Economic Inequality and Health: Looking Beyond Aggregate Indicators

This paper examines the relationship between relative income inequality and health in Finland, using individual microdata over the period 1993-2005. Our data allows us to analyse a large spectrum of health indicators. Overall, our results suggest that income inequality is not associated with increased morbidity in the population. The results for women differ to quite a large extent from those of men and the pooled sample. There is evidence that an increase in the Gini coefficient is negatively related to the probability of good physical health and no disability retirement. For men, relative income inequality is clearly not important for health.Health, health behaviour, economic inequality, relative income inequality, relative deprivation, Gini coefficient

Q-funktion minimax-approksimointi eksponenttisummalla

Langaton tiedonsiirto on läsnä kaikkialla yhteiskunnassa. Siirrettyjen datamäärien kasvaessa tiedonsiirron laadukkuus on erityisen tärkeää. Tietoliikennetekniikassa tiedonsiirron virheettömyyttä voidaan arvioida tilastollisin keinoin käyttäen normaalijakauman eli Gaussin jakauman häntäfunktiota, Q-funktiota. Q-funktiota hyödynnetään tiedonsiirron symboli- ja bittivirhetodennäköisyyksien laskemisessa siten, että sen parametrinaan saama signaali-kohinasuhde SNR saa eri kertoimia käytetystä digitaalisesta modulaatiosta ja modulaation konstellaatiosta riippuen. Signaali-kohinasuhteen kasvaessa tiedonsiirron virhetodennäköisyys pienenee, ja käytännön suunnittelutyö onkin tasapainon hakemista riittävän signaali-kohinasuhteen ja kyllin pienen tiedonsiirron virhetodennäköisyyden saavuttamiseksi. Käyttökelpoisuudestaan huolimatta Q-funktio on matemaattisesti hankala integraalifunktio, jonka saamat arvot voidaan ratkaista vain numeerisesti laskentaohjelmalla. Analyyttistä käsittelyä varten Q-funktiosta onkin kehitetty useisiin eri lähestymistapoihin perustuvia approksimaatioita, joiden avulla Q-funktion saamia arvoja voidaan ratkaista riittävällä tarkkuudella. Tutkielmassa esitellään tietoliikennetekniikassa merkityksellisimmät lähestymistavat: rajoihin perustuvat approksimaatiot, eksponenttifunktioon perustuvat approksimaatiot, polynomieksponenttifunktioon perustuvat approksimaatiot ja eri funktioihin perustuvat approksimaatiot. Varsinainen tutkimuskysymys on erään tietyn eksponenttifunktioon perustuvan minimax-approksimaation jatkokehitys. Kyseisessä approksimaatiossa eksponenttifunktion kertoimet saadaan minimoimalla approksimaation absoluuttisen ja suhteellisen virheen tuottamaa kokonaisvirhettä siten, että virheitä kuvaavat epälineaariset yhtälöryhmät ratkaistaan Newtonin menetelmällä numeerisesti. Tässä tutkielmassa absoluuttisen virheen ratkaisemiseen esitetään analyyttisesti ratkaistu Jacobin matriisi, jonka avulla vältetään numeerisen laskennan tarpeetonta raskautta menetelmää käytettäessä. Analyyttisesti ratkaistu Jacobin matriisi voidaan myöhemmin toteuttaa laskentaohjelmaan sopivana kooditoteutuksena, jolla approksimaation vaatimaa prosessointitehoa ja -aikaa voidaan pienentää ja Newtonin menetelmän vaatiman alkuarvauksen saamista mahdollisesti helpottaa. Tutkielman lopussa esitetään jatkokehitysideoita tulevaa tutkimusta varten

Does a Slump Really Make You Thinner? Finnish Micro-level Evidence 1978-2002

This paper explores the relationship between obesity and economic conditions in Finland, using individual microdata from 1978 to 2002. The results reveal that an improvement in regional economic conditions measured by the employment-to-population ratio produces a decrease in obesity over the period of investigation, other things being equal. This effect arises from the decline in the height-adjusted weight of people who are deeply overweight, (BMI>35). In addition, the effect is strongest for the people in later middle age (aged 45-65). The incidence of obesity is unrelated to the regional growth rate. All in all, the Finnish evidence presented does not support the conclusions reported for the USA, according to which temporary economic slowdowns are good for health. In contrast, at least overweight increases during slumps.overweight, business cycles, health

HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression

The HLA gene complex is the most important single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. Most studies have focused on the vast allelic variation in these genes; only a few studies have explored differences in the expression levels of HLA alleles. In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology. Our method provides novel insights into HLA research, and it can be applied to quantify expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.Peer reviewe

Economic Inequality and Health: Looking Beyond Aggregate Indicators

This paper examines the relationship between relative income inequality and health in Finland, using individual microdata over the period 1993-2005. Our data allows us to analyse a large spectrum of health indicators. Overall, our results suggest that income inequality is not associated with increased morbidity in the population. The results for women differ to quite a large extent from those of men and the pooled sample. There is evidence that an increase in the Gini coefficient is negatively related to the probability of good physical health and no disability retirement. For men, relative income inequality is clearly not important for health

Economic Inequality and Health: Looking Beyond Aggregate Indicators

This paper examines the relationship between relative income inequality and health in Finland, using individual microdata over the period 1993-2005. Our data allows us to analyse a large spectrum of health indicators. Overall, our results suggest that income inequality is not associated with increased morbidity in the population. The results for women differ to quite a large extent from those of men and the pooled sample. There is evidence that an increase in the Gini coefficient is negatively related to the probability of good physical health and no disability retirement. For men, relative income inequality is clearly not important for health

Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34 (+)CD38(-) stem and progenitor cells in chronic myeloid leukemia

Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC. Based on these results, the 5-LO inhibitor zileuton has been introduced in clinical trials as a therapeutic option to target the LSC although its effect on primary human CML LSC has not been studied. We have here by using multiplex single cell PCR analyzed the expression of the mediators of the leukotriene pathway in bone marrow (BM) BCR-ABL(+)CD34(+)CD38(-) cells at diagnosis, and found low or undetectable expression of ALOX5. In line with this, zileuton did not exert significant overall growth inhibition in the long-term culture-initiating cell (LTC-IC) and colony (CFU-C) assays of BM CD34(+)CD38(-) cells from 7 CML patients. The majority of the single leukemic BCR-ABL(+)CD34(+)CD38(-) cells expressed cysteinyl leukotriene receptors CYSLTI and CYSLT2. However, montelukast, an inhibitor of CYSLTI, also failed to significantly suppress CFU-C and LTC-IC growth. These findings indicate that targeting ALOX5 or CYSLTI signaling with leukotriene antagonists, introduced into the clinical practice primarily as prophylaxis and treatment for asthma, may not be a promising pharmacological strategy to eradicate persisting LSC in CML patients. (C) 2017 The Author(s). Published by Elsevier Inc.Peer reviewe

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted—via a primary-data based pipeline—a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a ‘secondary’ hallmark of T-PLL

Neuronavigated Versus Non-navigated Repetitive Transcranial Magnetic Stimulation for Chronic Tinnitus: A Randomized Study

Repetitive transcranial magnetic stimulation (rTMS) has shown variable effect on tinnitus. A prospective, randomized 6-month follow-up study on parallel groups was conducted to compare the effects of neuronavigated rTMS to non-navigated rTMS in chronic tinnitus. Forty patients (20 men, 20 women), mean age of 52.9 years (standard deviation [SD] = 11.7), with a mean tinnitus duration of 5.8 years (SD = 3.2) and a mean tinnitus intensity of 62.2/100 (SD = 12.8) on Visual Analog Scale (VAS 0–100) participated. Patients received 10 sessions of 1-Hz rTMS to the left temporal area overlying auditory cortex with or without neuronavigation. The main outcome measures were VAS scores for tinnitus intensity, annoyance, and distress, and Tinnitus Handicap Inventory (THI) immediately and at 1, 3, and 6 months after treatment. The mean tinnitus intensity (hierarchical linear mixed model: F3 = 7.34, p = .0006), annoyance (F3 = 4.45, p = .0093), distress (F3 = 5.04, p = .0051), and THI scores (F4 = 17.30, p F3 = 2.96, p = .0451) favoring the non-navigated rTMS. Reduction in THI scores persisted for up to 6 months in both groups. Cohen’s d for tinnitus intensity ranged between 0.33 and 0.47 in navigated rTMS and between 0.55 and 1.07 in non-navigated rTMS. The responder rates for VAS or THI ranged between 35% and 85% with no differences between groups (p = .054–1.0). In conclusion, rTMS was effective for chronic tinnitus, but the method of coil localization was not a critical factor for the treatment outcome.</p

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted-via a primary-data based pipeline-a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a 'secondary' hallmark of T-PLL