Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis.

OBJECTIVES: B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy. METHODS: We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by in vitro modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and in vitro assays. RESULTS: Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. In vitro modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF in vitro. CONCLUSIONS: Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.

Effect of surface treatment strategies on bond strength of additively and subtractively manufactured hybrid materials for permanent crowns.

OBJECTIVES: The purpose of this study is to evaluate the bond strength of different computer-aided design / computer-aided manufacturing (CAD/CAM) hybrid ceramic materials following different pretreatments. METHODS: A total of 306 CAD/CAM hybrid material specimens were manufactured, n = 102 for each material (VarseoSmile Crownplus [VSCP] by 3D-printing; Vita Enamic [VE] and Grandio Blocs [GB] by milling). Each material was randomly divided into six groups regarding different pretreatment strategies: control, silane, sandblasting (50 µm aluminum oxide particles), sandblasting + silane, etching (9% hydrofluorics acid), etching + silane. Subsequently, surface roughness (Ra) values, surface free energy (SFE) were measured. Each specimen was bonded with a dual-cured adhesive composite. Half of the specimens were subjected to thermocycling (5000 cycles, 5-55 °C). The shear bond strength (SBS) test was performed. Data were analyzed by using a two-way analysis of variance, independent t-test, and Mann-Whitney-U-test (α = 0.05). RESULTS: Material type (p = 0.001), pretreatment strategy (p < 0.001), and the interaction (p < 0.001) all had significant effects on Ra value. However, only etching on VSCP and VE surface increased SFE value significantly. Regarding SBS value, no significant difference was found among the three materials (p = 0.937), while the pretreatment strategy significantly influenced SBS (p < 0.05). Etching on VSCP specimens showed the lowest mean value among all groups, while sandblasting and silane result in higher SBS for all test materials. CONCLUSIONS: The bond strength of CAD/CAM hybrid ceramic materials for milling and 3D-printing was comparable. Sandblasting and silane coupling were suitable for both millable and printable materials, while hydrofluoric etching should not be recommended for CAD/CAM hybrid ceramic materials. CLINICAL RELEVANCE: Since comparable evidence between 3D-printable and millable CAD/CAM dental hybrid materials is scarce, the present study gives clear guidance for pretreatment planning on different materials.

Mechanical properties of 3D-printed and milled composite resins for definitive restorations: An in vitro comparison of initial strength and fatigue behavior.

OBJECTIVE: To evaluate the flexural strength and fatigue behavior of a novel 3D-printed composite resin for definitive restorations. MATERIALS AND METHODS: Fifty disc-shaped specimens were manufactured from each of a nanohybrid composite resin (NHC), polymer-infiltrated ceramic network (PICN), and 3D-printed composite resin (3D) with CAD-CAM technology. Biaxial flexural strength (σin ) (n = 30 per group) and biaxial flexural fatigue strength (σff ) (n = 20 per group) were measured using piston-on-three-balls method, employing a staircase approach of 105 cycles. Weibull statistics, relative-strength degradation calculations, and fractography were performed. The results were analyzed with 1-way ANOVA and Games-Howell post hoc test (α = 0.05). RESULTS: Significant differences in σin and σff among the groups (p < 0.001) were detected. The NHC group provided the highest mean ± standard deviation σin and σff (237.3 ± 31.6 MPa and 141.3 ± 3.8 MPa), followed by the PICN (140.3 ± 12.9 MPa and 73.5 ± 9.9 MPa) and the 3D (83.6 ± 18.5 MPa and 37.4 ± 23.8 MPa) groups. The 3D group exhibited significantly lower Weibull modulus (m = 4.7) and up to 15% higher relative strength degradation with areas of nonhomogeneous microstructure as possible fracture origins. CONCLUSIONS: The 3D-printed composite resin exhibited the lowest mechanical properties, where areas of nonhomogeneous microstructure developed during the mixing procedure served as potential fracture origins. CLINICAL SIGNIFICANCE: The clinical indications of the investigated novel 3D-printed composite resin should be limited to long-term provisional restorations. A cautious procedure for mixing the components is crucial before the 3D-printing process, since nonhomogeneous areas developed during the mixing could act as fracture origins.

