Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Glutamine synthesis rate in the hyperammonaemic rat brain using simultaneous localized in vivo H-1 and N-15 MRS

Objectives: Glutamine synthetase is a critical step in the glutamate-glutamine cycle, the major mechanism of glutamate neurotransmission and is implicated in the mechanism of ammonia toxicity. 15N MRS is an alternative approach to 13C MRS in studying glutamate- glutamine metabolism. 15N MRS studies allow to measure an apparent glutamine synthesis rate (Vsyn) which reflects a combination of the glutamate- glutamine cycle activity (Vnt) and net glutamine accumulation. The net glutamine synthesis (Vsyn-Vnt) can be directly measured from 1H NMR. Therefore, the aim of this study was to perform in vivo localized 1H MRS interleaved with 15N MRS to directly measure the net glutamine synthesis rate and the apparent glutamine synthesis rate under 15N labeled ammonia infusion in the rat brain, respectively. Methods: 1H and 15N MRS data were acquired interleaved on a 9.4T system (Varian/Magnex Scientific) using 5 rats. 15NH4Cl solution was infused continuously into the femoral vein for up to 10 h (4.5 mmol/h/kg).1 The plasma ammonia concentration was increased to 0.95±0.08 mmol/L (Analox GM7 analyzer). 1H spectra were acquired and quantified as described previously.2 15N unlocalized and localized spectra were acquired using the sequence;3 and quantified using AMARES and an external reference method.4 The metabolic model used to analyze the total Gln and 5-15N labeled Gln time courses is shown on Figure 1A. Results: Glutamine concentration increased from 2.5±0.3 to 15±3.3 mmol/kg whereas the total glutamate concentrations remained unchanged (Figure 1B). The linear fit of the time-evolution of the total Gln from the 1H spectra gave the net synthesis flux (Vsyn-Vnt), which was 0.021± 0.006 mmol/min per g (Figure 1D). The 5-15N Gln peak (_271 ppm) was visible in the first and all subsequent scans, whereas the 2-15N Gln/Glu peak (_342 ppm) appeared after B1.5 h (Figure 1C). From the in vivo 5-15N Gln time course, Vsyn = 0.29±0.1 mmol/min per g and a plasma NH3 fractional enrichment of 71%±6% were calculated. Vnt was 0.26±0.1 mmol/min/g, obtained assuming a negligible Gln efflux.5 Vsyn and Vnt were within the range of 13C NMR measurements.6 Conclusion: The combination of 1H and 15N NMR allowed for the first time a direct and localized measurement of Vnt and apparent glutamine synthesis rate. Vnt is approximately one order of magnitude faster than the net glutamine accumulation.

Chronic subdural hematomas treated by burr hole trepanation and a subperiostal drainage system.

OBJECTIVE: Most symptomatic chronic subdural hematomas are treated by subdural drainage. However, a subperiostal (i.e., extracranial) passive closed-drainage system in combination with double burr hole trepanation is used at our institution. Therefore, we wanted to analyze our results and compare them with the alternate treatment strategies reported in the current literature. METHODS: In a retrospective single-center study, we analyzed the data of all patients undergoing double burr hole trepanation with a subperiostal passive closed-drainage system. Data analysis included general patient data, complications, postoperative seizure rate, and outcome. RESULTS: One hundred forty-seven patients underwent surgery for 183 symptomatic chronic subdural hematomas. The perioperative mortality rate was 3.4%. Hematoma persistence or recurrence occurred in 13.1% of the cases. The postoperative seizure rate was 6.6%, and the infection rate was 1.6%, including 3 cases of superficial wound infection and 1 case with deep infection. The reintervention rate was 9.3%, including trepanation in 8.2% of the patients and craniotomy in 1.1%. The overall complication rate was 10.9%. CONCLUSION: Double burr hole trepanation combined with a subperiostal passive closed-drainage system is a technically easy, highly effective, safe, and cost-efficient treatment strategy for symptomatic chronic subdural hematomas. The absence of a drain in direct contact with the hematoma capsule may moderate the risk of postoperative seizure and limit the secondary spread of infection to intracranial compartments.

