Search

Global health (GH) and health-related quality of life are patient priorities in axial spondyloarthritis (axSpA). Our objective was to assess the relative importance of disease-related factors including disease activity, and patient-related factors including comorbidities, to explain GH in axSpA. Post hoc cross-sectional analyses of 4 sets (COMOSPA, PERSPA, COMEDSPA, and DESIR) of patients fulfilling ASAS criteria for axSpA. GH was assessed through the ASAS Health Index (ASAS-HI) or the EuroQoL-5D-3L (EQ-5D). Disease-related factors included disease activity (ASDAS, psoriasis, arthritis, enthesitis, and CRP), disease duration, diagnostic delay, bamboo spine, and treatment. Non-disease-related factors included sociodemographic characteristics, comorbidities and chronic widespread pain. Multivariable logistic and linear regressions and partial variances (R2) were applied to identify independent determinants of GH. In 6064 patients (range 284–2756 across datasets), mean age ranged 38.9–45.8 years, 51–68% were male. GH was generally moderate: median ASAS-HI ranged 5.0–7.0. GH was explained by ASDAS (range of odds ratios, OR, 2.60–4.48) and chronic widespread pain (range of OR 2.19–8.39); other determinants included comorbidities and sociodemographic characteristics. Only 47–57% of the total variance in GH could be explained by the models; disease activity (partial variance, 16–26%) and chronic widespread pain (partial variance 12–15%) were the key contributing variables. A wide range of disease and non-disease-related variables usually collected in studies could only explain 47–57% of the variability in GH. Among these, disease activity and chronic widespread pain were most relevant and of similar magnitude of importance. These findings will be helpful for shared decision-making. [ABSTRACT FROM AUTHOR]

Background: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. Methods: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. Results: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57–1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03–1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99–1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11–18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). Conclusion: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. Trial registration: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149. [ABSTRACT FROM AUTHOR]

Background and study aims: Esophageal mucosal bridge (EMB) may be diagnosed at the anastomotic site in children operated on for esophageal atresia (EA) but so far only a few cases (n = 4) have been reported. This study aimed to characterize EMB in children with EA, risk factors, and treatment. Patients and methods: This retrospective multicenter study recorded patient's characteristics, EMB diagnosis circumstances, endoscopic management, follow-up, and EMB recurrence in children with EA aged less than 18 years, compared with paired EA patients without EMB. Results: Thirty patients were included (60% male, 90% EA/tracheoesophageal fistula, 43% associated malformations). Compared to 44 paired controls, EMB was associated with a history of nasogastric tube feeding (31% vs. 9.1%, p = 0.02) and severe gastroesophageal reflux disease (history of fundoplication: 41.4% vs. 13.6%, p < 0.01). 77% had symptoms (food impaction and/or dysphagia). Endoscopic management was performed in 53% of patients (83% electrocoagulation) with no technical difficulties or complications. 80% of the symptomatic patients with EMB improved after endoscopic treatment, independently of anastomotic stricture dilatation or not. Conclusion: EMB endoscopic management by electrocoagulation is safe and often leads to symptom improvement. [ABSTRACT FROM AUTHOR]

This paper focuses on the concept of subjective age, which has mainly been studied in the fields of gerontology, psychology and marketing. This paper explores the potential effect of the rejuvenating trend on entrepreneurial intention (EI) among seniors based on a sample of 224 seniors aged 45 years old and more. A two-step procedure was performed to test our hypotheses: a hierarchical regression analysis and a bootstrapping procedure. The results reveal a direct effect of the rejuvenating trend on EI among seniors. Also it reveals that social norms mediate this effect. Future studies should integrate other ageing-related individual variables such as generativity, death anxiety and perceived health. As our findings reveal the entrepreneurial potential of seniors, it is necessary to create accompanying structures dedicated to this specific population. This is the first paper to explore the link between subjective age and EI, as prior research has mainly investigated the effect of chronological age. [ABSTRACT FROM AUTHOR]

Background: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. Objectives: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. Participants: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). Design: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. Main Measures: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. Key Results: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04–4.41), smell/taste disorder (26.5, 3.46–202), dyspnea (2.81, 1.10–7.16), and memory impairment (5.71, 1.53–21.3). Among COVID-positive, female gender (1.67, 1.09–2.56) and overweight/obesity (1.67, 1.10–2.56) were predictors of persistent symptoms. Conclusions: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society. [ABSTRACT FROM AUTHOR]

