Weera 2.0 - Supplementary construction plan for the central block of Lappeenranta

Lappeenrannan ydinkeskustan niin kutsutussa Weeran korttelissa puhaltavat muutoksen tuulet. Kortteliin on tehty asemakaavamuutos vuonna 2021, minkä myötä korttelista on samana vuonna purettu kaksi rakennusta – kauppakeskus Weera ja hotelli Scandic. Asemakaavamuutoksen yhteydessä korttelista myös suojeltiin kaksi rakennusta: liikekeskus Karjalankulma ja vanha SYP:n pankkirakennus laajennuksineen. Vielä vuoden 2023 kevääseen mennessä kortteliin tulevista rakennuksista ei ole julkisesti esitelty minkäänlaista materiaalia. Tyhjä tontti keskellä Lappeenrannan ydinkeskustaa innoitti tutkimaan korttelin mahdollisuuksia ja lopputuloksena syntyi tämä itsenäisenä tutkielmana tehty diplomityö. Tässä diplomityössä suunnitellaan täydennysrakentamista Weeran kortteliin. Työn tavoitteena on täydentää Weeran kortteli eheäksi kokonaisuudeksi, joka liittyy luontevasti osaksi ympäröivää kaupunkirakennetta. Uusien rakennusten massoittelulla ja arkkitehtuurilla halutaan sopeutua korttelin suojeltuihin rakennuksiin. Tavoitteena on suunnitella kestävän kehityksen mukaisia rakennuksia, joiden sekoittuneet toiminnot tukevat toisiaan ja mahdollistavat vilkkaan kaupunkielämän korttelin alueella. Suunnittelupainotteista diplomityötä tukee historiakatsaus Lappeenrannan kaupungin ja Weeran korttelin rakentumisesta. Katsauksessa perehdytään Lappeenrannan ja Weeran korttelin rakentumisen vaiheisiin sekä nykyiseen kaupunkikuvaan. Suunnittelutyön pohjaksi tutkitaan myös Lappeenrannan kaupungin tavoitteita ja strategiaa ilmastotietoisena edelläkävijäkaupunkina. Työn suunnitteluosuus koostuu korttelin ja ympäröivän kaupunkirakenteen analyyseista, luonnoksista sekä lopputuloksena syntyneestä täydennysrakentamissuunnitelmasta. Työn tärkeäksi tutkimuskysymykseksi muodostui miten täydennysrakentamisella voidaan luontevasti eheyttää rikkonaista korttelirakennetta sekä samalla kohottaa yleistä kaupunkikuvaa ja Lappeenrannan imagoa. Lopputuloksena syntynyt suunnitelma osoittaa, että kohteen historiaan ja kaupungin tavoitteisiin perehtymällä voi saada aikaan onnistuneita kokonaisuuksia, joiden perustellut toiminnot ja ympäristöstä ammentava arkkitehtuuri parantavat osaltaan ydinkeskustan aluetta.Big changes are to be made in the so-called “Weera’’ block, a central part of Lappeenranta. The block has undergone an alteration of a city plan in 2021. As a result, two buildings have been demolished from the block – the Weera shopping center and the Scandic hotel. In connection with the new city plan, two buildings on the block were also protected: business center Karjalankulma and the old SYP bank building, including their extensions. Until the spring of 2023, no official plans have been presented about the new buildings coming to the block. An empty lot in the middle of Lappeenranta’s core inspired me to explore the possibilities of the block. The end result was this master’s thesis, which was done independently, out of my own interest. In this master’s thesis, a supplementary construction is planned for the Weera block. The goal of the thesis is to complete the Weera block into a complete entity, making the block a natural part of the surrounding urban structure. The massing and architecture of the new buildings were designed to adapt to the block’s protected buildings. The goal was to design buildings in line with sustainable development, whose mixed functions support each other and enable lively urban life in the area of the block. The design-oriented master’s thesis is supported by a historical overview of the construction of the city of Lappeenranta and the Weera block. In the overview, the stages of the construction of the Lappeenranta and Weera blocks are reviewed, as well as the current cityscape. The goals and strategy of the city of Lappeenranta as a climate-conscious pioneer city are also explored as part of the research. The design part of the thesis consists of analyzes, sketches and the resulting supplementary construction plan. The important research question of the thesis was how to use supplementary construction to naturally integrate the broken block structure while also raising the image of Lappeenranta. The resulting plan shows that by getting familiar with the history of the site and the city’s goals, you can create successful entities whose well-reasoned functions and architecture drawing from the environment contribute to the improvement of the city centre

Eteisvärinää sairastavien potilaiden antikoagulaatiohoito ja palveluiden käyttö Suomessa

