Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.

In Europe, organic food must comply with specific regulations which do not include nutritional criteria. The ability of organic food to meet the nutritional needs of children is not assessed. This narrative review discusses the nutritional composition (macronutrients, micronutrients) of organic food compared with conventional products and its clinical relevance with a paediatric focus, as well as the health impact of these differences and of contaminants which interfere with metabolism. Other potential differences, particularly regarding the direct/indirect exposure to other contaminants in conventional food, are not addressed in this review. The composition of some organic food may differ from conventional food. Protein content was lower in cereals and eggs. A lower n-6:n-3 polyunsaturated fat (PUFA) ratio was observed in milk, meat and eggs. Long-chain PUFA and vitamin E may be higher in milk, meat and fish, as well as some minerals and antioxidants (phenolic compounds, vitamin C) in fruits, vegetables and starchy food and carotenoids in fruits and vegetables. Epidemiological studies suggest an association between organic diets and lower prevalence of childhood obesity, type 2 diabetes and metabolic syndrome, whereas the protective effect on allergy and cancer is controversial. Some organic food may be of greater nutritional interest for children’s diet than conventional food. Standardised studies comparing food composition and diet in children are needed. Considering the lower toxicologic risk and the sustainability of organic food, the Committee on Nutrition encourages the use of organic food, provided that such food is affordable, alongside specific baby food which is subject to strict specific European Union regulations.

In this article, we argue that the low-tech narrative redefined by a French low-tech movement in recent years can be considered as a legitimate research object for design research. Based on the French low-tech movement's literature, we present the definitions of the low-tech concept as an approach driven by principles and highlight two theorical limitations of this type of definition. Based on a value-sensitive design approach, we present transdisciplinary research results through a value-driven low-tech model and discussed its limitations and possible use as a tool for engineers.

The aetiology of cyanosis could be unclear in children, even for specialised paediatricians. Two cases were reported: first, a 6-year-old child with features of left isomerism and Fallot was fortuitously diagnosed with anomalous hepatic venous drainage before complete repair. Second, a newborn with an antenatal diagnosis of ductus venosus agenesis had an isolated intermittent right-to-left atrial shunt when upright, with favourable outcome, in contrast to the association with significant heart malformations including inferior caval vein interruption. Multimodality imaging and 3D printing helped to rule out extracardiac causes of persistent cyanosis and plan surgical repair.

We explore the effects of online customer ratings on financial policy. Using a large sample of Parisian restaurants, we find a positive and economically significant relationship between customer ratings and restaurant debt. We use the locally exogenous variations in customer ratings resulting from the rounding of scores in regression discontinuity tests to establish causality. Favorable online ratings reduce cash flow risk and increase resilience to demand shocks. Consistent with the view that good online ratings increase the debt capacity of restaurants and their growth opportunities, restaurants with good ratings use their extra debt to invest in tangible assets.

Adult sex ratios (ASRs) have proved to correlate with population trends, which make them potential useful indicators of a species’ population trajectory and conservation status. We analysed ASRs and proportion of juveniles in flocks of an endangered steppe bird, the Little Bustard Tetrax tetrax, using surveys made during the non-breeding period in seven areas within its Western European range (one in Portugal, four in Spain, and two in France). We found overall male-biased ASRs, as all the seven surveyed areas showed a male-biased ASR mean value. Five areas were below the threshold median value (female sex ratio = 0.4) considered to be consistent with an increased probability of extinction, according to earlier population viability analyses for the species. We also found a significant positive correlation between female ratio and the proportion of young individuals in the non-breeding flocks surveyed. Our results (strongly male-biased ASRs) support the hypothesis that the viability of Little Bustard populations in Western Europe is threatened by an excess of female mortality, something that should be quantified in the future, and emphasise the value of monitoring sex ratio as a population viability indicator in species where monitoring survival is difficult to achieve.

Mail-delivered get-out-the-vote (GOTV) field experiments have been found to increase voter turnout in some but not all contexts. We hypothesize that mail-delivered GOTV interventions are more successful in low-salience elections and test this in a systematic way for the first time. Relying on a systematic literature review and a meta-regression framework, we find that primary elections have a strong and significant positive impact on the success of mail-delivered GOTV interventions, whereas other commonly used measures of election salience, such as voter turnout, margin of victory, and a dummy for local elections, do not. These results highlight the possibility of fostering voter turnout using GOTV mail messages, especially in primary elections.

