase I (MI) arrest in some mouse strains. We attempted to induce first polar body (PB) extrusion and fertilization using assisted oocyte activation (AOA) after ICSI in maturation-resistant human MI oocytes. METHODS Four ICSI patients are described in this retrospective study. A pilot study tested the calcium ionophore ionomycin (10 µM) on donated MI oocytes from patients with a normal number of metaphase II (MII) oocytes. Subsequently, ionomycin was used to induce first PB extrusion in two patients showing maturation-resistant MI oocytes. AOA, by calcium injection and ionomycin exposure, was applied when mature oocytes were available. Oocytes were analysed by polarized microscopy and immunostaining. RESULTS Ionomycin induced the first PB extrusion in MI oocytes from patients with a normal number of retrieved MII oocytes, while extended in vitro culture failed to achieve the MII stage. Similarly, ionomycin induced first PB extrusion in one of two patients with recurrent maturation-resistant MI oocytes. Use of ICSI combined with AOA on MII oocytes matured in vitro or in vivo resulted in failed or abnormal fertilization with no further embryo cleavage potential. Highly abnormal spindle and chromosome configurations were observed in MI maturation-resistant oocytes, in contrast to control MI oocytes. CONCLUSIONS Ionophore induced first PB extrusion in MI oocytes from patients without maturation arrest but to a lower extent in maturation-resistant MI oocytes. Immunofluorescence staining and confocal analysis revealed, for the first time, highly abnormal spindle/chromosomal structures that may be responsible for this maturation arrest.

Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle.

BACKGROUND: Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients. METHODS: We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B- versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed. RESULTS: Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B- than K-site (P < 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P < 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P < 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P = 0.0084), formation of larger antral follicles (P = 0.005), more metaphase-II (MII) oocytes, growing follicles (P = 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day. CONCLUSIONS: To our knowledge, this is the first report of MII and IVM-MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation.

Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis.

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder. Systemic treatment of IBD patients with anti-tumor necrosis factor (TNF)-alpha antibodies has proven to be a highly promising approach, but several drawbacks remain, including side effects related to systemic administration and high cost of treatment. Lactococcus lactis was engineered to secrete monovalent and bivalent murine (m)TNF-neutralizing Nanobodies as therapeutic proteins. These therapeutic proteins are derived from fragments of heavy-chain camelid antibodies and are more stable than conventional antibodies. L. lactis-secreted anti-mTNF Nanobodies neutralized mTNF in vitro. Daily oral administration of Nanobody-secreting L. lactis resulted in local delivery of anti-mTNF Nanobodies at the colon and significantly reduced inflammation in mice with dextran sulfate sodium (DSS)-induced chronic colitis. In addition, this approach was also successful in improving established enterocolitis in interleukin 10 (IL10)(-/-) mice. Finally, L. lactis-secreted anti-mTNF Nanobodies did not interfere with systemic Salmonella infection in colitic IL10(-/-) mice.In conclusion, this report details a new therapeutic approach for treatment of chronic colitis, involving in situ secretion of anti-mTNF Nanobodies by orally administered L. lactis bacteria. Therapeutic application of these engineered bacteria could eventually lead to more effective and safer management of IBD in humans.

Group C streptococcal psoas abscess associated with a homolateral hip joint prosthesis infection: a case report.

An abscess in the psoas muscle is rare and frequently misdiagnosed. A delay in the diagnosis can increase its mortality rate. Some clinical signs can help the clinician but they all are not always present, and not at the same time. We describe in this paper a case report of an association between a psoas abscess and a homolateral hip joint prosthesis infection. It was suspected because of no improvement in clinical state despite treatment of the abscess by antibiotics and drainage, and it required finally other complementary therapeutic solutions. The pathogenic microorganism was a group C streptococcus. We discuss all these points and thereafter we suggest some recommendations for the clinician.

Otitis media microbes: culture, PCR, and confocal laser scanning microscopy.

OBJECTIVES: To assess the presence of middle ear pathogens in nasopharynx (NP), middle ear fluid (MEF), and middle ear mucosal swabs (MES) of 14 patients undergoing middle ear surgery. METHODOLOGY: Bacteria were assessed by culture and species specific PCR. Biofilm was investigated by confocal laser scanning microscopy (CLSM) of middle ear biopsies (MEBs). RESULTS: Bacteria were absent in CLSM of MEBs in three of the four closed and healthy middle ears. Bacteria occurred in the ear with a foreign body (middle ear prosthesis), which showed localized living and dead bacteria, indicating biofilm. Bacterial growth was present in ten patient ears, but biofilm occurred in only one patient. CLSM indicated biofilm in the middle ear of two patients for whom PCR detected Haemophilus influenzae in the MEF. The three classical pathogens could frequently be found in the nasopharynx, by culture and PCR, but not from the middle ear. Alloiococcus otitidis was detected in the MEF of all five patients with open inflamed ears, though virtually absent from the nasopharynx. Pseudomonas aeruginosa was present in seven. It was the only pathogen found on several occasions in all three locations in one patient. CONCLUSIONS: This study confirms the association of H. influenzae with middle ear biofilm, and indicates a potential role of P. aeruginosa in middle ear inflammation and biofilm formation. Biofilm does not seem to cause inflammation. It is unclear whether the predominance of A. otitidis in chronically inflamed open middle ears indicates a pathogenic or contaminant role for this organism.

Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men.

BACKGROUND: In mammals, oocyte activation at fertilization is thought to be induced by the sperm-specific phospholipase C zeta (PLCzeta). However, it still remains to be conclusively shown that PLCzeta is the endogenous agent of oocyte activation. Some types of human infertility appear to be caused by failure of the sperm to activate and this may be due to specific defects in PLCzeta. METHODS AND RESULTS: Immunofluorescence studies showed PLCzeta to be localized in the equatorial region of sperm from fertile men, but sperm deficient in oocyte activation exhibited no specific signal in this same region. Immunoblot analysis revealed reduced amounts of PLCzeta in sperm from infertile men, and in some cases, the presence of an abnormally low molecular weight form of PLCzeta. In one non-globozoospermic case, DNA analysis identified a point mutation in the PLCzeta gene that leads to a significant amino acid change in the catalytic region of the protein. Structural modelling suggested that this defect may have important effects upon the structure and function of the PLCzeta protein. cRNA corresponding to mutant PLCzeta failed to induce calcium oscillations when microinjected into mouse oocytes. Injection of infertile human sperm into mouse oocytes failed to activate the oocyte or trigger calcium oscillations. Injection of such infertile sperm followed by two calcium pulses, induced by assisted oocyte activation, activated the oocytes without inducing the typical pattern of calcium oscillations. CONCLUSIONS: Our findings illustrate the importance of PLCzeta during fertilization and suggest that mutant forms of PLCzeta may underlie certain types of human male infertility.

Belgian consensus guidelines for follow-up of women with cervical cytological abnormalities.

In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required.As this represents an important cost in medical health care and has serious consequences for the affected women, it is important to have uniform and clear guidelines to allow an optimal follow-up and clinical management. A system for the uniform reporting of cervical cytology has been designed by the National Cancer Institute (U.S.A.) and resulted in the Bethesda System 1991. The present paper and the terminology used are based on the Bethesda System revised in 2001. It explains the guidelines, based on the 2001 Bethesda System and the 2004 consensus guidelines for the management of women with cervical cytological abnormalities, as developed by the members of the Board of the Belgian Society of Clinical Cytology, and adapted to the Belgian situation.