Space Competition and Time Delays in Human Range Expansions. Application to the Neolithic Transition

Space competition effects are well-known in many microbiological and ecological systems. Here we analyze such an effectin human populations. The Neolithic transition (change from foraging to farming) was mainly the outcome of a demographic process that spread gradually throughout Europe from the Near East. In Northern Europe, archaeological data show a slowdown on the Neolithic rate of spread that can be related to a high indigenous (Mesolithic) population density hindering the advance as a result of the space competition between the two populations. We measure this slowdown from a database of 902 Early Neolithic sites and develop a time-delayed reaction-diffusion model with space competition between Neolithic and Mesolithic populations, to predict the observed speeds. The comparison of the predicted speed with the observations and with a previous non-delayed model show that both effects, the time delay effect due to the generation lag and the space competition between populations, are crucial in order to understand the observations

Impact of Left-Turn Phasing on Older and Younger Drivers at High-Speed Signalized Intersections, 2004

Several recent studies have demonstrated differences in safety between different types of left-turn phasing—protected, permitted, and protected/permitted phasing. The issue in question is whether older and younger drivers are more affected by a particular type of left-turn phasing at high-speed signalized intersections and whether they are more likely to contribute to a left-turn related crash under a specific type of left-turn phasing. This study evaluated the impact of different types of left-turn phasing on older and younger drivers at high-speed signalized intersections in Iowa. High-speed signalized intersections were of interest since oncoming speeds and appropriate gaps may be more difficult to judge for older drivers and those with less experience. A total of 101 intersections from various urban locations in Iowa with at least one intersecting roadway with a posted speed limit of 45 mph or higher were evaluated. Left-turn related crashes from 2001 to 2003 were evaluated. Left-turn crash rate and severity for young drivers (14- to 24-year-old), middle-age drivers (25- to 64-year-old), and older drivers (65 years and older) were calculated. Poisson regression was used to analyze left-turn crash rates by age group and type of phasing. Overall, left-turn crash rates indicated that protected phasing is much safer than protected/permitted and permitted phasing. Protected/permitted phasing had the highest left-turn crash rates overall.

Interest rates mapping

The present study deals with the analysis and mapping of Swiss franc interest rates. Interest rates depend on time and maturity, defining term structure of the interest rate curves (IRC). In the present study IRC are considered in a two-dimensional feature space - time and maturity. Exploratory data analysis includes a variety of tools widely used in econophysics and geostatistics. Geostatistical models and machine learning algorithms (multilayer perceptron and Support Vector Machines) were applied to produce interest rate maps. IR maps can be used for the visualisation and pattern perception purposes, to develop and to explore economical hypotheses, to produce dynamic asset-liability simulations and for financial risk assessments. The feasibility of an application of interest rates mapping approach for the IRC forecasting is considered as well. (C) 2008 Elsevier B.V. All rights reserved.

Iowa Comprehensive Heart Disease and Stroke Plan, 2010-2014, March 22, 2010

Heart disease is the number one cause of death for both men and women nationally as well as in the state of Iowa, while stroke is the third leading cause of death. These two diseases are often grouped together under the broader term ―cardiovascular disease‖ (CVD), which accounts for one-third of all deaths within the state. Ongoing efforts to increase prevention of, and improve care for, those who experience CVD have resulted in a decline in the number of deaths in Iowa caused by these conditions. In 1991, the death rate as a result of cardiovascular disease was 344.9 per 100,000 people; by 2006, that number had fallen to 239.9. Deaths as a result of stroke have also dropped, from 74.7 in 1991 to 57.4 in 2006.1 Although progress has been made; these illnesses are still major causes of death and serious disability for many Iowans. Despite the fact that some progress has been made through past efforts, current data show that the journey must continue to achieve the long, quality filled lives that Iowans deserve, free of chronic disease. Up to this point, there has been a lack of involvement by stakeholders against heart disease and stroke in Iowa. Causes of CVD are largely known and preventable, and more must be done to educate and spread this information throughout the state. This comprehensive statewide plan is a call to action to improve prevention, treatment, and management of heart disease and stroke in Iowa. Through the commitment and collaborative efforts of many, the Iowa Comprehensive Heart Disease and Stroke Plan 2010-2014 provides a guide to improve the health status of all Iowans. The people of Iowa have a long history of working together to do the right thing. We must rise to the challenge of lowering the incidence of heart disease and stroke through early and ongoing education that stresses prevention and healthy lifestyle choices, medical services that provide evidence-based, effective treatment and long term care management without disparity, and environmental policies that support the prevention of heart disease and stroke in our schools, work sites, and communities. This strategic plan is a guide to improving cardiovascular health in Iowa through 2014.

