New Speakers and Language Revitalisation: Arpitan and Community (Re)formation

Today, it is uncontroversial to claim that France’s regional (minority) languages (RLs) are in decline. However, revitalisation movements have nonetheless continued to surface, and this chapter considers one by-product of such efforts: the emergence of new speakers in RL contexts. The term ‘new speaker’ refers to individuals who acquire the target language not through traditional transmission contexts (e.g. home, family), but instead as adults through language revitalisation initiatives. The chapter focuses on revitalisation efforts in the context of Francoprovençal, a severely endangered and understudied RL spoken transnationally across French, Italian and Swiss borders. A critical examination of current studies supplemented with recently collected empirical data shows new speakers to be central agents in a movement championing proto-nation-statehood across national borders, reorienting the region’s traditional sociolinguistic field

A method to evaluate equitable accessibility: combining ethical theories and accessibility-based approaches

In this paper, we present the case that traditional transport appraisal methods do not sufficiently capture the social dimensions of mobility and accessibility. However, understanding this is highly relevant for policymakers to understand the impacts of their transport decisions. These dimensions include the distribution of mobility and accessibility levels over particular areas or for specific population groups, as well as how this may affect various social outcomes, including their levels of participation, social inclusion and community cohesion. In response, we propose a method to assess the socially relevant accessibility impacts (SRAIs) of policies in some of these key dimensions. The method combines the use of underlying ethics principles, more specifically the theories of egalitarianism and sufficientarianism, in combination with accessibility-based analysis and the Lorenz curve and Gini index. We then demonstrate the method in a case study example. Our suggestion is that policymakers can use these ethical perspectives to determine the equity of their policies decisions and to set minimum standards for local transport delivery. This will help them to become more confident in the development and adoption of new decision frameworks that promote accessibility over mobility and which also disaggregate the costs and benefits of transport policies over particular areas or for specific under-served population groups

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint

© The Author(s) 2020. Background: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. Purpose: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. Study Design: Consensus statement. Methods: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. Results: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. Conclusion: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors

Physical Activity After Surgery for Severe Obesity: The Role of Exercise Cognitions

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Physical activity after bariatric surgery is associated with sustained weight loss and improved quality of life. Some bariatric patients engage insufficiently in physical activity. This may be due to exercise cognitions, i.e., specific beliefs about benefits of and barriers to physical exercise. The aim of this study was to examine whether and to what extent both physical activity and exercise cognitions changed at 1 and 2 years post-surgery and whether exercise cognitions predict physical activity. Methods Forty-two bariatric patients (38 women, 4 men; mean age 38±8 years, mean body mass index prior to surgery 47±6 kg/m 2) filled out self-report instruments to examine physical activity and exercise cognitions pre- and post-surgery

Increased Asymmetric Dimethylarginine in Severe Falciparum Malaria: Association with Impaired Nitric Oxide Bioavailability and Fatal Outcome

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is a predictor of mortality in critical illness. Severe malaria (SM) is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1) increased in proportion to disease severity, 2) associated with impaired vascular and pulmonary NO bioavailability and 3) independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM) and 19 healthy controls (HC). Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 µM; 95% CI 0.74–0.96) compared to those with MSM (0.54 µM; 95%CI 0.5–0.56) and HCs (0.64 µM; 95%CI 0.58–0.70; p<0.001). ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0–181; p = 0.01). ADMA was independently associated with decreased exhaled NO (rs = −0.31) and endothelial function (rs = −0.32) in all malaria patients, and with reduced exhaled NO (rs = −0.72) in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria

The Free Energy Landscape of Small Molecule Unbinding

The spontaneous dissociation of six small ligands from the active site of FKBP (the FK506 binding protein) is investigated by explicit water molecular dynamics simulations and network analysis. The ligands have between four (dimethylsulphoxide) and eleven (5-diethylamino-2-pentanone) non-hydrogen atoms, and an affinity for FKBP ranging from 20 to 0.2 mM. The conformations of the FKBP/ligand complex saved along multiple trajectories (50 runs at 310 K for each ligand) are grouped according to a set of intermolecular distances into nodes of a network, and the direct transitions between them are the links. The network analysis reveals that the bound state consists of several subbasins, i.e., binding modes characterized by distinct intermolecular hydrogen bonds and hydrophobic contacts. The dissociation kinetics show a simple (i.e., single-exponential) time dependence because the unbinding barrier is much higher than the barriers between subbasins in the bound state. The unbinding transition state is made up of heterogeneous positions and orientations of the ligand in the FKBP active site, which correspond to multiple pathways of dissociation. For the six small ligands of FKBP, the weaker the binding affinity the closer to the bound state (along the intermolecular distance) are the transition state structures, which is a new manifestation of Hammond behavior. Experimental approaches to the study of fragment binding to proteins have limitations in temporal and spatial resolution. Our network analysis of the unbinding simulations of small inhibitors from an enzyme paints a clear picture of the free energy landscape (both thermodynamics and kinetics) of ligand unbinding

Sexually Dimorphic Serotonergic Dysfunction in a Mouse Model of Huntington's Disease and Depression

Depression is the most common psychiatric disorder in Huntington's disease (HD) patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT) and the forced-swimming test (FST). The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT1A receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT2A receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2) mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice

Pseudomonas aeruginosa Population Structure Revisited

At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. However, some important issues, such as the worldwide emergence of highly transmissible P. aeruginosa clones among cystic fibrosis (CF) patients and the spread and persistence of multidrug resistant (MDR) strains in hospital wards with high antibiotic pressure, remain contentious. To further investigate the population structure of P. aeruginosa, eight parameters were analyzed and combined for 328 unrelated isolates, collected over the last 125 years from 69 localities in 30 countries on five continents, from diverse clinical (human and animal) and environmental habitats. The analysed parameters were: i) O serotype, ii) Fluorescent Amplified-Fragment Length Polymorphism (FALFP) pattern, nucleotide sequences of outer membrane protein genes, iii) oprI, iv) oprL, v) oprD, vi) pyoverdine receptor gene profile (fpvA type and fpvB prevalence), and prevalence of vii) exoenzyme genes exoS and exoU and viii) group I pilin glycosyltransferase gene tfpO. These traits were combined and analysed using biological data analysis software and visualized in the form of a minimum spanning tree (MST). We revealed a network of relationships between all analyzed parameters and non-congruence between experiments. At the same time we observed several conserved clones, characterized by an almost identical data set. These observations confirm the nonclonal epidemic population structure of P. aeruginosa, a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. One of these clones is the renown and widespread MDR serotype O12 clone. On the other hand, we found no evidence for a widespread CF transmissible clone. All but one of the 43 analysed CF strains belonged to a ubiquitous P. aeruginosa “core lineage” and typically exhibited the exoS+/exoU− genotype and group B oprL and oprD alleles. This is to our knowledge the first report of an MST analysis conducted on a polyphasic data set