Diagnostic pathway of the biopsy-naïve patient suspected for prostate cancer: Real-life scenario when multiparametric Magnetic Resonance Imaging is not centralized.

INTRODUCTION: We aimed to compare the pathway including multi-parametric Magnetic Resonance Imaging (mpMRI) versus the one without mpMRI in detection of prostate cancer (PCa) when mpMRI is not centralized. MATERIALS: January 2019-March 2020: prospective data collection of trans-perineal prostate biopsies. Group A: biopsy-naïve patients who underwent mpMRI (at any institution) versus Group B: patients who did not. Within Group A, patients were stratified into those with negative mpMRI (mpMRI-, PIRADS v2.1=1-3, with PSA density <0.15 if PIRADS 3) who underwent standard biopsy (SB), versus those with positive mpMRI (mpMRI+, when PIRADS 3-5, with PSA density>0.15 if PIRADS 3) who underwent cognitive fusion biopsy. RESULTS: Two hundred and eighty one biopsies were analyzed. 153 patients underwent mpMRI (Group A). 98 mpMRI+ underwent fusion biopsy; 55 mpMRI- underwent SB. 128 Group B patients underwent SB. Overall PCa detection rate was 52.3% vs. 48.4% (Group A vs. B, P=0.5). Non-clinically-significant PCa was detected in 7.8 vs. 13.3% (Group A vs. B, P=0.1). Among the 98 mpMRI+ Group A patients only 2 had non clinically-significant disease. In 55 mpMRI- patients who underwent SB, 10 (18.2%) had clinically-significant PCa. Prostate volume predicted detection of PCa. In Group B, age and PSA predicted PCa. Sensitivity of mpMRI was 75.0% for all PCa, 85.3% for clinically-significant PCa. CONCLUSION: Higher detection of PCa and lower detection of non-clinically-significant PCa favored mpMRI pathway. A consistent number of clinically-significant PCa was diagnosed after a mpMRI-. Thus, in real-life scenario, mpMRI- does not obviate indication to biopsy when mpMRI is not centralized. LEVEL OF EVIDENCE: 3.

Modelling PAHs removal in activated sludge process: effect of disintegration.

The removal of polycyclic aromatic hydrocarbons (PAHs) in activated sludge was evaluated using two laboratory-scale bioreactors, coupled or not with a disintegration system (sonication). Mass balances performed on each system underlined that PAHs removal was significantly improved after sludge disintegration, especially for the higher molecular weight PAHs studied, which tended to adsorb to suspended matter. A model was developed in order to study the effect of sludge disintegration on the content of dissolved and colloidal matter (DCM), and to predict the potential impacts on PAHs availability and degradation. Results showed that this new model was efficient for capturing apparent degradation improvement trends and for discriminating between the involved mechanisms. This study showed that DCM content increased after sludge disintegration, and proved to be the main driver for improving PAHs apparent degradation.

The role of preoperative prostatic shape in the recovery of urinary continence after robotic radical prostatectomy: a single cohort analysis.

BACKGROUND: To explore the role of preoperative MRI prostate shape in urinary incontinence after robot-assisted radical prostatectomy (RARP). METHODS: Patients were stratified into four groups based on the mpMRI prostatic apex shape: Group A (prostatic apex overlapping the membranous urethra anteriorly and posteriorly), Group B and C (overlap of the prostatic apex of the anterior or posterior membranous urethra, respectively) and Group D (no overlap). Preoperative variables and intraoperative data were compared. Continence recovery was defined as no pad/day or 1 safety pad/day by an outpatient evaluation performed at 1, 3, 6, and 12 months after RARP. RESULTS: One hundred patients underwent RARP were classified as belonging to Group A (n = 30), Group B (n = 16), Group C (n = 14), and Group D (n = 40). Group D showed a significantly more favorable urinary continence recovery after RARP respect to all the other shapes presenting any forms of overlapping (HR = 1.9, 95% CI 1.2-3.1, p = 0.007). The estimated HR remained substantially unchanged after adjusting by age, body mass index, CCI, prostate volume, and bladder neck sparing (HR = 1.9, 95% CI 1.1-3.2, p = 0.016). The continence recovery median time was 9 months for Group A + B + C (95% CI 5-11) and 4 months for Group D (95% CI 2-6) (p = 0.023). CONCLUSION: Shape D showed a better continence recovery when compared to other shapes presenting any kind of overlapping of the prostatic apex over the membranous urethra.

