[My Lady Hundon's Puffe]

Soitinnus: kitara.

[Fantasia]

Soitinnus: kitara.

A recital by students of the Sibelius Academy, Finland

Sibelius-Akatemian oppilasvaihtokonsertti Manchesterissa 23.9.1975.

[Elegio de la Danza]

Soitinnus: kitara.

[Melancoly Galliard]

Soitinnus: kitara.

Läheisen rooli ja tuen tarve iäkkään kotiutuessa arviointi- ja kuntoutusosastolta

Tämän tutkimuksen tarkoituksena oli kuvata läheisen roolia ja tuen tarvetta iäkkään kotiutuessa arviointi- ja kuntoutusosastolta. Tavoitteena oli saada tietoa iäkkäiden kotiutusprosessista läheisen näkökulmasta ja muodostaa käsitteellinen malli, jossa on tyypitelty läheisen erilaiset roolit, niihin vaikuttavat tekijät ja tuen tarpeet iäkkään kotiutuessa arviointi- ja kuntoutusosastolta. Tutkimus oli kuvaileva tutkimus, jossa sovellettiin metodologista triangulaatiota. Kotiutuva iäkäs nimesi läheisen (n=14), jolta kerättiin tutkimusaineistoa teemahaastattelulla ja kyselyllä (COPE -indeksi, Carers of Older People in Europe). Rekrytointi tapahtui viidellä arviointi- ja kuntoutusosastolla Etelä-Suomessa kesällä 2015. Teemahaastattelu analysoitiin induktiivisella sisällönanalyysillä ja kyselyn (COPE -indeksi) vastauksista laskettiin prosenttiosuudet ja kolmella osa-alueella laskettiin lisäksi summapisteiden keskiarvot. Tutkimuksen päätulos tuli teemahaastattelun sisällön analyysistä, jota vahvistettiin kyselystä (COPE -indeksi) saaduilla tuloksilla. Tämän tutkimuksen tuloksena syntyi käsitteellinen malli läheisen roolista ja tuen tarpeista iäkkään kotiutuessa arviointi- ja kuntoutusosastolta. Läheisen rooli jakautui neljään päärooliin, jotka olivat iäkkään arjen auttajan rooli, edunvalvojan rooli, tukijan rooli ja vastuunkantajan rooli. Arjen auttajan rooliin kuului läheisen käytännön järjestäjän rooli ja kodinhoitajan rooli. Edunvalvojan rooliin sisältyi iäkkään terveydellinen edunvalvojan rooli, taloudellinen edunvalvojan rooli ja puolestapuhujan rooli. Tukijan rooli muodostui iäkkään virkistäjän roolista ja muutokseen sopeuttajan roolista. Näissä rooleissa toimimiseen vaikuttavia tekijöitä olivat läheisen ja iäkkään välinen suhde, läheisen oma elämä, rooliin saatu tuki ja roolin mielekkyys. Läheisen roolissa tuen tarpeita olivat arjen tuki, roolissa toimimisen tuki, rohkaiseva ja sosiaalinen tuki. Kyselyn (COPE -indeksi) tulokset täydensivät kuvausta läheisen rooliin vaikuttavista tekijöistä ja tuen tarpeista. Keskeistä tuloksissa oli, että läheisillä oli hyvä suhde iäkkäisiin, avustaminen koettiin vaivan arvoiseksi ja muiden ihmisten koettiin arvostavan heidän toimimistaan iäkkään avustajana. Ajoittain avustaminen koettiin liian vaativana tuoden kielteisiä vaikutuksia omaan tunne-elämään ja fyysiseen terveydentilaan, tunnettiin olevan ansassa. Läheiset tunsivat saavansa hyvin tukea perheeltä, mutta sosiaali- ja terveyspalveluista saatavassa tuessa koettiin parannettavaa. Tämän empiirisen tutkimuksen tuloksena tuotettu käsitteellinen malli todentaa läheisen roolin monimutkaisuuden ja moniulotteisuuden. Läheisen roolissa tarvitaan erityistä tukea tilanteiden muuttuessa, kuten kotiutustilanteissa. Tutkimuksen tuloksia voidaan hyödyntää kehitettäessä iäkkäiden yksilöllistä kotiutumista ja tilanteeseen sopivia läheisen roolia tukevia palveluita.

