Effects of beta-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2

Peer reviewe

Passive neutron albedo reactivity measurements of spent nuclear fuel

The upcoming disposal of spent nuclear fuel in Finland creates new challenges for nuclear safeguards. Part of the national safeguards concept for geological repositories, developed by STUK — Radiation and Nuclear Safety Authority, is non-destructive assay (NDA) verification of all fuel items before disposal. The proposed verification system is a combination of PGET (Passive Gamma Emission Tomography), PNAR (Passive Neutron Albedo Reactivity) and weight measuring NDA-instruments. PGET takes a pin-level image of the fission products inside of a fuel assembly and PNAR verifies the multiplication of the assembly, a quantity that correlates with the fissile content. PGET is approved by IAEA (International Atomic Energy Agency) for safeguards measurements, but the feasibility of PNAR has not yet been established. A first of its kind PNAR prototype instrument was built in a collaboration coordinated by STUK. This paper concludes the results of the first measurements of spent BWR (Boiling Water Reactor) nuclear fuel with the prototype in July 2019. Based on the measurements, the ability of the PNAR instrument to detect the presence of fissile material in a repeatable manner in a reasonable amount of time was demonstrated. Furthermore, the instrument was able to detect differences in multiplication between partially and fully spent fuel assemblies, and axial differences in multiplication within a single assembly.Peer reviewe

Katekoliamiiniherkkä monimuotoinen kammiotakykardia (CPVT) - harvinainen mutta vaarallinen sydänsairaus

Vertaisarvioitu.Katekoliamiiniherkkä monimuotoinen kammiotakykardia (CPVT) on harvinainen mutta vakava perinnöllinen rytmihäiriösairaus, johon liittyy hoitamattomana merkittävä äkkikuoleman riski. Sairauden tunnusomainen piirre on rasituksen aikana ilmaantuva monimuotoinen kammiolisälyöntisyys, vaikka potilaiden lepo-EKG on normaali eikä sydämessä todeta rakenteellisia poikkeavuuksia. Kliininen rasituskoe on keskeinen tutkimus CPVT:n diagnosoinnissa. Syy rytmihäiriöalttiudelle johtuu sydänlihassolujen kalsiumviestintään vaikuttavista mutaatioista, ja geenivirhe pystytään toteamaan noin kahdessa tapauksessa kolmesta. Lähisukulaisten tutkiminen on tärkeää, jotta kaikki sydäntapahtumille alttiit henkilöt saadaan ehkäisevien toimien sekä hoidon piiriin. CPVT-potilaiden tulee välttää raskasta urheilua ja tilanteita, joissa he voivat altistua voimakkaille yllättäville stressitekijöille. Potilaille aloitetaan beetasalpaajahoito, ja valikoiduissa tapauksissa käytetään flekainidia. Pienelle osalle potilaista on aiheen asentaa defibrilloiva rytmihäiriötahdistin.Peer reviewe

Job strain and supervisor support in primary care health centres and glycaemic control among patients with type 2 diabetes: a cross-sectional study

Peer reviewe

Genealogy and clinical course of catecholaminergic polymorphic ventricular tachycardia caused by the ryanodine receptor type 2 P2328S mutation

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD).Aims We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation.Methods The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study. Kaplan-Meier graphs, log-rank test and Cox regression model were used to evaluate the clinical course.Results Genealogical study revealed a common ancestor couple living in the late 17(th) century. A total of 1837 living descendants were tested for RYR2 P2328S mutation unveiling 62 mutation carriers aged mean 3923 years old. No arrhythmic deaths were documented among genotyped subjects, but 11 SCDs were detected in non-genotyped family members since 1970. Three genotyped patients (5%) suffered an aborted cardiac arrest (ACA), and 15 (25%) had a syncope triggered by exercise or stress. Rate of cardiac events was higher among patients who in exercise stress test showed a maximum rate of premature ventricular contractions >30/min (68% vs 17%, p<0.01; hazard ratio = 7.1, p = 0.02), in comparison to patients without the respective finding. A cardioverter-defibrillator (ICD) was implanted to 13 (22%) patients, with an appropriate ICD shock in four (31%) subjects. All ICD shocks, one ACA, and one syncope occurred during -blocker medication.Conclusions Previously undiagnosed CPVT patients may be identified by well-conducted genealogical studies. The RYR2 P2328S mutation causes a potentially severe phenotype, but its expression is variable, thus calling for additional studies on modifying factors

Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients

Background: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving beta-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. Methods: A follow-up study covering a mean of 18.6 +/- 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. Results: In mutation carriers, risk factors for cardiac events before initiation of beta-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p = 500 ms (vs G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c. 453delC, L552S and R176W mutations associated with lower risk (HR = 0.11-0.23, p <0.001) than other KCNH2 mutations. Conclusions: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.Peer reviewe

