Clitic pronouns are linguistic elements which stand at the crossroads between different areas of the language faculty. They have specific morphology, syntax, and discourse functions. Use of this element requires the management of several aspects that draw from these areas of language. Clitics have been shown to appear early in typical acquisition, but to require longer for all aspects to be correctly managed, and they proved effortful in other modes of acquisition and atypical language, where they are clinical markers of impairment. In this work, we implement a comprehensive assessment of clitics aiming to investigate in what way different occurrences of this structure highlight different patterns of linguistic performance. To do so, we focus both on accuracy across conditions and on answer strategies, with an experimental protocol testing the following: comprehension of reference in binding constructions, production of clitics in two argument positions (direct object and indirect object), production of clitics in two sentence positions (preverbal and postverbal), production of clitics with different person features (1st/2nd and 3rd), and pragmatic abilities in the alternation with the lexical noun phrase and in perspective shift contexts. The assessment was tested on the following groups of native speakers of Italian: a group of pre-school and primary school typically developing children (Study 1), a group of adult heritage speakers of Italian living in the UK (Study 2), and four (pre)adolescents with a diagnosis of ASD (Study 3). Results found in this work showed that a comprehensive assessment of clitics can highlight similarities as well as differences in linguistic profiles according to different groups. Specifically, comprehension was not a discriminating factor in the populations: all populations tested showed to have access to abstract representations of clitics in binding constructions, as comprehension of simple clitics was generally unproblematic. An exception was found in the pre-schoolers, but this may have been due to task-related factors. In line with previous results on typical, atypical, and bilingual populations, production of Italian 3rd person direct object clitics with finite verbs showed different patterns across populations: in our data, typical children of all ages and ASD pre-adolescents showed to correctly produce this instance of the clitic the majority of the time, while heritage speakers of Italian showed poor production rates on this instance of the clitic. Importantly, our data shows similar results for indirect objects, showing that if the cliticization process is accessible, it is accessible regardless of the argument position occupied by the cliticised object. Another crucial result is that our studies find different patterns to be highlighted by the production of clitics on non-finite verbs as opposed to those on finite verbs: accuracy is similarly high in one high-performing ASD pre-adolescent and in the group results of 8-year-old children, but 4-year-old and 6-year-old children, as well as some ASD participants show chance or below chance performance in enclisis. The same was true for production of clitic combinations, although it was the least accurate structure across all groups, particularly in non-finite constructions. Here, heritage speakers and a few ASD speakers produce little to no instances of this construction, while those who produce it the most are the highest performing ASD participant and the oldest group of children. It is plausible to assume that the derivation of both enclitics and clitic combinations may require harder computation. These results allow us to conclude that if an individual or a population has issues on single DO and IO clitics with finite verbs, they will have issues with all other instances in the assessment. If an individual or a population shows no issues on single DO and IO clitics with finite verbs, they show typical language. In this, single clitics are coherent to their role of clinical markers. However, this study highlights the power of other instances of clitics, namely enclitics and clitic combinations, to unearth vulnerabilities to complex language. Types of non-target response also showed to be in part characterizing of different populations. The most striking result in this sense is the production of a lexical NP in place of the clitic. In typical development, this answer type only becomes the most used alternative answer in the hardest constructions, namely in enclisis; on the other hand, heritage speakers systematically use this construction as the alternative to clitics and use it more than they use clitics across all conditions. In our results, errors that are usually associated with impairment, particularly in younger participants, were marginally present in all groups. These are errors on the φ-features of the clitics, omissions, and misplacements (of which we found no instances), and they were limited to the youngest TD group, the heritage speakers, and the lowest-performing ASD participant. A recurrent alternative structure employed in conditions eliciting enclitics was the production of a simplified, finite verb structure.