The low value of the speed of sound in dilute granular media permits the study of the properties of supersonic flows for a wide range of Mach numbers. In this paper, we report the experimental observation of a subsonic–supersonic transition in a vibrated granular gas. The shock fronts studied are obtained by simply pushing a rectangular obstacle into the granular gas for different obstacle velocities. The supersonic regime is characterized by the formation of normal shock waves whose width increases when the Mach number decreases to values close to 1. The bimodal model proposed by Mott-Smith in the 1950s provides a good description for the velocity distributions as well as the macroscopic quantities for shock waves in molecular gases but remains inadequate for dissipative media like granular gases and plasmas. Here by examining the shock front structure for a wide range of Mach numbers, we adapt the Mott-Smith bimodal description to a dissipative medium. By using balance equations from granular kinetic theory and taking into account different dissipation sources, the proposed model allows us to understand how this dissipation modifies temperature, mean velocity and volume fraction profiles through the shock front.

Since September 2016, the first release (DR1) of the Gaia catalogue was appeared. The optical Gaia positions of sources will be linked to the ICRF (VLBI radio positions of mostly quasars, QSOs). For high accurate link we need to investigate variations of optical flux of QSOs via their magnitude variations using data of ground-based telescopes. To do that, from 2013 we observed 47 QSOs and other sources; nine optical telescopes were used for that monitoring. To increase the total number of objects for the link, after a first set of 70 objects (Bourda et al. 2008), Bourda et al. (2011) established a second set of 47 objects. It is necessary to investigate the photometry and morphology of these objects. We collected ground-based data of QSOs (B, V and R mag) and compared with G mag of Gaia DR1; some results are presented here.

The reliability of paleovegetation records inferred from soil phytolith assemblages and SOM (soil organic matter) carbon isotope analysis was examined in light of previous pollen and charcoal reconstructions. The sampled latosol is located in south-central Brazil (Salitre), at a boundary between forest and cerrado. The derived mean age of phytoliths and SOM at each level is the result of a balance between continuous translocation and selective dissolution. It increases with depth in a regular, quantifiable fashion that allows paleoenvironmental interpretation. Phytoliths and SOM tracers first record a savanna phase, associated with the last Holocene long dry period occurring between ca. 5500 and 4500 yr B.P. Two periods of tree community development followed, between ca. 4000 and 3000 and after ca. 970 yr. B.P., leading to the present cerrado/forest association. The dry spell interrupted this trend about 970 ± 60 yr B.P. The second development of woody elements was contemporaneous with an increase in anthropogenic fires. Therefore, climate was more important than fires and human activities in constraining the growth of vegetation during the last nine centuries at Salitre. More generally, despite pedogenic processes, soil phytoliths and δ13C values of the SOM may be accurate tracers of vegetation changes.

The reliability of phytolith assemblage analysis for characterizing Mediterranean vegetation is investigated in this study. Phytolith assemblages are extracted from modern and buried Holocene soils from the middle Rhône valley (France). The relation between modern phytolith assemblages and the surrounding vegetation, as well as between fossil assemblages and contemporaneous vegetation, already reconstructed through other proxies, is discussed. We demonstrate that the main northwestern Mediterranean biomes are well distinguished by soil phytolith assemblage analysis. In particular, the density of pine and nonconiferous trees (densities expressed relatively to the grass cover) and the overall degree of opening of the vegetation appear well recorded by three phytolith indexes. North Mediterranean vegetation changes during the Holocene period, mainly tree line shifts, pine wood development and deforestation are poorly documented, due to the scarcity of proxy-preserving sites. Phytolith assemblage analysis of soils, buried soils, and sediments appears to be a promising technique to fill this gap.

Whispering gallery modes (WGMs) have been widely studied over the past 20 years for various applications, including biological sensing. While the WGM-based sensing approaches reported in the literature have shown tremendous performance down to single molecule detection, at present such sensing technologies are not yet mature and still have significant practical constraints that limit their use in real-world applications. Our work has focused on developing a practical, yet effective, WGM-based sensing platform capable of being used as a dip sensor for in-vivo biosensing by combining WGM fluorescent microresonators with silica Microstructured Optical Fibers (MOFs).

We recently demonstrated that a suspended core MOF with a dye-doped polymer microresonator supporting WGMs positioned onto the tip of the fiber, can be used as a dip sensor. In this architecture the resonator is anchored to one of the MOF air holes, in contact with the fiber core, enabling a significant portion of the evanescent field from the fiber to overlap with the sphere and hence excite the fluorescent WGMs. This architecture allows for remote excitation and collection of the WGMs. The fiber also permits easy manipulation of the microresonator for dip sensing applications, and hence alleviates the need for a complex microfluidic interface. More importantly, it allows for an increase in both the excitation and collection efficiency compared to free space coupling, and also improves the Q factor.

In this paper we present our recent results on microstructured fiber tip WGM-based sensors and show that this sensing platform can be used in clinical diagnostics, for detecting various clinically relevant biomarkers in complex clinical samples.