Location and chemical composition of microbially induced phosphorus precipitates in anaerobic and aerobic granular sludge.

This work focuses on combined scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX) applied to granular sludge used for biological treatment of high-strength wastewater effluents. Mineral precipitation is shown to occur in the core of microbial granules under different operating conditions. Three dairy wastewater effluents, from three different upflow anaerobic sludge blanket (UASB) reactors and two aerobic granular sequenced batch reactors (GSBR) were evaluated. The relationship between the solid phase precipitation and the chemical composition of the wastewater was investigated with PHREEQC software (calculation of saturation indexes). Results showed that pH, Ca:P ratios and biological reactions played a major role in controlling the biomineralization phenomena. Thermodynamics calculations can be used to foresee the nature of bio-precipitates, but the location of the mineral concretions will need further investigation as it is certainly due to local microbial activity.

Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10-year period in South East England.

OBJECTIVE: The aims of the study were to determine how frequently oral potentially malignant disorders (OPMDs) transform to cancer and to identify clinical and histological factors determining the rates of transformation. METHODS: The study included 1357 patients with biopsy-confirmed OPMDs seen at Guy's Hospital between 1990 and 1999 and followed up until 2005. The patients' details (name, date of birth, gender and any other relevant information) were matched to the Thames Cancer Registry (TCR) database and Office for National Statistics (ONS) to identify patients who subsequently developed oral cancer (ICD-10 C00-C06). From each patient's record, we identified their highest grade of dysplasia, graded as none, mild, moderate or severe. The outcome of principal interest was transformation to oral squamous cell carcinoma. To avoid co-existing malignancies, follow-up was started 6 months after the date of the index biopsy. Kaplan-Meier estimates and Cox proportional hazard analysis were undertaken to explore the factors associated with the time to transformation to oral cancer. RESULTS: One thousand three hundred and fifty-seven patients were included in the study. The majority of patients were women (60.9%), and ∼30% were under 47 years of age. The most common OPMD was lichen planus/lichenoid reaction. Among all OPMDs, 204 (15.1%) had oral epithelial dysplasia (30 severe, 70 moderate and 104 mild). Thirty-five patients developed oral cancer over the follow-up period (2.6%). There was an association between dysplasia grade and time to transformation. Patients with severe dysplasia had a higher risk of transformation to oral cancer [HR 35.4 95% CI (14.2-88.3)] compared to those with no dysplasia. This association remained significant although attenuated [HR 21.6 95% CI (5.8-80.5)] following adjustment for sex, age, anatomical site of OPMD and diagnosis. A significant trend over dysplasia grades was evident (P < 0.0001). Transformation to oral cancer was also associated with increasing age (P = 0.0390). CONCLUSIONS: In 2.6% of cases, OPMDs transformed to invasive cancer for a total person follow-up time of 12,273 years (mean 9.04 years). The severity of dysplasia is a significant predictor for malignant transformation.

Multidetector computed tomographic coronary angiography as an alternative to conventional coronary angiography in non-coronary surgical patients.