L’obésité de l’enfant et de l’adolescent constitue un problème de santé publique important auquel sont confrontés depuis les années 1970 tous les pays industrialisés. Son origine multifactorielle, l’absence de médicaments présentant une balance bénéfice/risque favorable et l’absence de recommandations quant à la chirurgie bariatrique en font un problème thérapeutique complexe. Ceci a induit une grande variété de prises en charge thérapeutiques dont la comparaison reste difficile en absence de critère permettant de juger de leur efficacité. Ce travail avait pour but de déterminer l’efficacité d’une prise en charge multidisciplinaire dans le Centre « Les Oiseaux » pendant 8 mois, en hospitalisation complète. Une étude rétrospective incluant 1063 patients entre 1991 et 2007 a été réalisée. 746 sujets ont retourné le questionnaire 2 ans après leur sortie et 185 sujets, 5 ans après. Parmi eux plus de 75 % ont maintenu durablement au moins la moitié de leur perte de poids.Dans le but de retrouver des marqueurs précoces d’efficacité thérapeutique, nous avons aussi suivi une cohorte de 16 adolescentes et mis en place un programme de monitorage de 895 variables, données cliniques, psychologiques et biologiques ainsi que des données de pratique d’activité physique. Chaque variable a été testée pour son caractère discriminant et sa faisabilité. Une approche de métabolomique par empreintes a été mise en place sur des échantillons urinaires. Par analyse multivariée, nous avons pu montrer que le maintien 6 mois après la sortie, de la perte de poids était positivement corrélé avec la prise en charge psychologique, l’implication familiale et la capacité de conserver une activité physique suffisante, elle même sous-tendue par l’amélioration de l’estime de soi. / Obesity in childhood must be considered as a major issue in Public Health. Since the 1970s, all developed countries must have faced an increasing prevalence of this metabolic disorder. However since the epidemic of obesity has multifactorial causes, and without the availability of a positive benefit/risk balance for chemical drugs and clear-cut indications for bariatric surgery, it is easy to understand that obesity is a complex issue. This complexity induced different schemes of care the comparison of which is made difficult by the absence of clear criteria for judging therapeutic efficacy. This work was aimed to determine the efficacy of a 8-months residential treatment program performed by a multidisciplinary team in the Care Centre “Les Oiseaux”. In order to demonstrate whether the treatment was of benefit for the patients, 1063 of those treated between 1991 and 2007 have been included in a retrospective study. 746 patients returned the questionnaire after 2 years and 185 patients, 5 years later. Among these patients 75 % were actually able to control their weight since they maintained at least half their weight loss. To unveil early parameters of therapeutic efficacy, we have set up a monitoring record of more than 895 clinical, psychological, and biological parameters as well as an accurate recording of the physical activity of adolescents during their stay in the Care Centre. In addition a metabolic profiling of urine samples has been performed. Each parameter was tested for its discrepancy power as well as its practical aspects. Sixteen female adolescents have then been followed for the duration of their stay according to our monitoring program. By multivariate analysis, we deduced that the maintaining of their weight loss was positively correlated with the psychological care, the family involvement, as well as the ability to keep a sufficient physical activity, which was sustained by the recovery of their self-esteem.

In-patient deterioration is a global phenomena and timely recognition and action improves outcome. Intensive care facilities are scarce and expensive and therefore patient care must be optimal. A retrospective health record analysis was used for this study. The findings indicated that nursing personnel do not recognize patient deterioration timeuously. However, the implementation of an outreach team and clinical markers training program improved the recognition of patient deterioration in general wards with three hours and 40 minutes. It is recommended to implement a comprehensive hospital program that addresses the basic knowledge and skills of general ward personnel to observe, recognize, assess and intervene to patients with clinical deterioration. Together with an extensive training program, a basic physiological parameters guideline to activate a team of experts to the bedside, such as an Outreach team, assist nursing personnel to recognize and manage those patients timeuously and ensure treatment in an appropriate level of care. / Health Studies / M. A. (Health studies)

