The effects of centrally acting ACE inhibitors on the rate of cognitive and functional decline in dementia: a KDD approach

Alzheimer’s Disease and other dementias are one of the most challenging illnesses confronting countries with ageing populations. Treatment options for dementia are limited, and the costs are significant. There is a growing need to develop new treatments for dementia, especially for the elderly. There is also growing evidence that centrally acting angiotensin converting enzyme (ACE) inhibitors, which cross the blood-brain barrier, are associated with a reduced rate of cognitive and functional decline in dementia, especially in Alzheimer’s disease (AD). The aim of this research is to investigate the effects of centrally acting ACE inhibitors (CACE-Is) on the rate of cognitive and functional decline in dementia, using a three phased KDD process. KDD, as a scientific way to process and analysis clinical data, is used to find useful insights from a variety of clinical databases. The data used are from three clinic databases: Geriatric Assessment Tool (GAT), the Doxycycline and Rifampin for Alzheimer’s Disease (DARAD), and the Qmci validation databases, which were derived from several different geriatric clinics in Canada. This research involves patients diagnosed with AD, vascular or mixed dementia only. Patients were included if baseline and end-point (at least six months apart) Standardised Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) or Activities Daily Living (ADL) scores were available. Basically, the rates of change are compared between patients taking CACE-Is, and those not currently treated with CACE-Is. The results suggest that there is a statistically significant difference in the rate of decline in cognitive and functional scores between CACE-I and NoCACE-I patients. This research also validates that the Qmci, a new short assessment test, has potential to replace the current popular screening tests for cognition in the clinic and clinical trials.

Joint Analysis of Multiple Algorithms and Performance Measures

There has been an increasing interest in the development of new methods using Pareto optimality to deal with multi-objective criteria (for example, accuracy and time complexity). Once one has developed an approach to a problem of interest, the problem is then how to compare it with the state of art. In machine learning, algorithms are typically evaluated by comparing their performance on different data sets by means of statistical tests. Standard tests used for this purpose are able to consider jointly neither performance measures nor multiple competitors at once. The aim of this paper is to resolve these issues by developing statistical procedures that are able to account for multiple competing measures at the same time and to compare multiple algorithms altogether. In particular, we develop two tests: a frequentist procedure based on the generalized likelihood-ratio test and a Bayesian procedure based on a multinomial-Dirichlet conjugate model. We further extend them by discovering conditional independences among measures to reduce the number of parameters of such models, as usually the number of studied cases is very reduced in such comparisons. Data from a comparison among general purpose classifiers is used to show a practical application of our tests.

Fishers’ perception on livelihood strategies, adaptation and mitigation measures to cope with changes in climate variables around Lake Wamala, Uganda

Fisheries support livelihoods but are threatened by climate variability and change which intensified since the 1970s. This study used quantitative and qualitative methods to determine the extent to which fishers around Lake Wamala in Uganda were copying with perceived changes in climate variables and the impacts on their livelihoods, to generate knowledge to enable the fishers increase resilience and sustain their livelihoods. Fishers were aware of changes in climate manifested by unpredictable seasons, floods and droughts. Fishing was the main livelihood activity. The African catfish had replaced Nile tilapia as the dominant fish species. There was damage and loss of gear, boats, landing sites and lives, and changes in fish catches and sizes, income and fish consumption during the perceived floods and droughts. The fishers adapted to the changes through increasing time on fishing grounds and changing target species and fishing gears but innovative ones diversified to high value crops and livestock which increased their income beyond what was earned from fishing thus acting as an incentive for some of them to quit fishing. Diversification to non-fishery activities as a form of adaptation was enhanced by membership to social groups, weekly fishing days, fishing experience and age of fishers but its benefits were not equally shared among men and women. Mitigation measures included planting trees, mulching gardens and protecting wetlands. Adaptation and mitigation measures were constrained by limited credit, awareness and land. The required interventions included improving access to credit, irrigation facilities and appropriate planting materials and raising awareness. The study showed that the fishers were aware of changes in climatic variables and the impacts on their livelihoods. There were also adaptation and mitigation measures practiced by the fishers which if promoted and their constraints addressed, could increase resilience of fishers to climatic change and sustain their livelihoods.