Segmentation of process-related contaminations on two-piece abutments using pixel-based machine learning: a new quantification approach?

PURPOSE: A reference method for quantifying contaminations on two-piece abutments manufactured using CAD/CAM has not yet been established. In the present in vitro study, a pixel--based machine learning (ML) method for detecting contamination on customized two-piece abutments was investigated and embedded in a semiautomated quantification pipeline. MATERIALS AND METHODS: Forty-nine CAD/CAM zirconia abutments were fabricated and bonded to a prefabricated titanium base. All samples were analyzed for contamination by scanning electron microscopy (SEM) imaging followed by pixel--based ML and thresholding (SW) for contamination detection; quantification was performed in the postprocessing pipeline. Wilcoxon signed-rank test and Bland-Altmann plot were applied to compare both methods. The contaminated area fraction was recorded as a percentage. RESULTS: There was no statistically significant difference between the percentages of contamination areas (median = 0.004) measured with ML (median = 0.008) and with SW (median = 0.012), asymptotic Wilcoxon test: P = 0.22. The Bland-Altmann plot demonstrated a mean difference of -0.006% (95% confidence interval [CI] from -0.011% to 0.0001%) with increased values from a contamination area fraction of > 0.03% for ML. CONCLUSION: Both segmentation methods showed comparable results in evaluating surface cleanliness; pixel-based ML is a promising assessment tool for detecting external contaminations on zirconia abutments. Further studies are required to investigate the clinical performance of this tool.

Survival and complications of 3D-printed, non-invasive restorations for prosthetic rehabilitations: A 12-month preliminary observational study.

AIM: The adjustment and transfer of a stable occlusion can be a major challenge in prosthetic rehabilitations. The aim of this study was to assess a non-invasive treatment option for complex prosthetic rehabilitations and occlusal analyses using 3D-printed restorations clinically. MATERIALS AND METHODS: Eleven patients received a partial or complete rehabilitation with the aid of 3D-printed restorations (n=171). After 12 months of clinical service, all restorations were analyzed using the United States Public Health Service (USPHS) criteria. RESULTS: The 12-month clinical data revealed that 3D-printed restorations showed a survival rate of 84.4%. Complications occurred mostly regarding the anatomical form (7%) or marginal integrity (6AC%) and were consequently rated "Charlie" or "Delta." Color stability and color match of 3D-printed restorations were rated "Alpha" in 83% and 73%, respectively, of all restorations. Marginal inflammation was rated "Alpha" in 89% of all restorations. An excellent surface texture and no secondary caries or postoperative sensitivities (100%) were observed. CONCLUSIONS: 3D-printed restorations might be an alternative treatment option for initiating complex prosthetic rehabilitations. Technical complications rarely occurred. Biological complications did not occur at all. The color stability showed promising results after 12 months of clinical service. However, the results should be interpreted with caution. Long-term results with a high number of restorations should be awaited.

Background clutter amplitude and frequency of GPR signals to analyse water content in sedimentary deposits: Urban infrastructure environment.