AIM: Aim of our study was to evaluate multidetector 64-slice spiral computed tomography (MSCT) as an alternative to traditional coronary angiography (CA) to detect concomitant coronary artery disease (CAD) in patients initially admitted for non-coronary surgical procedures. METHODS: We have analyzed data of 380 consecutive patients operated from 2006 to 2008 initially admitted for aortic (N.=170) or mitral (N.=67) valve disease, ascending aorta aneurysm ± aortic valve disease (N.=99), and other (combined valve diseases, tumors; N.=44). These patients were submitted either to MSCT (Group CT, N.=112) or to CA (Group A, N.=268). Inclusion criteria to perform MSCT were no previous myocardial infarction or documented CAD, normal left ventricular function, sinus rhythm, less than 2-3 premature ventricular or atrial contractions /min. RESULTS: In Group CT, CAD was definitively excluded in 95 patients (85%) and was detected in 17; 8 of those 17 patients were subsequently submitted to CA and coronary artery bypass surgery for significant CAD. As compared to those in Group A, patients in Group CT were younger (64±15 vs. 70±10 years, P<0.0001), had less hypertension (P=0.0001), chest pain (P<0.05), peripheral vascular disease (P<0.05). NYHA class, incidence of diabetes, smoking habit, family history of CAD were similar. The incidence of operative mortality, postoperative myocardial infarction was not significantly different in both Group CT (0%) and A (0.4%) (P=NS). CONCLUSION: In selected cardiac surgical patients less invasive 64-slice MSCT can be with some limits an alternative to CA to rule out CAD, as confirmed by the absence of postoperative ischemic complications.

Evaluation with 64-slice CT of the prevalence of coronary artery variants and congenital anomalies: a retrospective study of 3,236 patients.

PURPOSE: This study retrospectively evaluated the prevalence of anatomical coronary artery variants and congenital anomalies in 3,236 patients imaged with 64-slice computed tomography (CT). MATERIALS AND METHODS: Over a period of 4 years, 3,236 patients underwent CT coronary angiography performed with the standard protocol. We assessed coronary artery dominance, presence of the intermediate branch, presence and number of diagonal and marginal branches and coronary anomalies subdivided into anomalies of origin and course, intrinsic anomalies and termination anomalies. RESULTS: Coronary dominance was right-sided in 88.1% of patients; the intermediate branch was present in 21.3%, the number of diagonal and marginal branches was one to two in >90%, and the number of coronary anomalies was 224 (89 of origin and course, 129 intrinsic anomalies and six termination anomalies). CONCLUSIONS: Sixty-four-slice CT coronary angiography provides accurate three-dimensional evaluation of the coronary artery tree with correct visualisation of any coronary anomalies, a relatively common finding that had a prevalence of 5.7% in our study population.

Anatomical and functional evaluation of the myocardium in patients with acute coronary syndrome (NSTEMI) using MR imaging.

PURPOSE: The aim of our study was to evaluate the role of magnetic resonance (MR) imaging in identifying the location and extent of acute ischaemic injury to predict reversibility and distinguish areas of acute from chronic ischaemia in patients with acute coronary syndrome non- ST-elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: We evaluated 22 patients with NSTEMI acute coronary syndrome confirmed by coronary angiography (CA). We studied ventricular function indices and segmental changes in wall thickness and kinetics by cine-MR imaging sequences. Subsequently, we evaluated myocardial wall oedema with T2-weighted black-blood short-tau inversion recovery turbo spin echo (T2 BB-STIRTSE) sequences and identified areas of myocardial necrosis using T1-weighted turbo field-echo inversion recovery (T1 TFE-IR) sequences after contrast material administration. RESULTS: The results obtained with the single sequences were as follows: T2 BB-STIR-TSE: 96.8% sensitivity, 100% specificity, 99.7% negative predictive value, 99.7% positive predictive value; T1 TFE-IR: 45.8% sensitivity, 96.9% specificity, 92.3% negative predictive value, 90.3% positive predictive value; systolic wall thickening: 87.5% sensitivity, 91.8% specificity, 98.7% negative predictive value, 50% positive predictive value, 91.4% accuracy. CONCLUSIONS: Our study suggests that the sequences used for evaluating oedema and assessing viability allow for precise localisation and differentiation of areas of acute and chronic ischaemia by quantifying the possible mismatch between ischaemia and necrosis.

PI-RADS score v.2 in predicting malignancy in patients undergoing 5α-reductase inhibitor therapy.