Essential fatty acids (EFA) and conjugated linoleic acids (CLA) are unsaturated fatty acids with immune-modulatory effects, yet their synergistic effect is poorly understood in dairy cows. This study aimed at identifying differentially abundant proteins (DAP) and their associated pathways in dairy cows supplied with a combination of EFA and CLA during the transition from antepartum (AP) to early postpartum (PP). Sixteen Holstein cows were abomasally infused with coconut oil as a control (CTRL) or a mixture of EFA (linseed + safflower oil) and CLA (Lutalin, BASF) (EFA + CLA) from − 63 to + 63 days relative to parturition. Label-free quantitative proteomics was performed on plasma samples collected at days − 21, + 1, + 28, and + 63. During the transition time, DAP, consisting of a cluster of apolipoproteins (APO), including APOE, APOH, and APOB, along with a cluster of immune-related proteins, were related to complement and coagulation cascades, inflammatory response, and cholesterol metabolism. In response to EFA + CLA, specific APO comprising APOC3, APOA1, APOA4, and APOC4 were increased in a time-dependent manner; they were linked to triglyceride-enriched lipoprotein metabolisms and immune function. Altogether, these results provide new insights into metabolic and immune adaptation and crosstalk between them in transition dairy cows divergent in EFA + CLA status. [ABSTRACT FROM AUTHOR]

Introduction: Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.Methods: Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1).Results: Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24-14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14-3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008).Discussion: We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access. [ABSTRACT FROM AUTHOR]

Diffusion couples of Ti and biphasic alloy Al-7wt%Si were produced and heat-treated at 535 °C for between 1 and 200 hours. The nature and thickness of the phases present in the reaction layer sequence were characterized using conventional techniques such as microprobe analysis and transmission electron microscopy. For short interaction times the interfacial reaction layer consists mainly of silicides, whereas aluminides are formed after times longer than 40h. This variation in the spatial reaction layer sequence over time is explained by the biphasic nature of one of the diffusion couple end-members, with high activity for both elements, and by the huge difference between the composition of the first phase formed at the initial interface and the average composition of the biphasic end-member. This situation, which can be observed in other systems, illustrates the difficulty of confirming that a true diffusion path has been attained in a diffusion couple. Most of the criteria that were first proposed by Kirkaldy and Brown, can apparently be fulfilled, but the system could continue shifting over time towards a more stable configuration. In some systems, as in the case of Al-Si-Ti, the slow kinetics can be problematic, making it impossible to predict a radical change in material properties. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT.Methods: A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005-2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann-Whitney tests, when appropriate. An exploratory analysis by Kaplan-Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT.Results: Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8-41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified.Conclusions: Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF. [ABSTRACT FROM AUTHOR]

Summary: In oncology clinical research, the analysis and reporting of adverse events is of major interest. A consistent depiction of the safety profile of a new treatment is as crucial in establishing how to use it as its antitumor activity. The advent of new therapeutics has led to major changes in the management of patients and targeted therapies or immune checkpoint inhibitors are administered continuously for months or even years. However, the classical methods of adverse events analysis are no longer adequate to properly assess their safety profile. Indeed, the worst grade method and time-to-event analysis cannot capture the duration or the evolution of adverse events induced by extended treatment durations. Many authors have highlighted this issue and argue that the analysis of safety data from clinical trials should be modernized by considering the dimension of time and the recurrent nature of adverse events. This paper aims to illustrate the limitations of current methods and discusses the value of alternative approaches such as the prevalence function, Q-TWiST, the ToxT and the recurrent event approaches. The rationale and design of the MOTIVATE trial, which aims to model the evolution of toxicities over time using the prevalence function in patients treated by immunotherapy, is also presented (ClinicalTrials.gov Identifier: NCT03447483; Date of registration: 27 February 2018). [ABSTRACT FROM AUTHOR]

Deficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-Invasive Escherichia coli (AIEC) are frequently observed in Crohn's disease (CD) patients. AIEC bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. Transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn's disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are associated with a decreased bone mineral density, but the impact on fractures is unknown. In our study, global risk of fracture is increased for patients with IBDs versus controls. This result will help to determine the appropriate assessment with early screening and management of osteoporosis. Inflammatory bowel diseases (IBDs), such as Crohn’s disease (CD) and ulcerative colitis (UC), are associated with a decreased bone mineral density (BMD). However, the impact on fracture risk is unknown and data are contradictory across studies. In this systematic review and meta-analysis, we aimed to assess the risk of fracture and presence of low BMD in patients with IBDs compared to healthy controls. A systematic search of literature was conducted of MEDLINE, EMBASE, the Cochrane library and abstracts from appropriate scientific congresses. Studies were selected if they compared the incidence of fractures and/or BMD measurement by dual-energy X-ray absorptiometry in patients with IBDs and healthy sex- and age-matched controls. Data were extracted by two independent investigators. Meta-analysis was performed with the inverse variance approach to estimate pooled odds ratios (ORs) and risk ratios (RRs) with their 95% confidence intervals (CIs). Twenty-four studies met the inclusion criteria. On the basis of nine studies, global risk of fracture was increased for patients with IBDs versus controls (RR = 1.38, 95% CI 1.11-1.73; p = 0.005). Fracture risk with IBDs was significantly increased for vertebral fractures (OR = 2.26, 95% CI 1.04-4.90; p < 0.001), but not for any other site. The analysis of 16 studies evaluating BMD showed a significant decrease in mean BMD and Z-scores for IBD patients versus controls at all sites. In our meta-analysis, patients with IBDs have an increased risk of fractures, especially in the spine, and significant decreased BMD at all sites, which suggests the need for identifying high-risk individuals among this population. [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant.Objective: To provide pragmatic guidelines on CR in each non-systemic JIA subtype.Methods: A multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee.Results: 74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA.Conclusion: These first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA.Key Points: • CR is a valuable imaging technique in selected indications. • CR is routinely recommended for peripheral joints, when damage risk is high. • CR is recommended according to the damage risk, depending on JIA subtype. • CR is not the first-line technique for imaging of the axial skeleton. [ABSTRACT FROM AUTHOR]

The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment. [ABSTRACT FROM AUTHOR]

Background: Our previous survey on first-in-human trials (FIHT) of monoclonal antibodies (mAbs) showed that, due to their limited toxicity, the recommended phase II dose (RP2D) was only tentatively defined.Methods: We identified, by MEDLINE search, articles on single-agent trials of mAbs with an FIHT included in our previous survey. For each mAb, we examined tested dose(s) and dose selection rationale in non-FIHTs (NFIHTs). We also assessed the correlation between doses tested in the registration trials (RTs) of all FDA-approved mAbs and the corresponding FIHT results.Results: In the 37 dose-escalation NFIHTs, the RP2D indication was still poorly defined. In phase II-III NFIHTs (n=103 on 37 mAbs), the FIHT RP2D was the only dose tested for five mAbs. For 16 mAbs, only doses different from the FIHT RP2D or the maximum administered dose (MAD) were tested and the dose selection rationale infrequently indicated. In the 60 RTs on 27 FDA-approved mAbs with available FIHT, the FIHT RP2D was tested only for two mAbs, and RT doses were much lower than the FIHT MAD.Conclusions: The rationale beyond dose selection in phase II and III trials of mAbs is often unclear in published articles and not based on FIHT data. [ABSTRACT FROM AUTHOR]

Purpose: Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision proves to be difficult. Clinical and pathological criteria are sometimes insufficient to determine the best therapeutic options, and validated biomarkers such as uPA/PAI-1, are needed to contribute to the decision-making. The objective of this study was to evaluate the clinical outcome of an unselected ER+/HER2− pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination. Method: This monocentric retrospective study included 520 patients who underwent curative surgery in our institute between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinical-pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels using fresh, extemporaneously sampled tissue. We evaluated the correlation between uPA/PAI-1 levels, clinical-pathological variables, and the patient's outcome (relapse-free survival, RFS, and overall survival, OS). Result: Median follow-up was 5.4 years. The 5- and 10-year RFS rates were ,respectively, 95 and 89%, and the five-year OS rate was 96.3%. Forty percent of tumors had low uPA/PAI-1 levels. Seventy-five percent of patients with low uPA/PAI-1 levels did not receive chemotherapy, when 25% did. Sixty percent of patients with high uPA and/or PAI-1 levels received chemotherapy, while 40% did not. No statistical significant correlation was found between the uPA/PAI-1 levels and RFS or OS. Conclusion: The personalization of the patients' treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice. [ABSTRACT FROM AUTHOR]