Soil site studies are crucial in the analysis of seismic hazard in populated areas. This study focusses on the use of the Ground Penetrating Radar as a non-destructive geophysical method to analysis the water content of a sedimentary basin of a local urban area in Cervantes Parks in Barcelona city. Main objective of this work is to understand further the local seismic soil site, and analysis the background clutter amplitude and frequency of the GPR signal applied on the seasonal changes of the underground water content. Changes produces in the GPR signal could be associated to the changes of the ground material due to the existence of water content and water flow, which influence the grain size distribution of the soil characterisation. Previously, several methodologies have been applied to determine the changes of the ground material due to the existence of water content and most importantly effect of the seasonal changes on the soil characterisation. GPR has been applied as a new technology and non-invasive to further analysis water content in shallow geology. Methodology applied on this study compromised in four different phases; Two seasonal data collection using 100 MHz centre frequency shielded antenna in both dry and wet season, radar images are proceeded with common post-processing approaches, following more innovative processing approach based on the Fast Fourier Transform (FFT) method in order to analysis background clutter amplitude and frequency spectrum to achieve an accurate interpretation of underground water content activities, in conclusion a comparative study of the results driven from radar images are elaborated considering historical knowledge. Results show that GPR is an efficient technique to analysis water content invasively considering low frequency antennas to achieve deeper penetration depth in sedimentary deposits, and predict shifting and increasing of the underground streams due to changes in weather conditions. Results could contribute to the enhancing local seismic site behaviour in populated areas considering continuous monitoring of underground water activities in sedimentary basin sites.

Definition of Optimized Indicators from Sensors Data for Damage Detection of Instrumented Roadways.

Pavement instrumentation sensors have become a common practice for structural monitoring. Data processing often consists of extracting different values generally representative of variations in the whole pavement, but this makes it more difficult to follow a specific characteristic of the structure. To overcome this limitation, this paper aimed to transpose an original method, labeled the Optimized Indicators Method (OIM), which consists of finding some weighting functions of a signal to evaluate some indicators linked to a physical characteristic of the structure. The main advantage of this method is that the inferred indicators are particularly sensitive to a specific characteristic of the structure without being sensitive to the others. This research work consisted of analyzing, conventionally and with the OIM, the signals of strain gauges, which were recorded during an experimental campaign carried out on a circular instrumented pavement and submitted to an accelerated fatigue testing. The OIM, calibrated through an experimental reference signal, makes it possible to evaluate independently, through weighting functions, some specific physical characteristics of the pavement. It showed a two-stepped degradation, starting with a damaging of the bituminous layer, followed by an alteration of the base layer, which could not be easily deduced from a conventional processing method.

In Vivo Analysis of the Regeneration Capacity and Immune Response to Xenogeneic and Synthetic Bone Substitute Materials.

Although various studies have investigated differences in the tissue reaction pattern to synthetic and xenogeneic bone substitute materials (BSMs), a lack of knowledge exists regarding the classification of both materials based on the DIN ISO 10993-6 scoring system, as well as the histomorphometrical measurement of macrophage subtypes within their implantation beds. Thus, the present study was conducted to analyze in vivo responses to both xenogeneic and synthetic bone substitute granules. A standardized calvaria implantation model in Wistar rats, in combination with established scoring, histological, histopathological, and histomorphometrical methods, was conducted to analyze the influence of both biomaterials on bone regeneration and the immune response. The results showed that the application of the synthetic BSM maxresorb® induced a higher pro-inflammatory tissue response, while the xenogeneic BSM cerabone® induced a higher anti-inflammatory reaction. Additionally, comparable bone regeneration amounts were found in both study groups. Histopathological scoring revealed that the synthetic BSM exhibited non-irritant scores at all timepoints using the xenogeneic BSM as control. Overall, the results demonstrated the biocompatibility of synthetic BSM maxresorb® and support the conclusion that this material class is a suitable alternative to natural BSM, such as the analyzed xenogeneic material cerabone®, for a broad range of indications.

DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy.

The muscle-specific RING-finger protein MuRF1 (also known as TRIM63) constitutes a bona fide ubiquitin ligase that routes proteins like several different myosin heavy chain proteins (MyHC) to proteasomal degradation during muscle atrophy. In two unbiased screens, we identified DCAF8 as a new MuRF1-binding partner. MuRF1 physically interacts with DCAF8 and both proteins localize to overlapping structures in muscle cells. Importantly, similar to what is seen for MuRF1, DCAF8 levels increase during atrophy, and the downregulation of either protein substantially impedes muscle wasting and MyHC degradation in C2C12 myotubes, a model system for muscle differentiation and atrophy. DCAF proteins typically serve as substrate receptors for cullin 4-type (Cul4) ubiquitin ligases (CRL), and we demonstrate that DCAF8 and MuRF1 associate with the subunits of such a protein complex. Because genetic downregulation of DCAF8 and inhibition of cullin activity also impair myotube atrophy in C2C12 cells, our data imply that the DCAF8 promotes muscle wasting by targeting proteins like MyHC as an integral substrate receptor of a Cul4A-containing ring ubiquitin ligase complex (CRL4A).This article has an associated First Person interview with the first author of the paper.