BACKGROUND: To investigate if the PI-RADS score represents an effective tool in detecting prostate cancer in patients treated with a 5α-reductase inhibitor (dutasteride) and to identify dedicated total serum PSA and PSA density thresholds. METHODS: Between April 2015 and March 2018, 75 patients under dutasteride treatment underwent multi-parametric magnetic resonance imaging (mpMRI) scans and US/MRI fusion prostate biopsy. Lesions were classified into two groups: Group 1 included PI-RADS 4 and 5 lesions, whilst Group 2 included PI-RADS 3-4-5 lesions. Lesions in groups 1 and 2 were further divided according to the patients' history of previous prostate biopsy. RESULTS: Ninety-seven lesions were detected. In PI-RADS 4-5 group, mpMRI showed a sensitivity of 78.0% and a specificity of 78.7%. The positive predictive value (PPV) was 79.6% and the negative predictive value (NPV) 77.1%. In PI-RADS 3-4-5 group, sensitivity was 100%, specificity 21.3%, PPV 57.5%, NPV 100%. In PI-RADS 4-5 biopsy-naive group sensitivity was 71.4%, specificity 75.0%. PPV 78.9% and NPV 66.7%. In PI-RADS 4-5 non-biopsy-naive group sensitivity was 82.8%, specificity 80.6%, PPV 80%, and NPV 83.3%. PI-RADS 3-4-5 biopsy-naive group showed sensitivity 100%, specificity 31.3%, PPV 65.6%, NPV 100%. PI-RADS 3-4-5 non-biopsy-naive group showed sensitivity 100%, specificity 16.1%, PPV 52.7%, and NPV 100%. ROC curve analysis indicated a serum total PSA threshold of 6 ng/ml (AUC: 0.71-95% confidence interval: 0.60-0.81) and a PSA density >0.22 (AUC: 0.70-95% confidence interval: 0.6-0.81) as optimal cut-offs for recommending prostate biopsy. CONCLUSIONS: In our experience the PI-RADS score proved to be sufficiently accurate in predicting prostate cancer in patients under dutasteride therapy.

Diagnostic accuracy of 64-slice CT in evaluating coronary artery bypass grafts and of the native coronary arteries.

PURPOSE: Our aim was to evaluate the accuracy, sensitivity and specificity of 64-slice multidetector computed tomography (MDCT) in the assessment of occlusions and stenoses of arterial and venous bypass grafts and disease progression in the native vessels distal to the graft, and to compare the results with those of conventional coronary angiography. MATERIALS AND METHODS: We enrolled 78 individuals (45 men, 33 women; mean age 59) and evaluated 213 bypass grafts using a 64-slice MDCT scanner. All patients underwent conventional coronary angiography with a mean time interval between the two examinations of 2 days. RESULTS: One patient was excluded due to arrhythmia during the examination. The 212 bypass grafts in the remaining 77 patients (98.7%) consisted of 115 (54%) venous grafts and 97 (46%) arterial grafts. In the 115 venous grafts, MDCT showed a sensitivity, specificity and accuracy of 100% in evaluating occluded grafts and a sensitivity of 94.4%, specificity of 98.4% and accuracy of 96.9% in evaluating significant stenoses. In evaluating occluded arterial grafts, sensitivity was 83.3%, specificity 100% and accuracy 98.9%, whereas in evaluating stenoses of arterial grafts, sensitivity was 100%, specificity 97.7% and accuracy 98%. CONCLUSIONS: Sensitivity, specificity and accuracy in evaluating native coronary vessels distal to the graft allow for a complete assessment of the surgical and native circulation. The examination appears therefore to be exhaustive in ruling out or confirming the presence of diseased vessels in the postoperative follow-up.

Role of 64-slice cardiac computed tomography in the evaluation of patients with non-ST-elevation acute coronary syndrome.