Regulatory limits on cadmium (Cd) content in food products are tending to become stricter, especially in cereals, which are a major contributor to dietary intake of Cd by humans. This is of particular importance for durum wheat, which accumulates more Cd than bread wheat. The contamination of durum wheat grain by Cd depends not only on the genotype but also to a large extent on soil Cd availability. Assessing the phytoavailability of Cd for durum wheat is thus crucial, and appropriate methods are required. For this purpose, we propose a statistical model to predict Cd accumulation in durum wheat grain based on soil geochemical properties related to Cd availability in French agricultural soils with low Cd contents and neutral to alkaline pH (soils commonly used to grow durum wheat). The best model is based on the concentration of total Cd in the soil solution, the pH of a soil CaCl extract, the cation exchange capacity (CEC), and the content of manganese oxides (Tamm's extraction) in the soil. The model variables suggest a major influence of cadmium buffering power of the soil and of Cd speciation in solution. The model successfully explains 88% of Cd variability in grains with, generally, below 0.02 mg Cd kg prediction error in wheat grain. Monte Carlo cross-validation indicated that model accuracy will suffice for the European Community project to reduce the regulatory limit from 0.2 to 0.15 mg Cd kg grain, but not for the intermediate step at 0.175 mg Cd kg. The model will help farmers assess the risk that the Cd content of their durum wheat grain will exceed regulatory limits, and help food safety authorities test different regulatory thresholds to find a trade-off between food safety and the negative impact a too strict regulation could have on farmers. [ABSTRACT FROM AUTHOR]

The evolution of TiC reinforcement during the high-temperature consolidation step of a particulate-reinforced Ti matrix composite has been studied. A four-step scenario has been highlighted starting with the dissolution of the smallest particles to reach C saturation of the Ti matrix, followed by a change in the TiC stoichiometry from the initial TiC composition to the equilibrium composition (TiC). This change in composition induces an increase in both the total mass fraction of reinforcement and the particle diameter. The diameter increase promotes contact between individual particles in the most reinforced domains and initiates an aggregation phenomenon that is responsible for the observed high growth rate of particles for heat treatment times shorter than 1 h. Finally Ostwald ripening is responsible for the growth of particles for longer heat treatment times. [ABSTRACT FROM AUTHOR]

Two fabrication schemes of magnetic metal-polymer nanocomposites films are described. The nanocomposites are made of graphene-coated cobalt nanoparticles embedded in a polystyrene matrix. Scheme 1 uses non-covalent chemistry while scheme 2 involves covalent bonding with radicals. Preservation of the net-moment of cobalt and electrical insulation are achieved by means of a core double-shell structure of cobalt-graphene-polystyrene. The graphene shell has two functions: it is a protective layer against metal core oxidation and it serves as the functionalization surface for polymer grafting as well. The polystyrene shell is used as an insulating layer between nanoparticles and improves nanoparticles dispersion inside the polystyrene matrix. The theoretical maximum volume filling ratio estimated at ~30 % is almost reached. The nanocomposites are shown to undergo percolation behavior but retain low conductivity (<1 S/m) at the highest filling ratio reached ~25 % leading to extremely low losses (10) at high frequency. Such low conductivity values are combined with large magnetization, as high as 0.9 T. Ability for radiofrequency applications is discussed in regards to the obtained magnetization. [ABSTRACT FROM AUTHOR]

In this study, we use NanoSIMS element and isotope ratio mapping and LA-ICP-MS trace element measurements to elucidate the origins of monazites from a restitic xenolith enclosed in a 13.5 ± 0.3 Ma andesitic lava (Slovakia). The xenolith/lava interaction is mainly characterized by the growth of a plagioclase-bearing corona around the xenolith and magmatic garnet overgrowths on primary metamorphic garnets within the xenolith. NanoSIMS images (Y, La, Pb, Th and U) and trace element analyses indicate that variations of HREE, Y and Eu contents in the monazite are correlated with the resorption and the following overgrowth of garnet and plagioclase in the xenolith. Three domains are distinguished in the monazite grains: the inherited Variscan core at ca. 310 Ma (M1 domain) characterized by low Y and HREE contents and a weak negative Eu anomaly; the inner rim (M2 domain) crystallized during the growth of the plagioclase magmatic corona (large negative Eu anomaly) and the resorption of metamorphic garnet (high HREE and Y contents); and the external rim (M3 domain) crystallized during the growth of the plagioclase corona (large negative Eu anomaly) and during the crystallization of magmatic garnet (low Y, HREE contents) at ~13 Ma, i.e. the age of the andesitic lava. The age and chemical zonation of the monazites attest to the preservation of primary monazite in the xenolith despite the interaction with the andesite lava. NanoSIMS imaging provides high-quality sub-µm scale images of the monazite that reveals chemical domains that were not distinguishable on WDS X-ray maps, especially for depleted elements such as U and Pb. Owing to its small size, the M2 domain could not be accurately dated by the LA-ICP-MS method. However, NanoSIMS isotopic maps reveal that the M2 domain has similar Pb/Th isotope ratios to the M3 domain and thus similar ages. These results support the hypothesis that melt-assisted partial dissolution-precipitation in monazite efficiently records chemical and mineralogical changes during xenolith/lava interaction. [ABSTRACT FROM AUTHOR]