Level of Tumor Necrosis Factor Production by Stimulated Blood Mononuclear Cells Can Be Used to Predict Response of Patients With Inflammatory Bowel Diseases to Infliximab.

BACKGROUND & AIMS: A substantial proportion patients with inflammatory bowel disease (IBD) have a primary non-response to infliximab; markers are needed to identify patients most likely to respond to treatment. We investigated whether production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMCs) can be used as a marker to predict response. METHODS: We performed a prospective study of 41 adults with IBD (mean age, 38 years; 21 male; 21 with Crohn's disease and 20 with ulcerative colitis) not treated with a biologic agent within the past 6 months; patients were given their first infusion of infliximab at a hospital or clinic in Berlin, Germany. We collected data on clinical scores, levels of C-reactive protein, and ultrasound results (Limberg scores) at baseline (before the first infusion) and after 6 weeks (3rd infliximab infusion). PMBCs were obtained from patients at baseline and 10 healthy individuals (controls) and incubated with lipopolysaccharide. We measured production of cytokines (TNF, interleukin 1 [IL1], IL6, IL8, IL10, IL12p70, and IL22) by ELISA and performed cytometric bead array and flow cytometry analyses. The primary endpoint was clinical response (decrease in Harvey Bradshaw Index scores of 2 or more or decrease in partial Mayo scores of 3 or more at week 6) in patients with PBMCs that produced high vs low levels of TNF. RESULTS: Responders had a shorter median disease duration (P = .018) and higher median Limberg score (P = .021), than nonresponders. Baseline PBMCs from responders produced significantly more TNF (P = .049) and IL6 (P = .028) than from nonresponders; a level of 500 pg/ml TNF identified responders with 82% sensitivity and 78% specificity. In patients with Crohn's disease, this cutoff value (500 pg/ml TNF) identified responders with 100% sensitivity and 82% specificity; TNF levels above this level were independently associated with response to infliximab in multivariate analysis (odds ratio, 16.2; 95% CI, 1.8-148.7; P = .014). The percentage of TNF-positive cells was higher among CD14+ monocytes than lymphocytes after stimulation. CONCLUSIONS: Production of a high level of TNF by PBMCs (specifically CD14+ cells) from patients with IBD can identify those most likely to have a clinical response to infliximab therapy. In patients with Crohn's disease, a cutoff value of 500 pg/ml TNF identified responders with 100% sensitivity and 82% specificity.

Combined Endothelialization Promoting and Surface Binding Chimeric Conjugate with Low Thrombogenicity.

Endothelialization of blood contacting implants, e.g., vascular stents, is regarded as a prerequisite for an improved performance in terms of minimizing thrombogenicity and the inhibition of restenosis. Commonly used materials, such as Ti-based alloys, can be surface-modified in order to improve endothelial cell (EC) colonization as well as to reduce platelet adhesion. Standard modification techniques involve silanization and are laborious and time-consuming. We propose a novel single-step procedure based on a surface-recognizing peptide generated by phage display methodology. Combining this with a polyethylene glycol (PEG) spacer and an EC-specific sequence yielded a conjugate applicable for the modification of Ti surfaces.

Unintended conceptions leading to wanted pregnancies - an integral perspective on pregnancy acceptance from a mixed-methods study in Germany.

