The Role of Obsessive Beliefs and Inferential Confusion in Predicting Treatment Outcomes for Different Subtypes of Obsessive-Compulsive Disorder

Essai doctoral d’intégration Présenté en vue de l’obtention du doctorat (D.Psy.)

Treatment of written verb and written sentence production in an individual with aphasia: A clinical study

Background: Although the efficacy of treatments for spoken verb and sentence production deficits in aphasia has been documented widely, less is known about interventions for written verb and written sentence production deficits. Aims: This study documents a treatment aiming to improve production of (a) written subject-verb sentences (involving intransitive verbs) and (b) written subject-verb-object sentences (involving transitive verbs). Methods & Procedures: The participant, a 63-year-old female aphasic speaker, had a marked language comprehension deficit, apraxia of speech, relatively good spelling abilities, and no hemiplegia. The treatment involved intransitive verbs producing subject-verb active sentences and transitive verbs producing subject-verb-object active non-reversible sentences. The treatment was undertaken in the context of current UK clinical practice. Outcomes & Results: Statistical improvements were noted for the trained sets of verbs and sentences. Other improvements were also noted in LW's ability to retrieve some non-treated verbs and construct written sentences. Treatment did not generalise to sentence comprehension and letter spelling to dictation. Conclusions: Our participant's ability to write verbs and sentences improved as a result of the treatment.

Seeds of growth? Agricultural productivity and the transitional dynamics of the Ramsey model

A two-sector Ramsey-type model of growth is developed to investigate the relationship between agricultural productivity and economy-wide growth. The framework takes into account the peculiarities of agriculture both in production ( reliance on a fixed natural resource base) and in consumption (life-sustaining role and low income elasticity of food demand). The transitional dynamics of the model establish that when preferences respect Engel's law, the level and growth rate of agricultural productivity influence the speed of capital accumulation. A calibration exercise shows that a small difference in agricultural productivity has drastic implications for the rate and pattern of growth of the economy. Hence, low agricultural productivity can form a bottleneck limiting growth, because high food prices result in a low saving rate.

The effect of chlortetracycline treatment and its subsequent withdrawal on multi-resistant Salmonella enterica serovar Typhimurium DT104 and commensal Escherichia coli in the pig

Aims: To investigate the effect of a therapeutic and sub-therapeutic chlortetracycline treatment on tetracyclineresistant Salmonella enterica serovar Typhimurium DT104 and on the commensal Escherichia coli in pig. Methods and Results: Salmonella Typhimurium DT104 was orally administered in all pigs prior to antibiotic treatment, and monitored with the native E. coli. Higher numbers of S. Typhimurium DT104 were shed from treated pigs than untreated pigs. This lasted up to 6 weeks post-treatment in the high-dose group. In this group, there was a 30% increase in E. coli with a chlortetracycline minimal inhibitory concentration (MIC) > 16 mg l(-1) and a 10% increase in E. coli with an MIC > 50 mg l(-1) during and 2 weeks post-treatment. This effect was less-pronounced in the low-dose group. PCR identified the predominant tetracycline resistance genes in the E. coli as tetA, tetB and tetC. The concentration of chlortetracycline in the pig faeces was measured by HPLC and levels reached 80 mug g(-1) faeces during treatment. Conclusion: Chlortetracycline treatment increases the proportion of resistant enteric bacteria beyond the current withdrawal time. Significance and Impact of the Study: Treated pigs are more likely to enter abattoirs with higher levels of resistant bacteria than untreated pigs promoting the risk of these moving up the food chain and infecting man.

Life at university with Asperger syndrome: a comparison of student and staff perspectives

Although increasing numbers of students with disabilities are accessing higher education, there is relatively little information about the needs of students with Asperger syndrome. Crucially, students themselves have rarely been included in research examining their needs or the supports they might find helpful. Three focus groups, one with students with Asperger syndrome and two with staff were conducted to explore the challenges, barriers and supports to students’ successful progress though one university in the UK. Thematic analysis revealed some key differences between staff and student perspectives, particularly with regard to impact of sensory sensitivities and daily life difficulties on academic progress. Students and staff also held differing views about what is helpful, relating to disclosure of diagnosis and the value of formal social supports. The study highlights the importance of developing services beyond traditional academic supports that students with Asperger syndrome themselves feel are valuable.