Pankkitoiminnan riskienhallinta ja riskienhallintaraportointi Puolassa

Tutkimuksessa tarkastellaan julkisesti noteerattujen pankkien riskienhallintaraportoinnin nykykäytäntöä Puolassa. Tutkimus jakaantuu kahteen osaan: Tutkimuksen ensimmäisessä osassa esitellään pankkitoimintaa, pankkitoiminnan riskejä ja riskienhallintaa. Pankkitoiminnan riskejä ovat luotto- ja markkinariskit, lisäksi puhutaan operatiivisista ja ympäristöriskeistä. Tutkimuksen toisessa osassa selvitetään ja kuvataan sitä, millaista on tutkimuksen kohdeyritysten riskienhallinta ja riskienhallintaraportointi, tutkimuksen tarkoituksena on myös verrata pankkien riskienhallintaraportointia keskenään. Tutkimuksen kohteena on 13 Varsovan pörssissä listattua pankkia. Tutkimusaineistona käytetään näiden pankkien vuoden 2005 vuosikertomuksia. Kysymyksessä on laadullinen tapaustutkimus, jolle on tyypillistä kuvaileva ja selittävä tutkimusote. Aineiston analyysimenetelmänä on käytetty pattern matchingiä, jonka avulla tutkitaan aineistosta löytyviä riskienhallintaraportoinnin osatekijöitä/indikaattoreita ja verrataan niitä oletettuihin malleihin. Tutkittujen riskienhallintaraporttien perusteella voidaan todeta, että pankkitoiminnan ydinriskeistä: luotto-, korko-, valuutta- ja likviditeettiriskeistä raportoidaan hyvin. Sen sijaan puutteita löytyy operatiivisten ja ympäristöriskien raportoinnista. Suurin osa pankeista raportoi operatiivisista riskeistä, mutta raportointi on pintapuolista ja analysointi puuttuu. Ympäristöriskeistä raportointi ei ole yleistä. Raportoinnin laajuus ja informatiivisuus vaihtelevat pankkien kesken: Suuret, kansainväliset pankkikonsernit raportoivat riskeistään laajasti ja informatiivisesti, kun taas pienemmillä, kansallisilla pankeilla raportointi jää usean pankin kohdalla suppeaksi. Syitä raportoinnin eroille on monia: Yksi syistä on IFRS-standardien vakiintumaton käyttö pienimmillä, kansallisilla pankeilla verrattuna kansainvälisiin pankkikonserneihin. Kansainvälisillä pankkikonserneilla on paremmat valmiudet raportoida riskienhallinnastaan verrattuna pienimpiin pankkeihin, jotka julkaisivat tilinpäätöksensä ensimmäistä kertaa IFRS-standardien mukaisesti vuonna 2005. Yhtenä selittävänä tekijänäraportoinnin eroille voidaan myös mainita omistuspohja: sijoittajainformaation merkitys on korostunut erityisesti organisaatioissa, joissa on laaja, kansainvälinen omistuspohja. Sen sijaan valtio-omisteisessa yrityksessä sijoittajainformaation merkitys on vähäisempi. Myös yrityskulttuuri vaikuttaa siihen, missä laajuudessa, ja mitä tietoa yritys antaa julkisuuteen. Pankit ovat myös tarkkoja maineestaan, mitä tietoa voidaan julkaista ja mitä vaikutuksia tiedon julkaisemisellaon yrityskuvaan. Sen sijaan pankin koolla ei välttämättä ole vaikutusta riskienhallintaraportoinnin laajuuteen ja informatiivisuuteen.