Feasibility of a controlled trial aiming to prevent excessive pregnancy-related weight gain in primary health care

<p>Abstract</p> <p>Background</p> <p>Excessive gestational weight gain and postpartum weight retention may predispose women to long-term overweight and other health problems. Intervention studies aiming at preventing excessive pregnancy-related weight gain are needed. The feasibility of implementing such a study protocol in primary health care setting was evaluated in this pilot study.</p> <p>Methods</p> <p>A non-randomized controlled trial was conducted in three intervention and three control maternity and child health clinics in primary health care in Finland. Altogether, 132 pregnant and 92 postpartum women and 23 public health nurses (PHN) participated in the study. The intervention consisted of individual counselling on physical activity and diet at five routine visits to a PHN and of an option for supervised group exercise until 37 weeks' gestation or ten months postpartum. The control clinics continued their usual care. The components of the feasibility evaluation were 1) recruitment and participation, 2) completion of data collection, 3) realization of the intervention and 4) the public health nurses' experiences.</p> <p>Results</p> <p>1) The recruitment rate was slower than expected and the recruitment period had to be prolonged from the initially planned three months to six months. The average participation rate of eligible women at study enrolment was 77% and the drop-out rate 15%. 2) In total, 99% of the data on weight, physical activity and diet and 96% of the blood samples were obtained. 3) In the intervention clinics, 98% of the counselling sessions were realized, their contents and average durations were as intended, 87% of participants regularly completed the weekly records for physical activity and diet, and the average participation percentage in the group exercise sessions was 45%. 4) The PHNs regarded the extra training as a major advantage and the high additional workload as a disadvantage of the study.</p> <p>Conclusion</p> <p>The study protocol was mostly feasible to implement, which encourages conducting large trials in comparable settings.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN21512277</p

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.Peer reviewe

Poisson-hajotelma ryhmitellyllä datalla: Sovelluskohteena TV-ohjelmien suosittelu isolla aineistolla

Non-negative matrix factorization models are popular for response prediction in recommender systems. Usually, the predictions are based on the behavioral data of the user population, in which little data is available per user and per recommendable item so that making accurate predictions is difficult. Recommending newly added content is especially hard, and it is referred to as the "cold-start problem". One way to resolve the problem is to incorporate additional metadata into the model, but many of the existing models are hard to extend. This thesis develops a multilevel Poisson factorization model that incorporates the grouping information of items using principles from multilevel modeling. The inference algorithm is conducted with stochastic gradient variational inference so the model can be easily refined and extended further. The model is evaluated with watching behavior data from an online streaming service, where the groupings of items are TV series. The results indicate that the multilevel model improves the predictive accuracy compared to the baseline models within the particular dataset. As the study was conducted on a single dataset alone, further research is needed to be able to generalize the results to different contexts. Finally, the thesis highlights a promising development of generic inference and modeling tools, a development referred to as probabilistic programming. Probabilistic programming makes it easier to explore and incorporate richer probabilistic models for recommender systems.Suosittelujärjestelmät hyödyntävät matriisihajotelmapohjaisia malleja ennustamaan sisällön kulutusta olemassa olevan käyttäytymisdatan perusteella. Usein vain vähän dataa on saatavilla käyttäjää ja sisältöä kohden, mikä vaikeuttaa tarkkojen ennusteiden tekemistä. Etenkin uusi sisältö tuottaa haasteita, koska lyhyessä ajassa havaintoja ei ehdi kertyä tarpeeksi. Yksi ratkaisu parantaa ennusteiden laatua on lisätä käyttäytymisdatan rinnalle muuta metatietoa, mutta nykyisten mallien laajentaminen on usein vaikeaa. Tässä työssä kehitetään monitasoinen Poisson-hajotelma, joka hyödyntää sisällön ryhmittelytietoa todennäköisyysmallissa. Mallin parametrit päätellään stokastisen gradientin variationaalisella päättelyllä, joka mahdollistaa mallin helpon jatkokehityksen ja muokkaamisen. Mallia arvioidaan online-suoratoistopalvelun katseluaineistolla. Tuloksien perusteella malli parantaa suositteluita vertailukohtiin nähden kyseisellä aineistolla. Lisätutkimusta tarvitaan tulosten yleistämiseen muihin konteksteihin. Työ myös korostaa hyötyjä geneerisen päättelyn ja mallinnustyökalujen kehityksessä, mihin viitataan usein termillä probabilistinen ohjelmointi. Probabilistinen ohjelmointi mahdollistaa monipuolisempien todennäköisyysmallien tuomisen suosittelujärjestelmiin