THE RELATIVE SIGNIFICANCE OF SYNTACTIC KNOWLEDGE AND VOCABULARY KNOWLEDGE IN SECOND LANGUAGE LISTENING COMPREHENSION

The main purpose of the current study was to examine the role of vocabulary knowledge (VK) and syntactic knowledge (SK) in L2 listening comprehension, as well as their relative significance. Unlike previous studies, the current project employed assessment tasks to measure aural and proceduralized VK and SK. In terms of VK, to avoid under-representing the construct, measures of both breadth (VB) and depth (VD) were included. Additionally, the current study examined the role of VK and SK by accounting for individual differences in two important cognitive factors in L2 listening: metacognitive knowledge (MK) and working memory (WM). Also, to explore the role of VK and SK more fully, the current study accounted for the negative impact of anxiety on WM and L2 listening. The study was carried out in an English as a Foreign Language (EFL) context, and participants were 263 Iranian learners at a wide range of English proficiency from lower-intermediate to advanced. Participants took a battery of ten linguistic, cognitive and affective measures. Then, the collected data were subjected to several preliminary analyses, but structural equation modeling (SEM) was then used as the primary analysis method to answer the study research questions. Results of the preliminary analyses revealed that MK and WM were significant predictors of L2 listening ability; thus, they were kept in the main SEM analyses. The significant role of WM was only observed when the negative effect of anxiety on WM was accounted for. Preliminary analyses also showed that VB and VD were not distinct measures of VK. However, the results also showed that if VB and VD were considered separate, VD was a better predictor of L2 listening success. The main analyses of the current study revealed a significant role for both VK and SK in explaining success in L2 listening comprehension, which differs from findings from previous empirical studies. However, SEM analysis did not reveal a statistically significant difference in terms of the predictive power of the two linguistic factors. Descriptive results of the SEM analysis, along with results from regression analysis, indicated to a more significant role for VK.

Cognitive and structural aspects of addiction: Relation between iris patterns, time perception, eyeblink rate, impulsivity and cigarette addiction

Objectif : Le but de ce travail est d'étudier les corrélations existantes entre les patterns de l'iris, la perception du temps et la fréquence de clignement des paupières (eye blink rate) et ceci en relation avec l'addiction à la cigarette. Méthodologie: Revue de la littérature existante. Expériences sur une cohorte d'au moins trente sujets fumeurs/non-fumeurs. Analyses statistiques. Résultats: Nos résultats confirment qu'il existe des relations entre l'impulsivité, les patterns d'iris, l'eye blink rate spontané et la perception du temps. Nous observons également que l'addiction à la cigarette et son niveau de dépendance ont une influence sur ces différentes mesures. En effet, les sujets fumeurs tendent à avoir une personnalité plus impulsive par rapport aux sujets contrôles. On remarque également une nette diminution de l'eye blink rate dans le groupe des fumeurs et une tendance à la sur-estimation du temps qui passe. Conclusion : Ce travail nous permet de mieux comprendre les différentes corrélations qui existent entre les différentes variables que nous avons mesurées (patterns d'iris, score d'impulsivité et eye blink rate) ainsi que leur relation à l'addiction à la cigarette. Dès lors qu'il est avéré que les fumeurs peuvent avoir une perception du temps altérée par rapport au groupe contrôle, il serait intéressant d'en étudier l'évolution sur le long terme (aggravation avec la durée du tabagisme actif) ainsi que les conséquences qui en découlent écologiquement au moyen d'études longitudinales et de terrain.