Type 2 diabetes is a significant health problem because of its high prevalence and strong association with cardiovascular morbidity and mortality. An increase of type 2 diabetes is predicted due to increasing obesity and sedentary lifestyle habits. The development from latent to diagnostic disease spans many years and during this time it is possible to prevent or postpone type 2 diabetes using lifestyle and pharmacological interventions. The objective of this thesis is to investigate and describe early patterns and risk indicators of type 2 diabetes. The focus is on type 2 diabetes as one component in metabolic syndrome, i.e. the clustering of several cardiovascular risk markers. Two studies based on the Västerbotten Intervention Programme (VIP) provided the data; one case-referent study nested within VIP which includes 237 diabetes cases that were clinically diagnosed 5.4 years after the health survey, each with two referents; and one panel study with 5 consecutive annual cohorts including subjects that participated in VIP between1990 and 1994 and returned to a follow-up after 10 years, a total of 16 492 individuals. Associations between risk markers and type 2 diabetes or metabolic syndrome are evaluated by several statistical techniques. A model of metabolic syndrome is hypothesized. A prediction model for developing type 2 diabetes among middle-aged individuals is proposed, where high risk is defined as having at least two out of three risk criteria (fasting plasma glucose ≥6.1 mmol/L, HbA1c ≥4.7% (Swedish Mono-S standard) and BMI ≥27 in men and BMI ≥30 in women). With positive predictive values of 32% in men and 46% in women, this model performs at least as well as other published prediction models. Information on family history of diabetes does not improve the result and the cumbersome oral glucose tolerance test is not needed. Therefore this model should be feasible for use in routine care. A model of metabolic syndrome with five composite factors, based on 14 variables including markers produced by adipose tissue and b-cells, suggest that obesity with insulin resistance and b-cell decompensation are the core perturbations in the early stages of type 2 diabetes, while inflammation and dyslipidemia could not be shown to be independent early risk indicators. The composite factors do not improve the prediction as compared to the single markers of fasting glucose, BMI and proinsulin and, possibly blood pressure values. Stress (measured as passive or tense working conditions) and weak social support (measured as emotional support), are suggested to be strong risk indicators along with high BMI for type 2 diabetes in women. In men BMI is predictive, but the stress variables are not shown to be associated with future type 2 diabetes. A social gap is indicated by double risk of metabolic syndrome among subjects with low (≤ 9 years at school) compared to high education (≥ 13 years). High consumption of Swedish smokeless tobacco, snuff (>4 cans/week), is independently associated with metabolic syndrome, obesity and hypertriglyceridemia, but not with dysregulation of glucose. To conclude, single markers, that are commonly used in daily practice, are useful and sufficient for identification of subjects that are in the early stages of type 2 diabetes. Obesity with insulin resistance and b-cell decompensation are the core perturbations in early development to T2DM. Lifestyle, socioeconomic and psychosocial markers, in addition to biomarkers, are important determinants of future type 2 diabetes and metabolic syndrome, albeit not similarly among men and women.

In-patient deterioration is a global phenomena and timely recognition and action improves outcome. Intensive care facilities are scarce and expensive and therefore patient care must be optimal. A retrospective health record analysis was used for this study. The findings indicated that nursing personnel do not recognize patient deterioration timeuously. However, the implementation of an outreach team and clinical markers training program improved the recognition of patient deterioration in general wards with three hours and 40 minutes. It is recommended to implement a comprehensive hospital program that addresses the basic knowledge and skills of general ward personnel to observe, recognize, assess and intervene to patients with clinical deterioration. Together with an extensive training program, a basic physiological parameters guideline to activate a team of experts to the bedside, such as an Outreach team, assist nursing personnel to recognize and manage those patients timeuously and ensure treatment in an appropriate level of care. / Health Studies / M. A. (Health studies)

Background Coronavirus Disease-2019 (COVID-19) affected elderly individuals disproportionately in terms of hospitalization and adverse outcome. Objective This cross-sectional study examined the associations of COVID-19 diagnosis (COVID-negative versus COVID-positive) with levels of four clinical markers – cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), D-dimer and b-type natriuretic peptide (NT-proBNP) – along with potential differences in associations by sex in a hospital-based sample of elderly individuals. Methods The sample comprised individuals aged ≥80 years visiting the Emergency at Karolinska universitetssjukhuset (Huddinge) between January 2020 and December 2021 for whom data on polymerase chain reaction-based COVID-19 testing were available (n=2668). Plasma levels of the markers were measured using standard methods. Right skewed outcome variables were natural-log (Ln) transformed. Multivariable linear regression models were fitted. Results Participants’ median age was 87 years (interquartile range: 85–90) and 58.4% were female. Approximately 13% of the participants were COVID-19 positive. There was no statistically significant association between COVID-positive diagnosis and any of the markers after controlling for age and sex. On sex stratification, COVID-19 positive males had 55.3% (95% confidence interval (CI): 1.1%–138.4%; P=0.044) higher hsCRP levels than COVID-negative males. Additionally, age was positively associated with cTnT (Ln cTnT βadjusted: 0.041; 95% CI: 0.033–0.050; P<0.001) and NT-proBNP (Ln NTproBNP βadjusted: 0.059; 95% CI: 0.015–0.102; P=0.008). Conclusion COVID-positive diagnosis was not related with the markers apart from a sex-specific, positive association with hsCRP observed among males. Future studies should explore the relationship of these markers with mortality to determine their prognostic utility among elderly individuals.