This paper describes a concept of stepped impedance resonators (SIR) built from two coaxial structures fitted inside one another. The resonator is built out of a succession of two coaxial sections in cascade, where the ground conductor of the first one is the central core of the next, or vice-versa. An advantageous property of SIR is that they allow a substantial reduction in size, while keeping away the first harmonic and without strongly degrading the quality factor. After describing the theoretical behavior of the resonator, we will then present the specific properties of this approach in second order filter, conceived, and realized in the UHF band. With this example, we will also address flexibility and tunability aspects, which are the other potentially useful properties of the structure. Measurements and simulations are presented and discussed. The architecture resembles a set of two Russian dolls that fit inside one another.

Lactose malabsorption is associated with rapid production of high levels of osmotic compounds, such as organic acids and SCFA in the colon, suspected to contribute to the onset of lactose intolerance. Adult rats are lactase deficient and the present study was conducted to evaluate in vivo the metabolic consequences of acute lactose ingestion, including host–microbiota interactions. Rats received diets of 25 % sucrose (S25 control group) or 25 % lactose (L25 experimental group). SCFA and lactic acid were quantified in intestinal contents and portal blood. Expression of SCFA transporter genes was quantified in the colonic mucosa. Carbohydrate oxidation (Cox) and lipid oxidation (Lox) were computed by indirect calorimetry. Measurements were performed over a maximum of 13 h. Time, diet and time × diet variables had significant effects on SCFA concentration in the caecum (P< 0·001, P= 0·004 and P= 0·007, respectively) and the portal blood (P< 0·001, P= 0·04 and P< 0·001, respectively). Concomitantly, expression of sodium monocarboxylate significantly increased in the colonic mucosa of the L25 group (P= 0·003 at t= 6 h and P< 0·05 at t= 8 h). During 5 h after the meal, the L25 group's changes in metabolic parameters (Cox, Lox) were significantly lower than those of the S25 group (P= 0·02). However, after 5 h, L25 Cox became greater than S25 (P= 0·004). Thus, enhanced production and absorption of SCFA support the metabolic changes observed in calorimetry. These results underline the consequences of acute lactose malabsorption and measured compensations occurring in the host's metabolism, presumably through the microbiota fermentations and microbiota–host interactions.

Background: We currently use the depression subscale (HADD) of the Hospital Anxiety and Depression Scale (HADS) for depression screening in elderly inpatients. Given recent concerns about the performance of the HADD in this age group, we performed a quality-control study retrospectively comparing HADD with the diagnosis of depression by a psychiatrist. We also studied the effect of dementia on the scale's performance.

Methods: HADS produces two 7-item subscales assessing depression or anxiety. The HADD was administered by a neuropsychologist. As “gold standard” we considered the psychiatrist's diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Patients older than 65 years, assessed by both the HADD and the psychiatrist, with a clinical dementia rating (CDR) score lower than 3, were included. The effect of dementia was assessed by forming three groups according to the CDR score (CDR0–0.5, CDR1, and CDR2). Simple and multiple logistic regression models were applied to predict the psychiatrist's depression diagnosis from HADD scores. Areas under the receiver operating characteristics curve (AUC) were plotted and compared by χ2 tests.

Results: On both univariate and multiple analyses, HADD predicted depression diagnosis but performed poorly (univariate: p = 0.009, AUC = 0.60 (95% confidence interval (CI) = 0.53–0.66); multiple: p = 0.007, AUC = 0.65 (95% CI = 0.58–0.71)), regardless of cognitive status. Because mood could have changed between the two assessments (they occurred at different points of the hospital stay), the multiple analyses were repeated after limiting time interval at 28, 21, and 14 days. No major improvements were noted.

Conclusion: The HADD performed poorly in elderly inpatients regardless of cognitive status. It cannot be recommended in this population for depression screening without further study.

Complex segments consisting of two phases are potentially ambivalent as to which phase determines their phonemic status – e.g. whether // is a stop or a nasal. This theoretical problem is addressed here with respect to a typologically unusual phoneme in Hiw, an endangered Oceanic language of Vanuatu. This complex segment, //, combines a velar voiced stop and a velar lateral approximant. Similar phonemes, in the few languages which have them, have been variously described as (laterally released) stops, affricates or (prestopped) laterals. The nature of Hiw // can be established from its patterning in tautosyllabic consonant clusters. The licensing of word-initial CC clusters in Hiw complies with the Sonority Sequencing Principle, albeit with some adjustments. Consequently, the well-formedness of words like /mejiŋə/ ‘berserk’ relies on // being analysed as a prestopped velar lateral approximant – the only liquid in the system.

In space, photometric surveys are very efficient to detect small transiting planets or stars which are contaminated by blended eclipsing binaries. We present some simulations compared to radial velocity (RV) observations obtained with the SOPHIE spectrograph (OHP, France) in order to determine the true nature of a brown dwarf candidate revealed by CoRoT: a background eclipsing binary diluted by a foreground star.