Indigofera tinctoria Linn (Fabaceae) attenuates cognitive and behavioral deficits in scopolamine-induced amnesic mice

Purpose: To investigate the cognition-enhancing effects of aqueous extract of Indigofera tinctoria Linn (ITE, Fabaceae) in experimental amnesic mice. Methods: Scopolamine (2 mg/kg, i.p.) was used to induce amnesia in mice. The cognitive-enhancing activity of the ITE (5, 10 and 20 μg/mL) was studied by passive avoidance response, elevated plus maze and Y-maze behavioral paradigm in normal and scopolamine-induced amnesic mice. Antioxidant activities were also determined based on the ability of ITE to inhibit lipid peroxide, superoxide and hydroxyl radicals. Results: Scopolamine-induced cognitive deficits were significantly reversed by ITE (p < 0.001 at 20 mg/kg) in a dose-dependent fashion in all the behavioral paradigms tested. Furthermore, ITE dosedependently scavenged lipid peroxide, superoxide and hydroxyl free radicals with 50 % inhibition concentration (IC50) of 7.28 ± 0.37, 5.25 ± 0.28 and 7.62 ± 0.43 μg/mL, respectively. Conclusion: ITE possesses cognitive-enhancing properties in amnesic mice due to its potent antioxidant action.

Funtional Near Infrared Spectroscopy Study of Language, Joint Attention and Motor Skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Skeletal maturation, fundamental motor skills and motor coordination in children 7–10 years

info:eu-repo/semantics/publishedVersion

Skeletal maturation, fundamental motor skills and motor coordination in children 7–10 years

info:eu-repo/semantics/publishedVersion

Relationships between residual intake and gain, performance, feeding behavior and body measures in Brahman young bulls

2016

Assessing the state of Nephrops norvegicus and management measures in the Central Adriatic Sea

Nephrops norvegicus is a sedentary bottom-dwelling crustacean that represents one of the main commercial species exploited in the Adriatic Sea (Central Mediterranean). An evaluation of the status of this important resource is thus extremely important in order to manage it in a sustainable way. The evaluation of N. norvegicus is complicated by several issues, mainly: (i) the complex biology and behaviour of the species itself, (ii) the presence of subpopulations with different biological traits within the same stock unit. Relevant concentration of N.norvegicus occurs within the Pomo/Jabuka Pits area which is characterised by peculiar oceanographic and geophysical conditions. This area represented for a long time an important fishing ground shared by Italian and Croatian fleets and recently a Fishery Restricted Area (FRA) was established there. The aim of the present study is to perform for the first time an evaluation of the status of the N.norvegicus subpopulation inhabiting the Pomo/Jabuka Pits also accounting for the possible effects on it of the management measures. To achieve this, the principal fisheryindependent and fishery-dependent dataset available for the study area were firstly analysed and then treated. Data collected by the CNR-IRBIM of Ancona through both indirect (“UWTV”) and direct (trawling) methods were refined by means of a revision of the time series and related biases, and a modelling approach accounting for environmental and fishery effects, respectively. Commercial data for both Italy and Croatia were treated in order to obtain landings and length distributions for the Pomo area only; an historical reconstruction of data starting from 1970 was carried out for both countries. The obtained information was used as input for a Bayesian length-based stock assessment model developed through the CASAL software; the flexibility of this model is recommended for N.norvegicus and similar species allowing to deal with sex- and fleet-based integrated assessment method

The Financial Services Regime in International Economic Law: on the Difficult Relationship between Trade Liberalization and Prudential Measures