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Complex patterns of global spread in invasive insects: eco-evolutionary and management consequences

The advent of simple and affordable tools for molecular identification of novel insect invaders and assessment of population diversity has changed the face of invasion biology in recent years. The widespread application of these tools has brought with it an emerging understanding that patterns in biogeography, introduction history and subsequent movement and spread of many invasive alien insects are far more complex than previously thought. We reviewed the literature and found that for a number of invasive insects, there is strong and growing evidence that multiple introductions, complex global movement, and population admixture in the invaded range are commonplace. Additionally, historical paradigms related to species and strain identities and origins of common invaders are in many cases being challenged. This has major consequences for our understanding of basic biology and ecology of invasive insects and impacts quarantine, management and biocontrol programs. In addition, we found that founder effects rarely limit fitness in invasive insects and may benefit populations (by purging harmful alleles or increasing additive genetic variance). Also, while phenotypic plasticity appears important post-establishment, genetic diversity in invasive insects is often higher than expected and increases over time via multiple introductions. Further, connectivity among disjunct regions of global invasive ranges is generally far higher than expected and is often asymmetric, with some populations contributing disproportionately to global spread. We argue that the role of connectivity in driving the ecology and evolution of introduced species with multiple invasive ranges has been historically underestimated and that such species are often best understood in a global context.

Pk-yritysten rahoituspalveluiden kehittäminen Varkauden talousalueella

Tässä tutkimuksessa selvitettiin Varkauden talousalueen pk-yritysten rahoituspalveluiden kehitystarpeita. Kuvailevaa tutkimusta käyttämällä selvitettiin mitä ongelmakohtia yritykset näkevät rahaliikenteessään, miten rahoitusrakennetta suunnitellaan ja minkälaisia tuotteita yrityksillä on käytössään. Mittareina tutkimuksessa käytettiin mm. kasvutavoitetta, pääomarakennetta ja tuottovaatimusten muodostamista. Tavoitteena oli tutkia mitkä tekijät vaikuttavat sijoituspäätöksentekoon ja mitä tekijöitä arvostetaan pankista saadussa palvelussa. Tutkimukseen valittiin Varkauden talousalueen suurimmat ja parhaan luottoluokituksen omaavat yritykset. Aineisto kerättiin luomalla sähköinen kyselylomake, joka lähetettiin 48 yritykseen tammikuussa 2009. Tutkimustulosten mukaan yritykset näkivät suurimmat kehitystarpeet sähköisessä taloushallinnossa, eri investointirahoitusvaihtoehdoissa ja julkisten sekä yksityisten rahoittajien yhteistyössä. Parempaa rahoitusneuvontaa kaivattiin investointirahoitukseen ja yrityskauppoihin liittyen. Suurimmalla osalla yrityksistä oli selkeät kasvutavoitteet sekä suunniteltu pääomarakenne. Suurimpia puutteita havaittiin mm. korkosuojaus- ja kassanhallinnan ratkaisuissa. Varainhoidon tuotteista mielenkiintoisimpana nähtiin pääomaturvatut ja kiinteää tuottoa maksavat vaihtoehdot. Sijoituspäätöksiin vaikuttavat paljon pankin luotettavuus sekä toimihenkilön asiantuntemus. Vastaavasti sijoituspäätös voi jäädä tekemättä, mikäli tuote on liian monimutkainen tai prosessi vaatii paljon aikaa ja paneutumista. Pankin palveluissa arvostetaan niin ikään luotettavuutta, helppoa asiointia sekä henkilökohtaista palvelua. Vastaajien koulutustaustalla ei näytä valittujen mittareiden perusteella olevan vaikutusta rahoitusosaamiseen. Alueella rahoitusongelmia kohdanneista yrityksistä lähes kaikki olivat kasvuhakuisia.

Technical and economic indicators of the yellow passion fruit tree irrigated with underground water supply

The research aimed to quantify technical and economic indicators of yellow passion fruit tree irrigated with fractions of irrigation with underground source of water, to generate information that helps farmers in decision making on the implementation of investment in irrigated fruit growing (yellow passion fruit). For this purpose, we used the passion fruit crop irrigated with Microjet type irrigation system, with conducting system in simple espaliers. The treatments consisted of five hours of application of the depth of water required by the crop with irrigation frequency of two days. The results showed that the highest yield (16660kg ha-1) was obtained with the fractionation of irrigation twice a day (50% to 7h and 50% to 21h30), which provided an increase in productivity of 54%, demonstrating the financial viability and being highly profitable to the interest rate of 2% per year, with low sensitivity of financial risk to real interest rates above the prevailing market.