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study ( n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event. [ABSTRACT FROM AUTHOR]

Purpose: Osteoid osteoma (OO) is a painful benign bone tumor of the young that is widely treated by percutaneous thermal ablation (PTA) with success rates close to 100 %. Nevertheless, some patients have recurrences. We reviewed the literature to understand whether these are true recurrences or incomplete treatments; to analyze safety and efficacy during long-term follow-up in a extremely large cohort of patients; to detail best-practice suggestions from the largest clinical trials as well as report their complications; and to recommend standards for future reporting. Materials and Methods: This study followed the Cochrane's guidelines for Systematic Reviews of Interventions. Inclusion criteria were as follows: (1) prospective or retrospective cohort study for PTA of OO under computed tomography (CT) guidance; (2) CT or magnetic resonance diagnosis; (3) radiofrequency ablation or interstitial laser ablation technique; (4) English language; (5) population <10 patients; (6) follow-up ≥12 months; and (7) original research. Risk of bias was assessed with a modified Newcastle-Ottawa Scale. Results: Two hundred fourteen articles were initially found. After applying the criteria mentioned previously, 27 PTA articles concerning 1,772 patients were chosen for inclusion. No exclusions were made due to risk of bias. Conclusion: The investigators proved the long-term efficacy and superiority of PTA for OO compared with other techniques. In 5 % of patients, however, the technique failed, and the researchers did not offer detailed exhaustive explanations. Future clinical trials for OO ablation should consider reporting essential procedure details and follow-up findings to allow for a meta-analysis. We provide both recommended standards for future reporting and suggestions for the prevention of recurrence. [ABSTRACT FROM AUTHOR]

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria on a French multicenter study. 210 patients with sensory neuropathies from 15 francophone reference centers for neuromuscular diseases were included in the study with an expert diagnosis of non-SNN, SNN or suspected SNN according to the investigations performed in these centers. Diagnosis was obtained independently from the set of criteria to be tested. The expert diagnosis was taken as the reference against which the proposed SNN criteria were tested. The set relied on clinical and electrophysiological data easily obtainable with routine investigations. 9/61 (16.4 %) of non-SNN patients, 23/36 (63.9 %) of suspected SNN, and 102/113 (90.3 %) of SNN patients according to the expert diagnosis were classified as SNN by the criteria. The SNN criteria tested against the expert diagnosis in the SNN and non-SNN groups had 90.3 % (102/113) sensitivity, 85.2 % (52/61) specificity, 91.9 % (102/111) positive predictive value, and 82.5 % (52/63) negative predictive value. Discordance between the expert diagnosis and the SNN criteria occurred in 20 cases. After analysis of these cases, 11 could be reallocated to a correct diagnosis in accordance with the SNN criteria. The proposed criteria may be useful for the diagnosis of probable SNN in patients with sensory neuropathy. They can be reached with simple clinical and paraclinical investigations. [ABSTRACT FROM AUTHOR]

In decorticate, unanaesthetized and curarized rabbit preparations displaying spontaneous fictive locomotor sequences, the firing pattern of neurones was recorded extracellularly in the L6-S1 spinal cord. These neurones, located in the intermediate part of the cord, were not invaded by antidromic stimulation of the hindlimb muscle nerves and thus were considered as interneurones (or propriospinal or tract cells ascending to the brain). When compared to the output from the ipsilateral muscle nerves, these neurones were classified as flexor (F INs) or extensor (E INs) according to the phase of the locomotor cycle when they displayed their maximal firing rate. Among 69 F INs, 33 maintained tonic firing during the periods between episodes of locomotor activity. Their maximal firing rate was in phase with the flexor efferent bursts of the locomotor sequence; during the extensor phase, they maintained an instantaneous frequency (i.f.) that was clearly above the resting i.f. Of these neurones, six became completely silent during the initial flexor-extensor coactivation that opened the sequence (F neurones) whereas the 27 others increased their firing rate at that time (F neurones). The other neurones (36 F) were silent between the locomotor episodes. Although most of them had a rhythmic activity limited to the flexor bursts, some fired throughout the locomotor sequence with a maximal rate during flexor bursts. All the 123 E neurones completely stopped firing during the flexor phase. As was the case for F- neurone firing, E neurone firing (34 neurones) occurred only during periods of locomotor activity. Among the neurones that displayed tonic activity between locomotor episodes, the E neurones (24 from 123) remained at this resting value during the extensor phase whereas the E neurones (65 neurones) showed an increased i.f. for all or part of this phase. These data, which suggest an asymmetrical genesis of the flexor and extensor activities in locomotion, need to be supported by further analysis. [ABSTRACT FROM AUTHOR]