OBJECTIVE: The study examines the differences within unintended first pregnancies in the life course of 20-44 year old women. Special attention is paid to response and pregnancy acceptance. Exploring determinants and dynamics, this study will contribute to a better understanding of 'happiness with an unintended pregnancy', as this is assumed to be indicative of fewer social problems and health risks. METHODS: Retrospective survey data on first unintended pregnancies carried to term (n = 2,306) were analysed using bivariate analysis. Qualitative analysis of the narrations of such pregnancies (n = 59) used the technique of comparing cases. Standardised and qualitative data are available for first intended or aborted pregnancies as comparison groups. All data were collected from the cross-sectional mixed-methods study of 'Women's Lives: Family Planning in the Life Course' (2012-2018, Federal Centre of Health Education, Germany). RESULTS: Two-fifth of the unintended pregnancies carried to term were '(very) welcome'. Pregnancy intention, contraceptive use, living conditions, and attitudes had a significant impact. Five pathways of acceptance - sooner or later, more easy or hard to achieve - were identified in the qualitative data. CONCLUSION: Unintended pregnancies form a continuum ranging from readily accepted 'happy' pregnancies to pregnancies hard to accept. A new measure should also include postconception acceptance, besides preconception desire.

["Risk it"-why women who do not intend to get pregnant do not use contraception : Results of the BZgA study "Women's lives 3. Family planning in women's lives"]. / "Risk it" ­ warum Frauen ohne Schwangerschaftsabsicht nicht verhüten : Sonderauswertung der BZgA-Studie "frauen leben 3. Familienplanung im Lebenslauf von Frauen".

BACKGROUND: Despite widespread access to contraception, it is observed that women without pregnancy intention do not use contraception and become pregnant. AIM OF THIS PAPER: The analyses conducted in this paper aim to assess the prevalence of the phenomenon of non-use of contraception for Germany and to gain a better understanding of the reasons why women risk unintended pregnancy. MATERIALS AND METHODS: Using quantitative survey data on 17,400 pregnancies and 116 open qualitative interviews from the study "Women's lives 3: Family planning in women's lives" conducted on behalf of the Federal Centre for Health Education (BZgA), statements can be made on the prevalence of non-use of contraceptive methods despite a lack of pregnancy intention and on the underlying reasons. RESULTS: The reasons given for not using contraception can be assigned to three very different motives: a) playing with a desire to have children, which is mentioned by just under one third; b) individual and structural barriers, such as health reservations or too high costs; and c) not using contraception because of the erroneous assumption of not being able to get pregnant. It can be seen that these motives vary in prevalence depending on the biographical situation. DISCUSSION: The results point to the need for a more differentiated understanding of unintended pregnancies in both research and prevention. A limitation and thus a need for future research is that the influence of the (sexual) partner on the contraceptive behaviour of women and on the intentionality of the pregnancy cannot be examined within the framework of the study.

Endovascular simulation training: a tool to increase enthusiasm for interventional radiology among medical students.

OBJECTIVES: Interventional radiology (IR) is a growing field but is underrepresented in most medical school curricula. We tested whether endovascular simulator training improves medical students' attitudes towards IR. MATERIALS AND METHODS: We conducted this prospective study at two university medical centers; overall, 305 fourth-year medical students completed a 90-min IR course. The class consisted of theoretical and practical parts involving endovascular simulators. Students completed questionnaires before the course, after the theoretical and after the practical part. On a 7-point Likert scale, they rated their interest in IR, knowledge of IR, attractiveness of IR, and the likelihood to choose IR as subspecialty. We used a crossover design to prevent position-effect bias. RESULTS: The seminar/simulator parts led to the improvement for all items compared with baseline: interest in IR (pre-course 5.2 vs. post-seminar/post-simulator 5.5/5.7), knowledge of IR (pre-course 2.7 vs. post-seminar/post-simulator 5.1/5.4), attractiveness of IR (pre-course 4.6 vs. post-seminar/post-simulator 4.8/5.0), and the likelihood of choosing IR as a subspecialty (pre-course 3.3 vs. post-seminar/post-simulator 3.8/4.1). Effect was significantly stronger for simulator training compared with that for seminar for all items (p < 0.05). For simulator training, subgroup analysis of students with pre-existing positive attitude showed considerable improvement regarding "interest in IR" (× 1.4), "knowledge of IR" (× 23), "attractiveness of IR" (× 2), and "likelihood to choose IR" (× 3.2) compared with pretest. CONCLUSION: Endovascular simulator training significantly improves students' attitude towards IR regarding all items. Implementing such courses at a very early stage in the curriculum should be the first step to expose medical students to IR and push for IR. KEY POINTS: • Dedicated IR-courses have a significant positive effect on students' attitudes towards IR. • Simulator training is superior to a theoretical seminar in positively influencing students' attitudes towards IR. • Implementing dedicated IR courses in medical school might ease recruitment problems in the field.