The PhD thesis analyses the financial services regime in international economic law from the perspective of the difficult relationship between trade liberalisation and prudential measures. Financial stability plays a fundamental role for the well-being and well-functioning of the global economy, but, it is at the same time a complex sector to regulate and supervise and, especially after the 2007-08 economic crisis, States have tightened up their regulation of financial services, introducing more severe and protectionist prudential measures. However, in an increasingly interconnected global economy, the harmonization of prudential regulation at the international level is an essential step to guarantee integrity, fairness and stability of financial markets and trade. The research analyses the tools at disposition to achieve this aim, the related problematic issues and the perspectives and possible solutions for the future, starting from the World Trade Organization (WTO) legal framework and its General Agreement on Trade in Services (GATS), devoted to discipline trade in services among the WTO Members. Then, the research moves to a second legal instrument, the Free Trade Agreements (FTAs), which has witnessed a remarkable spread in the last decades. Finally, the research addresses the international standards, developed by supranational entities and implemented by an increasing number of States, as they offer rules and guidelines adequate to update the international financial scenario. Nevertheless, the international standards alone cannot be the solution because, first, they are not mandatory, as governments decide voluntarily to apply them and, second, their decision-making process do not respect the requirements of transparency and representative membership. In light of this analysis, the thesis aims at providing an answer to its research question: how to give more certainty to States and economic operators in the planning of the domestic disciplines and business activities in order to provide a sound and stable international financial system.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson`s disease

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson`s disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

A parent-completed developmental questionnaire: Follow up of ex-premature infants

Objective: premature infants are at increased risk of developmental disability. Early identification of problems allows intervention to ameliorate or attenuate problems. A reliable screening tool allows triage of children in this high-risk population by identifying those unlikely to need full developmental assessment. To explore the test characteristics of an established parent-completed developmental assessment questionnaire 'Ages and Stages Questionnaire' (ASQ) in follow up of an Australian population of premature infants. Methodology: One hundred and sixty-seven children born prematurely with corrected ages 12- to 48-months attending the Growth and Development Clinic at the Mater Children's Hospital in Brisbane, Queensland, Australia; 136 questionnaires 'ASQ' were returned completed (81%) and were compared to formal psychometric assessment (Griffith Mental Development Scales for 12- and 24-months, Bayley Mental Development Intelligence Scale for 18-months, McCarthy General Cognitive Intelligence Scale for 18-months). Developmental delay was considered to be present if any of the above psychometric assessments fell below 1.0 standard deviations (SD). The ASQ cut-off used was 2.0 SD (US data derived means and SD). Results: Aggregate results for all age groups comparing ASQ to psychometric assessments as 'gold standards' found the ASQ to have the following test characteristics: sensitivity (90%); specificity (77%); positive predictive value (40%); negative predictive value (98%): % over-referred (20%); % under-referred (1%); % agreement (79%). likelihood ratio for children failing the ASQ was 3.8 and for passing the ASQ was 0.13. Twenty-one children with known disabilities were included in the study and in 14 of these, the ASQ overall score agreed with the psychometric assessment (67%). Conclusion: The high negative predictive value of the ASQ supports its use as a screening tool for cognitive and motor delays in the follow up of ex-premature infants. This would need to be combined with other strategies as part of a comprehensive follow up program for ex-premature infants.

Effect of functional gain on satisfaction with medical rehabilitation after stroke

Objective: To examine the association between gain in motor and cognitive functional status with patient satisfaction 3-6 mo after rehabilitation discharge. Design: Patient satisfaction and changes in functional status were examined in 18,375 patients with stroke who received inpatient medical rehabilitation. Information was obtained from 144 hospitals and rehabilitation facilities contributing records to the Uniform Data System for Medical Rehabilitation and the National Follow-up Services. Results: Data analysis revealed significant (P < 0.05) differences in satisfaction responses based on whether information was collected from patient self-report or from a family member proxy, and the two subsets were analyzed separately. Logistic regression revealed the following significant predictors of satisfaction for data collected from stroke patients: cognitive and motor gain, rehospitalization, who the patient was living with at follow-up, age, and follow-up therapy. In the patient-reported data subset, compared with patients who showed improved cognitive or motor functional status, those with no change, respectively, had a 31% and 33% reduced risk of dissatisfaction. In addition, rehospitalized patients had a higher risk of dissatisfaction. For the proxy reported data subset, significant influences on satisfaction were health maintenance, rehospitalization, stroke type, ethnicity, cognitive FIM(TM) gain, length of stay, and follow-up therapy. Conclusions: Ratings of satisfaction with rehabilitation services were affected by change in functional status and whether the information was collected from patient rating or proxy response.