PURPOSE: This study was done to evaluate the feasibility, sensitivity and specificity of 64-slice computed tomography (CT) in identifying haemodynamically significant (>50%) coronary artery stenoses in patients with suspected acute coronary syndrome (ACS) by correlating the CT findings with the clinical event and data provided by conventional coronary angiography (CCA). MATERIALS AND METHODS: Sixty-four patients (38 men and 26 women; mean age 65 years; range+/-10 years) presenting to our hospital's emergency department with a clinical suspicion of ACS were studied with 64-slice CT followed by CCA within 24 h of arrival. RESULTS: Two patients (3.1%) were excluded from the analysis due to artefacts. Per-patient analysis in the remaining 62 patients identified 24 cases (38.7%) of negative CT findings (no stenoses or stenoses <50%), 35 cases of positive CT findings (56.4%) with identification of the culprit lesion, two cases in which the culprit lesion was not identified and one patient with unconfirmed stenosis. Sensitivity and specificity were 94.6% and 96%, respectively. Per-vessel analysis (186 vessels) revealed 17 non-evaluable vessels (9.1%) due to motion artefacts, 61 vessels (32.8%) with stenosis >50%, seven overestimated vessels (3.7%) due to extensive calcifications, three vessels (1.6%) with underestimated stenosis and 98 vessels (52.6%) without stenosis. Sensitivity and specificity were 95.3% and 93.3%, respectively. CONCLUSIONS: In this type of emergency, coronary CT angiography could lead to considerably lower healthcare costs by identifying patients without coronary disease and allowing immediate discharge without any need for further diagnostic procedures.

Modelling a full scale membrane bioreactor using Activated Sludge Model No.1: challenges and solutions.

A full-scale membrane bioreactor (1,600 m(3) d(-1)) was monitored for modelling purposes during the summer of 2006. A complete calibration of the ASM1 model is presented, in which the key points were the wastewater characterisation, the oxygen transfer and the biomass kinetics. Total BOD tests were not able to correctly estimate the biodegradable fraction of the wastewater. Therefore the wastewater fractionation was identified by adjusting the simulated sludge production rate to the measured value. MLVSS and MLSS were accurately predicted during both calibration and validation periods (20 and 30 days). Because the membranes were immerged in the aeration tank, the coarse bubble and fine bubble diffusion systems coexisted in the same tank. This allowed five different aeration combinations, depending whether the 2 systems were operating separately or simultaneously, and at low speed or high speed. The aeration control maintained low DO concentrations, allowing simultaneous nitrification and denitrification. This made it difficult to calibrate the oxygen transfer. The nitrogen removal kinetics were determined using maximum nitrification rate tests and an 8-hour intensive sampling campaign. Despite the challenges encountered, a calibrated set of parameters was identified for ASM1 that gave very satisfactory results for the calibration period. Matching simulated and measured data became more difficult during the validation period, mainly because the dominant aeration configuration had changed. However, the merit of this study is to be the first effort to simulate a full-scale MBR plant.

Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice.

BACKGROUND: Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed. METHODS: We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy. RESULTS: In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1(-/-) and ICAM-1(-/-) mice, but not in Mac-1(-/-) mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease. CONCLUSIONS: ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade.

Protein extraction from activated sludge: an analytical approach.

To investigate the efficiency of different methods on exopolymeric substance (EPS) extraction, mechanical and chemical treatments were applied on two activated sludges, regarding the yield of protein extraction as well as their compatibility with usual quantification methods. Mechanical disruption methods do not drastically affect protein measurements by both bicinchoninic acid (BCA) and modified Lowry methods. Chemical compounds such as cationic exchange resin and triton show high interference with modified Lowry method while the protein quantification by BCA method is not affected. In addition, inner sludge compounds were shown to interfere with both methods: BCA and modified Lowry measurement respectively overestimate and underestimate protein content. According to these data, BCA method was chosen in this study as the most appropriate protein quantification method in sludge extracts. Comparison of various extraction protocols, combining mechanical and/or chemical treatments, shows that efficiency can be increased by repeating the same method or by applying a prior mechanical treatment. Proteins are preferably extracted by triton treatments, indicating the importance of hydrophobic interactions linking proteins to the EPS matrix. The amount of extracted proteins reaches 182 and 148 mg eq.BSA g(-1)VSS using triton/triton and ultraturax/triton extractions, respectively. Protease activity/extracted protein ratios vary widely depending on extraction protocols. Protease seemed to be preferably extracted by ultrasound and triton treatments (150-220 U mg(-1)protein). This study underlines that the choice of a relevant coupled quantification/extraction method is of great importance for efficient EPS determination.