Proteomics of Aspergillus fumigatus Conidia-containing Phagolysosomes Identifies Processes Governing Immune Evasion.

Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing. To get insight in the underlying molecular mechanisms, we comparatively analyzed proteins of mouse macrophage phagolysosomes containing melanized wild-type (wt) or nonmelanized pksP mutant conidia. For this purpose, a protocol to isolate conidia-containing phagolysosomes was established and a reference protein map of phagolysosomes was generated. We identified 637 host and 22 A. fumigatus proteins that were differentially abundant in the phagolysosome. 472 of the host proteins were overrepresented in the pksP mutant and 165 in the wt conidia-containing phagolysosome. Eight of the fungal proteins were produced only in pksP mutant and 14 proteins in wt conidia-containing phagolysosomes. Bioinformatical analysis compiled a regulatory module, which indicates host processes affected by the fungus. These processes include vATPase-driven phagolysosomal acidification, Rab5 and Vamp8-dependent endocytic trafficking, signaling pathways, as well as recruitment of the Lamp1 phagolysosomal maturation marker and the lysosomal cysteine protease cathepsin Z. Western blotting and immunofluorescence analyses confirmed the proteome data and moreover showed differential abundance of the major metabolic regulator mTOR. Taken together, with the help of a protocol optimized to isolate A. fumigatus conidia-containing phagolysosomes and a potent bioinformatics algorithm, we were able to confirm A. fumigatus conidia-dependent modification of phagolysosomal processes that have been described before and beyond that, identify pathways that have not been implicated in A. fumigatus evasion strategy, yet.Mass spectrometry proteomics data are available via ProteomeXchange with identifiers PXD005724 and PXD006134.

Low incidence of true Sternberg's canal defects among lateral sphenoid sinus encephaloceles.

BACKGROUND: Spontaneous sphenoid sinus cerebrospinal fluid (CSF) encephaloceles have been postulated to arise from a persistent Sternberg's canal. However, recent evidence has questioned this embryological etiology. We examined the anatomic location of a series of lateral sphenoid sinus encephaloceles to determine if they corresponded with the location of Sternberg's canal. METHODS: We queried a prospectively acquired database of surgically treated spontaneous CSF leaks and identified those arising from the sphenoidal sinus. Images were reviewed to characterize the leaks with respect to the foramen rotundum (FR) and the vidian canal (VC). Four leak types were classified of which Type I (medial to FR and VC entering nasopharynx) was theoretically located in the precise location of Sternberg's canal. Type II was medial to FR; Type III was lateral to FR; Type IV passed through an enlarged FR into sphenoid sinus. Demographic data were analyzed. RESULTS: Of 103 repaired CSF leaks, 17 arose from the lateral sphenoid sinus. There were no true Type I leaks, 3 Type II leaks, 12 Type III leaks, and 2 Type IV leaks. No differences were found with respect to sphenoid pneumatization, BMI, age, sex, arachnoid pits, or postoperative leak between different types. CONCLUSIONS: No evidence was found to support the existence of a classic Sternberg canal CSF leak, supporting the hypothesis that most sphenoid spontaneous leaks likely occur secondary to chronically elevated ICP. Rare cases may be related to a weakness in the sphenoid wall in the region of Sternberg's canal.