The nature of liquid-solid phase equilibria in the Al-rich corner of the Al-Si-Ti system are determined by drawing three isothermal sections at 620, 680 and 727 °C. The solubility of Ti in Al-Si liquids is determined for four different compositions (0, 9, 13 and 18 at.%Si) at temperature below 800 °C. Combination of the two sets of experimental results leads to an attempt of liquidus projection. The primary crystallization surface of AlTi is found to extend up to 9.5 at.%Si in the liquid phase at 620 °C and 11 at.%Si at 727 °C. The solubility of Ti is found to be not significantly dependent on the Si content of the liquid. From DSC measurements and deduction on microstructure, the last invariant reaction of the solidification path is found to be quasi-peritectic: $${\text{L}} + \uptau_{1} - {\text{Ti}}_{7} {\text{Al}}_{5} {\text{Si}}_{12} \Leftrightarrow {\text{Al}} + {\text{Si}} .$$ [ABSTRACT FROM AUTHOR]

Objective: To assess sacroiliac joint (SIJ) modifications on MRI and their ability to predict axial spondyloarthritis (SpA) with the purpose of identifying parameters for future prospective studies. Methods: Retrospective study was carried out of 110 consecutive patients referred for SIJ MRI with coronal, axial short TI inversion recovery (STIR), and axial T1 sequences over 6 months. Factors associated with SpA, including MRI SIJ modifications (fat deposition, structural abnormalities on T1-weighted images, and bone marrow edema [BME] on STIR sequences) and age were explored using multivariate logistic regression. The reference diagnosis was made 1-1.5 years later based on clinical, radiological, and biological findings, according to Assessment of SpondyloArthritis International Society (ASAS) criteria. Results: Twenty-eight patients were diagnosed with SpA (female/male: 19/9, age 41 ± 13 years). Abnormal findings were found in up to 21 % of patients without SpA (including 11 % with BME), versus 64 % of SpA patients (50 % with BME). A threshold age of 42.6 years was found to discriminate SpA patients (ROC AUC: 0.71, 95 % CI: 0.59-0.81). BME location in the sacral (OR: 7.07 [1.05, 47.6], p = 0.044) and both sacral and iliac areas (OR: 36.0 [5.61, 231], p = 0.0002), as well as age (OR: 0.95 [0.92, 0.98], p = 0.0019) were found to be independent predictors of SpA. 83.6 % of patients were effectively diagnosed using BME location and patient age in a classification and regression tree (CART) algorithm (sensitivity: 61 %, specificity: 91 %, PPV: 71 %, NPV: 87 %). Conclusion: The BME location combined with the patient's age (threshold 42.6 years) could help predict SpA. Further studies are required before these features can be used by radiologists to boost their confidence in reporting SIJ MRI. [ABSTRACT FROM AUTHOR]

Purpose: Lower urinary tract dysfunction is common in multiple sclerosis (MS). The purpose of this study was to prospectively evaluate the impact of intermittent catheterization (IC) on the quality of life of patients affected by MS. Methods: Between 2007 and 2009, we admitted 23 patients to teach them the technique of IC. Their quality of life was evaluated before and more than 6 months after the beginning of learning the technique, when the urinary situation was stable. Two questionnaires were used: one specific for urinary disorders (QUALIVEEN ®) and one general (SF-36 ®). Results: Twenty-two patients followed this different way of bladder emptying. More than 6 months (9.3 ± 3 months on average) after first learning to use IC, the impact of urinary disorders explored by Qualiveen ® had significantly decreased (the overall quality of life; bother with limitation; fears; feelings; Wilcoxon’s test, respectively p = 0.004; 0.007; 0.02; 0.02) while the quality of life was not diminished. Conclusion: Intermittent catheterization (IC) in association with overall urinary management, among patients affected by MS, is well accepted and reduces the impact of urinary dysfunction on their quality of life. [ABSTRACT FROM AUTHOR]

The skeletal anatomy of the hip provides two main locations for impingement: abnormal contact between the acetabulum and femur (femoroacetabular impingement) or between the ischium and femur (ischiofemoral impingement). We report a case of bilateral ischiofemoral impingement in a patient with hereditary multiple exostoses. The association of exostoses and femoral metaphyseal widening resulted in the narrowing of the ischiofemoral spaces. Pain was improved on the left side by resection of the ischial exostosis. [ABSTRACT FROM AUTHOR]