Urban retrofitting: identifying disruptive and sustaining technologies using performative and foresight techniques

Cities, which are now inhabited by a majority of the world's population, are not only an important source of global environmental and resource depletion problems, but can also act as important centres of technological innovation and social learning in the continuing quest for a low carbon future. Planning and managing large-scale transitions in cities to deal with these pressures require an understanding of urban retrofitting at city scale. In this context performative techniques (such as backcasting and roadmapping) can provide valuable tools for helping cities develop a strategic view of the future. However, it is also important to identify ‘disruptive’ and ‘sustaining’ technologies which may contribute to city-based sustainability transitions. This paper presents research findings from the EPSRC Retrofit 2050 project, and explores the relationship between technology roadmaps and transition theory literature, highlighting the research gaps at urban/city level. The paper develops a research methodology to describe the development of three guiding visions for city-regional retrofit futures, and identifies key sustaining and disruptive technologies at city scale within these visions using foresight (horizon scanning) techniques. The implications of the research for city-based transition studies and related methodologies are discussed.

"Just as fragments are part of a vessel": a translation into medieval Occitan of the life of Alexander the Great

This article examines a 14th-c. translation into Old Occitan prose of a late-antique life of Alexander the Great: Justin’s Epitome of the 'Historia Philippicae' of Pompeius Trogus. The article argues that it is the work of translators whose knowledge of pagan Latin materials was incomplete and whose use of their native tongue rested on non-literary bases. This text has not been edited before, and examining its uneven treatment of its source provides important new insights into the work of translators in the later Middle Ages. In conclusion, the article suggests some new approaches to the understanding of translation as a process of reconstruction and adaptation.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

The specific role of relationship life events in the onset of depression during pregnancy and the postpartum

Background The precipitating role of life events in the onset of depression is well-established. The present study sought to examine whether life events hypothesised to be personally salient would be more strongly associated with depression than other life events. In a sample of women making the first transition to parenthood, we hypothesised that negative events related to the partner relationship would be particularly salient and thus more strongly predictive of depression than other events. Methods A community-based sample of 316 first-time mothers stratified by psychosocial risk completed interviews at 32 weeks gestation and 29 weeks postpartum to assess dated occurrence of life events and depression onsets from conception to 29 weeks postpartum. Complete data was available from 273 (86.4%). Cox proportional hazards regression was used to examine risk for onset of depression in the 6 months following a relationship event versus other events, after accounting for past history of depression and other potential confounders. Results 52 women (19.0%) experienced an onset of depression between conception and 6 months postpartum. Both relationship events (Hazard Ratio = 2.1, p = .001) and other life events (Hazard Ratio = 1.3, p = .020) were associated with increased risk for depression onset; however, relationship events showed a significantly greater risk for depression than did other life events (p = .044). Conclusions The results are consistent with the hypothesis that personally salient events are more predictive of depression onset than other events. Further, they indicate the clinical significance of events related to the partner relationship during pregnancy and the postpartum.

Cone-beam computerized tomographic, radiographic, and histologic evaluation of periapical repair in dogs` post-endodontic treatment