Cholesterol, cardiovascular disease and statin use in older persons

Older age increases the risk of developing a chronic atherosclerotic cardiovascular disease (CVD), such as coronary heart disease. Complications of CVDs, myocardial infarction or stroke often lead to loss of functional capacity or premature death. Dyslipidemia, high serum levels of total or low-density lipoprotein cholesterol (LDL-c) and low levels of high-density lipoprotein cholesterol (HDL-c), is among the most important modifiable risk factors for CVDs; it can be treated with lifestyle modifications, and with lipid-lowering drugs, primarily statins. In older persons, however, the association of cholesterol levels with cardiovascular and all-cause mortality has been inconsistent in previous studies. Furthermore, the beneficial effects of statins in older persons without previous CVD are still somewhat unclear, and older persons are more prone to adverse effects from statins. This thesis presents a prospective cohort study (TUVA), exploring associations of cholesterol levels with mortality and the changes in cholesterol levels of a 70-year-old population in long-term follow-up. Further, prevalence of CVDs, risk factors and preventive medication use in the TUVA cohort is compared with respective prevalences in another age-matched cohort (UTUVA) 20 years later in order to examine the changes in cardiovascular risk over time. Additionally, to evaluate statin use patterns among older persons, an observational register study was conducted covering the total Finnish population aged 70 and older during 2000-2008. Based on individual-level data retrieved from national health registries, the population was classified into low, moderate and high risk groups according to estimated CVD risk. The prevalence, incidence and persistence of statin use among the risk groups was then evaluated based upon yearly statin purchases tracked from the Prescription Register. The prospective cohort study demonstrated that low total cholesterol, LDL-c and HDL-c were associated with higher mortality in a cohort of home-dwelling 70-year-olds. However, after adjusting for traditional cardiovascular risk factors and cancer this association disappeared. Further, low total cholesterol seemed to be protective, whereas low HDL-c strongly predicted increased risk of CVD death. Cholesterol levels of those elderly who remained available for follow-up and were still home-dwelling at the age of 85 seemed to improve with advancing age. Compared to the TUVA cohort, the later born UTUVA cohort had less CVDs and their risk factors were better controlled, which was reflected in the higher use of preventive medications such as statins and antihypertensives. The register studies confirmed that statin use has increased significantly during 2000-2008 among older persons, especially among the oldest (80+) age groups and among those at high risk for cardiovascular events. Two-thirds of new statin users persisted with their use during the four years of follow-up; the most discontinuations were made during the first year of use. In conclusion, statins are commonly used among older age groups in Finland. Most of the older statin users had a high cardiovascular event risk, indicating that the treatment is well directed towards those who are likely to benefit from it the most. No age-limits should be put on the screening and treatment of dyslipidemia in older persons, but the benefits and adverse effects of statin treatment should be carefully weighed based on an individual assessment of the person’s general health status and functional capacity. Physicians should pay more attention to medication adherence, especially when prescribing preventive medications.

Vers une musique numérique vivante : Regard sur le processus créatif de quatre œuvres musicales

La version intégrale de ce mémoire est disponible uniquement pour consultation individuelle à la Bibliothèque de musique de l’Université de Montréal (http://www.bib.umontreal.ca/MU).

Electrolyte disorders in the human ventricle. A simulation study.

Ventricular cells are immersed in a bath of electrolytes and these ions are essential for a healthy heart and a regular rhythm. Maintaining physiological concentration of them is fundamental for reducing arrhythmias and risk of sudden cardiac death, especially in haemodialysis patients and in the heart diseases treatments. Models of electrically activity of the heart based on mathematical formulation are a part of the efforts to improve the understanding and prediction of heart behaviour. Modern models incorporate the extensive and ever increasing amounts of experimental data in incorporating biophysically detailed mechanisms to allow the detailed study of molecular and subcellular mechanisms of heart disease. The goal of this project was to simulate the effects of changes in potassium and calcium concentrations in the extracellular space between experimental data and and a description incorpored into two modern biophysically detailed models (Grandi et al. Model; O’Hara Rudy Model). Moreover the task was to analyze the changes in the ventricular electrical activity, in particular by studying the modifications on the simulated electrocardiographic signal. We used the cellular information obtained by the heart models in order to build a 1D tissue description. The fibre is composed by 165 cells, it is divided in four groups to differentiate the cell types that compound human ventricular tissue. The main results are the following: Grandi et al. (GBP) model is not even able to reproduce the correct action potential profile in hyperkalemia. Data from hospitalized patients indicates that the action potential duration (APD) should be shorter than physiological state but in this model we have the opposite. From the potassium point of view the results obtained by using O’Hara model (ORD) are in agreement with experimental data for the single cell action potential in hypokalemia and hyperkalemia, most of the currents follow the data from literature. In the 1D simulations we were able to reproduce ECGs signal in most the potassium concentrations we selected for this study and we collected data that can help physician in understanding what happens in ventricular cells during electrolyte disorder. However the model fails in the conduction of the stimulus under hyperkalemic conditions. The model emphasized the ECG modifications when the K+ is slightly more than physiological value. In the calcium setting using the ORD model we found an APD shortening in hypocalcaemia and an APD lengthening in hypercalcaemia, i.e. the opposite to experimental observation. This wrong behaviour is kept in one dimensional simulations bringing a longer QT interval in the ECG under higher [Ca2+]o conditions and vice versa. In conclusion it has highlighted that the actual ventricular models present in literature, even if they are useful in the original form, they need an improvement in the sensitivity of these two important electrolytes. We suggest an use of the GBP model with modifications introduced by Carro et al. who understood that the failure of this model is related to the Shannon et al. model (a rabbit model) from which the GBP model was built. The ORD model should be modified in the Ca2+ - dependent IcaL and in the influence of the Iks in the action potential for letting it him produce a correct action potential under different calcium concentrations. In the 1D tissue maybe a heterogeneity setting of intra and extracellular conductances for the different cell types should improve a reproduction of the ECG signal.

Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange– Nielsen Syndrome

KCNQ1 encodes KCNQ1, which belongs to a family of voltage-dependent K+ ion channel proteins. KCNQ1 associates with a regulatory subunit, KCNE1, to produce the cardiac repolarizing current, IKs. Loss-of-function mutations in the human KCNQ1 gene have been linked to Jervell and Lange–Nielsen Syndrome (JLNS), a disorder characterized by profound bilateral deafness and a cardiac phenotype. To generate a mouse model for JLNS, we created a line of transgenic mice that have a targeted disruption in the Kcnq1 gene. Behavioral analysis revealed that the Kcnq1−/− mice are deaf and exhibit a shaker/waltzer phenotype. Histological analysis of the inner ear structures of Kcnq1−/− mice revealed gross morphological anomalies because of the drastic reduction in the volume of endolymph. ECGs recorded from Kcnq1−/− mice demonstrated abnormal T- and P-wave morphologies and prolongation of the QT and JT intervals when measured in vivo, but not in isolated hearts. These changes are indicative of cardiac repolarization defects that appear to be induced by extracardiac signals. Together, these data suggest that Kcnq1−/− mice are a potentially valuable animal model of JLNS.

Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48–72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, IKr, of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed IKr without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, IKs, without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed IKs and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.