Objectives: This report reviews the cost effectiveness of different therapeutic interventions used in the treatment of ankylosing spondylitis (AS). Methods: We performed a systematic search of the databases MEDLINE via PubMed, EMBASE and the Cochrane Library and used hand-searching to identify articles on cost effectiveness of therapies for adult patients with AS published up to November 2010. Results: Of 135 articles, 13 studies were analysed. Two articles were on physical therapies, one article was on NSAIDs and ten articles were on tumour necrosis factor (TNF) inhibitors (infliximab = 6, etanercept = 2, infliximab and etanercept = 1 and adalimumab = 1). Of the latter, no article directly compared TNF inhibitors. Articles showed substantial heterogeneity in methodological approaches and thus results, which prevented us from any extensive comparison, data pooling or meta-analysis. The incremental cost effectiveness ratio (ICER) for spa-exercise treatment was ϵ7465 (95% CI 3294, 14 686) per QALY. The ICERs for infliximab, etanercept and adalimumab were ϵ5307-237 010, h29 815-123 761 and ϵ7344-33 303 per QALY, respectively. Conclusions: Modelling treatment strategies in chronic relapsing diseases such as AS presents specific challenges, as reflected in the variation in the cost-effectiveness results reported. Although quite variable, the cost-effectiveness ratios for AS therapies remain within an acceptable range. [ABSTRACT FROM AUTHOR]

Machine material handling is complicated in micromanufacturing since standards are not applied and existing handling systems are not flexible. Usually, machine handling systems are highly dependent of microcomponent properties. If the microcomponent is changed, the handling system is also changed. The aim of this paper is to propose a packaging station based on a standard carrier to provide a product-independent inter-machine handling system. Microcomponents are arranged into standard carriers for unifying transport systems. This packaging station was designed to accomplish micro-bulk-forming requirements, but its modular design and its low microcomponent dependencies permit to easily adapt the station to new applications. [ABSTRACT FROM AUTHOR]

The aim of this work was to characterize the chemical changes during solid state solution heat treatment of a metallurgically bonded steel/Al-Si interface. For this purpose, low carbon steel plates covered with the A-S7G03 aluminium alloy (7 wt.% Si, 0.3 wt.% Mg analogous to A356) were prepared by dip coating, water-quenching to room temperature and reheating in the solid state at 480-560 °C for 3-160 h. Upon reheating at 535 °C, a reaction layer was observed to grow at the interface between steel and the iron-saturated Al-Si alloy. As long as an intimate contact could be maintained, the total thickness, x, of the reaction layer increased with time, t, according to a nearly parabolic growth law x = K· t − b. At 535 °C, the value of the growth constant was K = 4.045 × 10 m s. This constant was found to be thermally activated [ K = K exp(− Q/ RT)] with K = 4.37 × 10 m s and Q = 153 kJ mol. The whole chemical interaction process was controlled by solid state volume diffusion and the reaction layer sequence corresponded to a diffusion path in the Al-Fe-Si phase diagram. A striking feature of the reaction process is the unbalanced diffusion of aluminium atoms through the reaction zone which rapidly results in the formation of Kirkendall voids. As these voids coalesce, solid state diffusion becomes more and more difficult and the steel/alloy bond gets weakened. Oxidation appears to be an aggravating factor, where applicable. [ABSTRACT FROM AUTHOR]

To describe the characteristics of peripheral neuropathy related to acute parvovirus B19 (B19V) infection. We reviewed clinical, electrophysiological and histological data of three patients with peripheral neuropathy and positive B19V detection (IgG, IgM and PCR) compatible with acute infection. The neuropathy fulfilled criteria for mononeuropathy multiplex (MM). It could be preceded by or concurrent with a limited purpuric eruption, but systemic manifestations were absent. The first neurological symptoms were always sensory and localized in a hand. Neuropathy was initially limited to a restricted sensory part of a nerve trunk territory. The course was subacute with successive and asymmetric injury of the limb and cranial nerves. Electromyographic study confirmed the diagnosis of MM with multifocal asymmetric sensory and motor axonal loss in two patients, whereas the neuropathy was purely sensory and limited to two nerves in the other patient. Nerve biopsies showed no evidence of necrotizing vasculitis but, in one patient, revealed a lymphocytic perivascular infiltrate evocative of hypersensitivity vasculitis secondary to an infectious agent. Intravenous immunoglobulin (IVIg) was systematically administered. Long-term outcome was good but with incomplete sensory recovery and, for one patient, persistence of a functional disability. B19 V infection should be considered in the etiological assessment of MM, especially in the event of a progressive sensory disorder in the hands and a concomitant history of rash. IVIg may be an effective treatment for this inflammatory disorder. [ABSTRACT FROM AUTHOR]