Objective. To evaluate the periapical repair after root canal treatment in the teeth of dogs using CT and conventional radiography and to compare these findings with the gold standard microscopic evaluation. Study design. The animals were divided into three groups according to endodontic treatment performed: Group 1, single-visit endodontic treatment in teeth without apical periodontitis; Group 2, single-visit endodontic treatment in teeth with apical periodontitis; and Group 3, endodontic treatment in teeth with apical periodontitis using calcium hydroxide as a root canal dressing. Group 4 consisted of teeth with apical periodontitis not submitted to root canal treatment and Group 5 consisted of healthy teeth without periapical disease. Radiographic, tomographic, and microscopic evaluations were performed by blind examiners. At 180 days experimental time, CT and radiographic measurements of periapical disease were compared with the gold standard microscopic measurement using intraclass correlation coefficient. Intergroup comparisons considering different methods of periapical lesions measurement or different clinical protocols of root canal treatment were performed by Kruskal Wallis test followed by Dunn. Integrity of lamina dura, presence of radiolucent areas, and presence of root resorption were analyzed by Fisher`s exact test. Results. There was discontinuity of the lamina dura and CPD in all teeth from Groups 2, 3, and 4 evaluated by tomography and radiography 45 days after CPD induction. Radiographically, 180 days after root canal treatment, there was no periapical lesion in teeth from Groups 1 and 3, different from groups 2 and 4 (p < .05). The highest reduction in the CPD size was observed on Group 3 (p < .05). According to the tomographic results, there was decrease of the size of the CPD on Group 3 but not on Groups 2 or 4. However, in all groups the periapical lesions presented larger mesio-distal extension if compared with radiography, both 45 days after CPD induction and 180 days after root canal treatment. At 180 days, CT measurements were closely related to microscopic results (ICC = 0.95) differently from radiographic evaluation (ICC = 0.86). Conclusion. CT Scan evaluation of periapical repair following root canal treatment provided similar information than that obtained by microscopic analysis, whereas radiographic evaluation underestimated the size do periapical lesion. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108:796-805)

Micronutrient prenatal supplementation prevents the development of hypertension and vascular endothelial damage induced by intrauterine malnutrition

Aims: The premise that intrauterine malnutrition plays an important role in the development of cardiovascular and renal diseases implies that these disorders can be programmed during fetal life. Here, we analyzed the hypothesis that supplementation with mixed antioxidant vitamins and essential mineral in early life could prevent later elevation of blood pressure and vascular and renal dysfunction associated with intrauterine malnutrition. Main methods: For this, female Wistar rats were randomly divided into three groups on day 1 of pregnancy: control fed standard chow ad libitum; restricted group fed 50% of the ad libitum intake and a restricted plus micronutrient cocktail group treated daily with a combination of micronutrient (selenium, folate, vitamin C and vitamin E) by oral gavage. Key findings: In adult offspring, renal function and glomerular number were impaired by intrauterine malnutrition. and the prenatal micronutrient treatment did not prevent it. However, increased blood pressure and reduced endothelium-dependent vasodilation were prevented by the micronutrient prenatal treatment. Intrauterine malnutrition also led to reduced NO production associated with increased superoxide generation, and these parameters were fully normalized by this prenatal treatment. Significance: Our current findings indicate that programming alterations during fetal life can be prevented by interventions during the prenatal period, and that disturbance in availability of both antioxidant vitamins and mineral may play a crucial role in determining the occurrence of long-term cardiovascular injury. (C) 2009 Elsevier Inc. All rights reserved.

NUCEL (Cell and Molecular Therapy Center): A multidisciplinary center for translational research in Brazil

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil`s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the Sao Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.

Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment

This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats. (C) 2005 Elsevier B.V. All rights reserved.

Treatment of venous ulcers with fibrin sealant derived from snake venom

Venous ulcers of the lower limbs complicated by infection or chronicity represent a serious public health problem. The elevated number of those afflicted burdens the health services, interferes in quality of life and causes absenteeism. Although there are 2,500 items on the market, ranging from the simplest dressing up to the most complex types of dressing, treatment remains a challenge. Among the substances used, fibrin sealant is the one that promotes diminution of bacterial colonization and of edema, controls hemorrhaging, alters the pain threshold by protecting the nerve endings, hydrates the wound bed and forms granulation tissue that favors healing. Its disadvantages include higher cost and utilization of human fibrinogen that can transmit infectious diseases. The Center for the Study of Venoms and Venomous Animals (CEVAP) at São Paulo State University (UNESP) developed a new sealant made up of fibrinogen extracted from large animals and from an enzyme obtained from snake venom. The present study, developed in the Health Education Clinic (CEPS) of Sacred Heart University (USC) aimed to evaluate the effect of the new sealant on the healing process of venous ulcers in 24 adult patients, seven of whom were male and 17 female. Two study groups were formed as follows: Group 1 (G1) - control group of 11 patients treated with essential fatty acid (EFA) and Unna's boot, and Group 2 (G2) - 13 patients treated with essential fatty acid (EFA), fibrin sealant and Unna's boot. The follow-up lasted eight weeks and the sealant was applied at only the first and fourth weeks. The results showed that Group 2 presented worse lesion conditions as to healing, but, when comparing the two groups, it was noteworthy that the the sealant was effective in healing venous ulcers. There is evidence that the new sealant is recommended for leg ulcers with the following advantages: ease of application, preparation of the wound bed, diminution of pain and a higher number of discharges in the eighth week. More important, other positive characteristics are non-transmission of infectious diseases, absence of adverse reactions, and economic advantage of being produced by Brazilian technology. Finally, it is suggested that the weekly application of sealant, for at least eight weeks, could improve the healing process and consequently life quality.