Recovery of biomass-derived valuable compounds using chromatographic and membrane separations

Utilization of biomass-based raw materials for the production of chemicals and materials is gaining an increasing interest. Due to the complex nature of biomass, a major challenge in its refining is the development of efficient fractionation and purification processes. Preparative chromatography and membrane filtration are selective, energy-efficient separation techniques which offer a great potential for biorefinery applications. Both of these techniques have been widely studied. On the other hand, only few process concepts that combine the two methods have been presented in the literature. The aim of this thesis was to find the possible synergetic effects provided by combining chromatographic and membrane separations, with a particular interest in biorefinery separation processes. Such knowledge could be used in the development of new, more efficient separation processes for isolating valuable compounds from complex feed solutions that are typical for the biorefinery environment. Separation techniques can be combined in various ways, from simple sequential coupling arrangements to fully-integrated hybrid processes. In this work, different types of combined separation processes as well as conventional chromatographic separation processes were studied for separating small molecules such as sugars and acids from biomass hydrolysates and spent pulping liquors. The combination of chromatographic and membrane separation was found capable of recovering high-purity products from complex solutions. For example, hydroxy acids of black liquor were successfully recovered using a novel multistep process based on ultrafiltration and size-exclusion chromatography. Unlike any other separation process earlier suggested for this challenging separation task, the new process concept does not require acidification pretreatment, and thus it could be more readily integrated into a pulp-mill biorefinery. In addition to the combined separation processes, steady-state recycling chromatography, which has earlier been studied for small-scale separations of high-value compounds only, was found a promising process alternative for biorefinery applications. In comparison to conventional batch chromatography, recycling chromatography provided higher product purity, increased the production rate and reduced the chemical consumption in the separation of monosaccharides from biomass hydrolysates. In addition, a significant further improvement in the process performance was obtained when a membrane filtration unit was integrated with recycling chromatography. In the light of the results of this work, separation processes based on combining membrane and chromatographic separations could be effectively applied for different biorefinery applications. The main challenge remains in the development of inexpensive separation materials which are resistant towards harsh process conditions and fouling.

Currency Carry Trades – Excess Returns and Performance Optimization of G10 Currency Carry Trade Strategies during the Euro Era

This study examines the excess returns provided by G10 currency carry trading during the Euro era. The currency carry trade has been a popular trade throughout the past decades offering excess returns to investors. The thesis aims to contribute to existing research on the topic by utilizing a new set of data for the Euro era as well as using the Euro as a basis for the study. The focus of the thesis is specifically on different carry trade strategies’ performance, risk and diversification benefits. The study finds proof of the failure of the uncovered interest rate parity theory through multiple regression analyses. Furthermore, the research finds evidence of significant diversification benefits in terms of Sharpe ratio and improved return distributions. The results suggest that currency carry trades have offered excess returns during 1999-2014 and that volatility plays an important role in carry trade returns. The risk, however, is diversifiable and therefore our results support previous quantitative research findings on the topic.

Heart rate variability in young adults - Reference values and associations with cardiometabolic risk factors and vascular properties. The Cardiovascular Risk in Young Finns Study.

Background: The function of the autonomic nervous system (ANS) can be evaluated with heart rate variability (HRV). Decreased HRV is associated with aging, the male sex, increased heart rate, and overall increased cardiometabolic risk. It has been hypothesized that early atherosclerotic vascular changes and ANS function are related. Aims: The aims were to assess reference values on HRV in young adults, and examine associations with HRV and cardiometabolic risk factors and metabolic syndrome (MetS) and to study relations between HRV and ultrasonographically measured vascular properties. Participants and methods: The present thesis is part of the Cardiovascular Risk in Young Finns Study. The thesis is based on the follow-up study in 2001, when the study individuals were 24-39 years of age. HRV data were available on 1 956 individuals. Results: HRV was inversely associated with age and heart rate (for all p<0.001). Highfrequency HRV (HF) was higher, and low-frequency HRV (LF) lower in women than men (p<0.0001 for both). MetS was associated with 11% decreased HF and 12% increased LF/HF-ratio in women, and 8% decreased HF and 4% increased LF/HF-ratio in men. Carotid artery distensibility was independently associated with HF and total HRV (for both p<0.05). Conclusions: The reference values in young adults were generated. Decreased HRV was associated with age, the male sex and increased heart rate. Women had higher HF and lower LF variability than men. MetS was related to decrease in HRV. The observed associations between carotid elasticity and HRV, supports the hypothesis that reduction in carotid elasticity may lead to decrease in autonomic cardiac control.