Simultaneous removal of N and P in a SBR with production of valuable compounds: application to concentrated wastewaters.

This article examines the optimisation of recovery of phosphorus and nitrogen (via struvite) in small treatment units for high strength wastewaters using biologically assisted precipitation. The particular focus was the synergetic effect between removal of orthophosphate and the biological reactions occurring during nitrogen removal. The most sensitive parameter influencing the phosphate solid forms (HAP, MAP) is pH. Sequencing batch mode helps maintain high gradients in ammonia concentration, which encourages struvite precipitation. Nitrification has a key effect on the precipitation, through its influence on pH and ammonia concentration, determining the remaining soluble phosphorus concentration. Denitrification and CO(2) stripping, by increasing pH also improve precipitation of phosphorus. Optimal operating conditions will therefore depend on the chosen strategy: thus nitrification may help to keep phosphorus in a soluble form (as needed in direct urine reuse), whereas if co-precipitation is desired in the biological reactor, nitrification should be controlled in relation with others processes responsible for pH increase.

Modelling PAH partitioning during sludge disintegration: The key role of dissolved and colloidal matter.

The partitioning between solids and the aqueous phase largely controls the fate of PAH compounds in biological treatment. The prediction of PAH sorption behaviour into activated sludge was investigated here. The suitability of a three-compartment model to describe partitioning in such a complex matrix was first evaluated by adding increasing quantities of dissolved and colloidal matter (DCM) (from 0 to 34.9% of the total matter). In a range of DCM concentrations varying from 0 to 1.4 g L-1, the PAH aqueous fraction, including both freely dissolved and sorbed to DCM molecules, increased from 9.9% to 33% for naphthalene (the most soluble PAH) and from 0.29% to 13.3% for indeno(1,2,3,c,d)pyrene (the least soluble PAH tested). The sorption of PAHs on dissolved and colloidal matter (DCM) was assessed by determining two partitioning constants (KPART and KDCM) for the 16 PAHs listed by the US EPA. New experiments were carried out for model validation and show that the model properly predicts the PAH partitioning following sludge disintegration by sonication.

Enrichment and adaptation yield high anammox conversion rates under low temperatures.

This study compared two anammox sequencing batch reactors (SBR) for one year. SBRconstantT was kept at 30 °C while temperature in SBRloweringT was decreased step-wise from 30 °C to 20 °C and 15 °C followed by over 140 days at 12.5 °C and 10 °C. High retention of anammox bacteria (AnAOB) and minimization of competition with AnAOB were key. 5-L anoxic reactors with the same inoculum were fed synthetic influent containing 25.9 mg NH4+-N/L and 34.1 mg NO2--N/L (no COD). Specific ammonium removal rates continuously increased in SBRconstantT, reaching 785 mg NH4+-N/gVSS/d, and were maintained in SBRloweringT, reaching 82.2 and 91.8 mg NH4+-N/gVSS/d at 12.5 and 10 °C respectively. AnAOB enrichment (increasing hzsA and 16S rDNA gene concentrations) and adaptation (shift from Ca. Brocadia to Ca. Kuenenia in SBRloweringT) contributed to these high rates. Rapidly settling granules developed, with average diameters of 1.2 (SBRconstantT) and 1.6 mm (SBRloweringT). Results reinforce the potential of anammox for mainstream applications.

Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX3CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.

Author Correction: Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

This article contains errors in Figs. 5 and 6, for which we apologize. In Fig. 5f, the image 'E12.5 tail' was inadvertently replaced with a duplicate of the image 'E12.5 trunk' from the same panel. In Figure 6d, the image 'E9.5/OH-TAM E8.5, embryo' was inadvertently replaced with a duplicate of the image 'E10.5/ OH-TAM E8.5, embryo' from Fig. 6b. The corrected versions of these figures appear in the Author Correction associated with this Article.

The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.

In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.