Cytokines and acute-phase serum proteins as markers of inflammatory regression during pulmonary tuberculosis treatment

Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the World Health Organization (WHO) in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-gamma and TNF-alpha, a central factor in immune response against Mycobacterium tuberculosis, are responsible for the interaction between T lymphocytes and the infected macrophage and are also produced during this interaction. As proinflammatory cytokines have a close relationship with mycobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute-phase response as a result of homeostatic and physiological responses also induced by them. Acute-phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-gamma, TNF-alpha, IL-10 and TGF-beta production in supernatant of peripheral blood mononuclear cell (PBMC) and monocyte (MO) cultures, as well as serum acute-phase response through total protein, albumin, globulin, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (BSM-UH) were evaluated once and 28 pulmonary tuberculosis patients (G2): 13 from BSM-UH and 15 from the Bauru State Health Secretariat. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20ml of peripheral blood (ELISA), with or without activation: lipopolysaccharide (LPS) for MO culture and phytohemagglutinin (PHA) for PBMC culture. Acute-phase protein behavior in G2 throughout treatment was: Globulins: M1> M2, M1> M3 (rho < 0.001); CRP: M1> M2> M3 (.< 0.001); AGP for men: M1> M2, M1> M3 (rho < 0.001); ESR for men: M1> M2, M1> M3 (rho < 0.0016) and for women: M1> M2 (.< 0.025). Comparison between cytokine levels found in supernatant of MO and PBMC cultures, with and without stimulus, in G1 and G2 during treatment showed: TNF-alpha (with/ without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); (without LPS) at M3: G2> G1 (rho < 0.001), (with LPS) at M3: G2> G1 (rho < 0.028); IFN-. (with and without PHA) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); IL-10 (with and without LPS) at M1: G2> G1; at M2: G2> G1; at M3: G2> G1 (rho < 0.001); TGF-beta (with and without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001), (without LPS) at M3: G2> G1 (rho < 0.001). In G2, all cytokines in supernatant of MO and PBMC cultures, with and without stimulus, showed: M1> M2> M3 (rho < 0.01). Levels of globulins, CRP, AGP, and ESR in patients with pulmonary tuberculosis before treatment (M1) were significantly higher than reference values, suggesting their use as diagnostic markers and indicators of treatment. The CRP decreasing values along treatment could be taken as a marker of the regression of inflammatory process and of response to treatment in patients with pulmonary tuberculosis.Regarding cytokines, there was significant increase in TNF-alpha, IFN-gamma, IL-10, and TGF-alpha levels before and at three months treatment, with and without stimulus; in TNF-a and IL-10 lvels, with and without stimulus, as well as in TGF-alpha levels without stimulus at six months. Patients had higher levels of all studied cytokines than controls before treatment, and these values decreased along treatment. In this study, pulmonary tuberculosis patients showed a Th0 cytokine profile before treatment, with the production of both Th1 (IFN-gamma) and Th2 (IL-10) cytokines, in addition to TNF-alpha inflammatory and TGF-alpha regulatory and fibrosis-inducer cytokines. At the end of treatment, all had evolved to Th2 profile, probably in an attempt to reduce the harmful effects of the proinflammatory activity of the Th1 cytokine profile and of the still above-normal levels of TNF-alpha. The high levels of TGF-alpha, also found in these patients, are related to its important role in the extracellular matrix deposition and fibrosis induction that characterize tuberculosis healing process. IFN-gamma was the only cytokine reaching normal levels at the end of treatment, which suggests its use as a marker of response to treatment.