Distributed Optical Fiber-Based Approach for Soil-Structure Interaction.

Scour is a hydraulic risk threatening the stability of bridges in fluvial and coastal areas. Therefore, developing permanent and real-time monitoring techniques is crucial. Recent advances in strain measurements using fiber optic sensors allow new opportunities for scour monitoring. In this study, the innovative optical frequency domain reflectometry (OFDR) was used to evaluate the effect of scour by performing distributed strain measurements along a rod under static lateral loads. An analytical analysis based on the Winkler model of the soil was carefully established and used to evaluate the accuracy of the fiber optic sensors and helped interpret the measurements results. Dynamic tests were also performed and results from static and dynamic tests were compared using an equivalent cantilever model.

In Situ Monitoring of Groundwater Contamination Using the Kalman Filter.

This study presents a Kalman filter-based framework to establish a real-time in situ monitoring system for groundwater contamination based on in situ measurable water quality variables, such as specific conductance (SC) and pH. First, this framework uses principal component analysis (PCA) to identify correlations between the contaminant concentrations of interest and in situ measurable variables. It then applies the Kalman filter to estimate contaminant concentrations continuously and in real-time by coupling data-driven concentration-decay models with the previously identified data correlations. We demonstrate our approach with historical groundwater data from the Savannah River Site F-Area: We use SC and pH data to estimate tritium and uranium concentrations over time. Results show that the developed method can estimate these contaminant concentrations based on in situ measurable variables. The estimates remain reliable with less frequent or no direct measurements of the contaminant concentrations, while capturing the dynamics of short- and long-term contaminant concentration changes. In addition, we show that data mining, such as PCA, is useful to understand correlations in groundwater data and to design long-term monitoring systems. The developed in situ monitoring methodology is expected to improve long-term groundwater monitoring by continuously confirming the contaminant plume's stability and by providing an early warning system for unexpected changes in the plume's migration.

Secreted Frizzled-Related Protein 2 and Inflammation-Induced Skeletal Muscle Atrophy.

OBJECTIVE: In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-ß1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-ß1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled-related protein 2 reduction enhances transforming growth factor-ß1-mediated effects and investigated the interrelationship between transforming growth factor-ß1 and secreted frizzled-related protein 2 in inflammation-induced atrophy. DESIGN: Observational study and prospective animal trial. SETTING: Two ICUs and research laboratory. PATIENTS/SUBJECTS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores greater than or equal to 8 underwent a skeletal muscle biopsy from the vastus lateralis at median day 5 in ICU. Four patients undergoing elective orthopedic surgery served as controls. To search for signaling pathways enriched in muscle of ICU-acquired weakness patients, a gene set enrichment analysis of our recently published gene expression profiles was performed. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to analyze secreted frizzled-related protein 2 expression and protein content. A mouse model of inflammation-induced skeletal muscle atrophy due to polymicrobial sepsis and cultured myocytes were used for mechanistic analyses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gene set enrichment analysis uncovered transforming growth factor-ß1 signaling activation in vastus lateralis from ICU-acquired weakness patients. Muscular secreted frizzled-related protein 2 expression was reduced after 5 days in ICU. Likewise, muscular secreted frizzled-related protein 2 expression was decreased early and continuously in mice with inflammation-induced atrophy. In muscle, secreted frizzled-related protein 2 was predominantly contained in fast twitch/type II myofibers. Secreted frizzled-related protein 2 physically interacted and colocalized with transforming growth factor-ß1 through its cysteine-rich domain. Finally, secreted frizzled-related protein 2 prevented transforming growth factor-ß1-induced atrophy in C2C12 myotubes. CONCLUSIONS: Muscular secreted frizzled-related protein 2 is down-regulated in ICU-acquired weakness patients and mice with inflammation-induced muscle atrophy. Decreased secreted frizzled-related protein 2 possibly establishes a positive feedback loop enhancing transforming growth factor-ß1-mediated atrophic effects in inflammation-induced atrophy.