In the present paper we study the effect of high-permeability self-polarized thin films on the characteristics of high-impedance surfaces. Analytical and numerical models are compared by using the anisotropic effective medium theory method and a full-wave simulation tool, respectively. Experimental measurements are shown and lead to a good agreement with both numerical and analytical calculations. The main objective of this paper is to predict the impact of the permeability and conductivity of the material on artificial magnetic conductor structures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire, a 47-item disease-specific instrument evaluating Health-Related Quality of Life (HRQL) in human immunodeficiency virus (HIV)-infected patients. Methods: Treatment-experienced HIV-infected patients from two clinical programmes ( N = 565; N = 1,096) completed the FAHI at Baseline and after 24 weeks of treatment. Psychometric properties of the FAHI were assessed in both trial populations, including minimal important differences (MIDs) calculations. Links between HRQL assessed by FAHI Total score, and biological endpoints were explored by regression analysis and mean score comparisons. Results: Cronbach's alphas ranged from 0.72 to 0.94. Most items met convergent and discriminant validity criteria. Better FAHI scores were seen for patients in earlier HIV stages. Responsiveness was demonstrated with changes in FAHI scores significantly linked to change in EQ-5D score. Depending on methods used, MIDs ranged from 3.2 to 14 for FAHI Total score. Small association was found between FAHI Total score and CD4 count and viral load ( r-square < 3%). Mean changes in FAHI scores were not statistically related to viral response. Conclusions: The FAHI demonstrated acceptable psychometric properties in two independent populations. HRQL assessment enabled detection of changes in patients' health status not revealed by traditional efficacy endpoints. [ABSTRACT FROM AUTHOR]

The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach’s alpha: 0.75–0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument. [ABSTRACT FROM AUTHOR]

Lack of standardization is often a key problem area limiting the applications of any new automated micro-handling technology, due to that equipment makers may have to spend an excessive amount of time and resources to customize automation solutions. Carrier-based material handling systems provide product-independent solutions. Product independency is an essential requirement for re-using material handling systems, because they allow product change without mechanical changes in the transport devices. This paper describes a new automated inter-machine material handling system for micro-manufacturing integration, based on the standard carrier DIN-32561. The main task of the system is to transport (full/empty) carriers between different stations/machines in a micro-manufacturing plant, to integrate assembly and manufacturing. The authors designed a conveyor belt and an automated guided vehicle system to fit into a linear pick-and-place micro-manufacturing plant. Prototypes of the different components were then developed and tested. [ABSTRACT FROM AUTHOR]

Recently, the ternary carbide Ti3SiC2 has gained much attention due to its unique characteristics combining the properties of metals and ceramics (i.e., a low density, decent thermal and electrical conductivities, an excellent thermal shock resistance, a good machinability, damage tolerance, low friction, and so on). This study describes an investigation of the wettability in high vacuum of bulk Ti3SiC2 by a classical braze alloy based on the Ag–Cu–Ti system. Two techniques, i.e., the sessile drop and dispensed drop methods, were utilized. The results indicated that spreading kinetics is controlled by deoxidation kinetics of Ti3SiC2 surface under vacuum. The final contact angle on clean Ti3SiC2 is very small (~10°), testifying the development of strong, metallic interactions across the liquid–solid interface. The reactivity between the ternary carbide and the liquid phase during isothermal heating at 800 °C was also considered. [ABSTRACT FROM AUTHOR]

Reaction zones formed at 790 °C between solid titanium and liquid Ag-Cu eutectic alloys (pure and Ti-saturated) have been characterized. When pure Ag-Cu eutectic alloy with 40 at.% Cu is used, the interface reaction layer sequence is: αTi/Ti2Cu/TiCu/Ti3Cu4/TiCu4/L. Because of the fast dissolution rate of Ti in the alloy, the reaction zone remains very thin (3-6 μm) whatever the reaction time. When the Ag-Cu eutectic alloy is saturated in titanium, dissolution no longer proceeds and a thicker reaction zone with a more complex layer sequence grows as the reaction time increases. Four elementary chemical interaction processes have been identified in addition to Ti dissolution in the liquid alloy. These are growth of reaction layers on Ti by solid state diffusion, nucleation and growth from the liquid of TiCu4, isothermal solidification of silver and, finally, chemical conversion of the Cu-Ti compounds by reaction-diffusion in the solid state. A mechanism combining these processes is proposed to account for the constitution of Ti/Ag-Cu/Ti joints brazed at 780-800 °C. [ABSTRACT FROM AUTHOR]