Vertaisarvioitu. English summary.Lähtökohdat : Suoria antikoagulantteja ja varfariinia käytetään ei-läppäperäiseen eteisvärinään liittyvän aivohalvauksen estossa, mutta toistaiseksi eri antikoagulaatiolääkityksellä olevista suomalaisista potilaista on rajallisesti tosielämän tietoon perustuvia tutkimuksia. Menetelmät : utkimme rekisteritiedolla antikoagulaatiohoitoa saavien eteisvärinäpotilaiden palvelukäyttöä, lääkitystä sekä potilasprofiilia. Tarkastelimme lääkesegmenteittäin sosiaali- ja terveyspalvelujen käyttöä ja kustannuksia sekä aivotapahtumista ja ruoansulatuskanavan vuodoista johtuvia erikoissairaanhoidon ja ¬perusterveydenhuollon käyntejä ja hoitopäiviä potilailla, jotka olivat käyttäneet vähintään vuoden ¬samaa antikoagulanttia. Tulokset : Varfariinia ja apiksabaania määrätään keskimäärin vanhemmille ja korkeamman riskin potilaille kuin muita antikoagulantteja. Eteisvärinäpotilaiden yhteenlasketut sote-palveluiden kustannukset olivat vuonna 2018 noin 2 miljardia euroa. Haittatapahtumista aivoinfarktit ja aivotapahtumien jälkitilat aiheuttivat eteisvärinä¬potilaille eniten palvelukäyttöä. Päätelmät : Eteisvärinäpotilaiden hoidosta kertyy yhteiskunnalle suuria kustannuksia. Suoria antikoagulantteja ja varfariinia käyttävien potilaiden välillä on eroja potilasprofiilissa sekä palvelukäytössä ja sen kustannuksissa.Peer reviewe

Eteisvärinää sairastavien potilaiden antikoagulaatiohoito ja palveluiden käyttö Suomessa

Lähtökohdat Suoria antikoagulantteja ja varfariinia käytetään ei-läppäperäiseen eteisvärinään liittyvän aivohalvauksen estossa, mutta toistaiseksi eri antikoagulaatiolääkityksellä olevista suomalaisista potilaista on rajallisesti tosielämän tietoon perustuvia tutkimuksia. Menetelmät Tutkimme rekisteritiedolla antikoagulaatiohoitoa saavien eteisvärinäpotilaiden palvelukäyttöä, lääkitystä sekä potilasprofiilia. Tarkastelimme lääkesegmenteittäin sosiaali- ja terveyspalvelujen käyttöä ja kustannuksia sekä aivotapahtumista ja ruoansulatuskanavan vuodoista johtuvia erikoissairaanhoidon ja ­perusterveydenhuollon käyntejä ja hoitopäiviä potilailla, jotka olivat käyttäneet vähintään vuoden ­samaa antikoagulanttia. Tulokset Varfariinia ja apiksabaania määrätään keskimäärin vanhemmille ja korkeamman riskin potilaille kuin muita antikoagulantteja. Eteisvärinäpotilaiden yhteenlasketut sote-palveluiden kustannukset olivat vuonna 2018 noin 2 miljardia euroa. Haittatapahtumista aivoinfarktit ja aivotapahtumien jälkitilat aiheuttivat eteisvärinä­potilaille eniten palvelukäyttöä. Päätelmät Eteisvärinäpotilaiden hoidosta kertyy yhteiskunnalle suuria kustannuksia. Suoria antikoagulantteja ja varfariinia käyttävien potilaiden välillä on eroja potilasprofiilissa sekä palvelukäytössä ja sen kustannuksissa.</p

Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies

There is limited evidence for any dietary factor, except alcohol, in breast cancer (BC) risk. Therefore, studies on a whole diet, using diet quality indices, can broaden our insight. We examined associations of the Nordic Diet (mNDI), Mediterranean diet (mMEDI) and Alternative Healthy Eating Index (mAHEI) with postmenopausal BC risk. Five Finnish cohorts were combined including 6374 postmenopausal women with dietary information. In all, 8-9 dietary components were aggregated in each index, higher total score indicating higher adherence to a healthy diet. Cox proportional hazards regression was used to estimate the combined hazard ratio (HR) and 95% confidence interval (CI) for BC risk. During an average 10-year follow-up period, 274 incident postmenopausal BC cases were diagnosed. In multivariable models, the HR for highest vs. lowest quintile of index was 0.67 (95 %CI 0.48-1.01) for mNDI, 0.88 (0.59-1.30) for mMEDI and 0.89 (0.60-1.32) for mAHEI. In this combined dataset, a borderline preventive finding of high adherence to mNDI on postmenopausal BC risk was found. Of the indices, mNDI was more based on the local food culture than the others. Although a healthy diet has beneficially been related to several chronic diseases, the link with the etiology of postmenopausal BC does not seem to be that obvious.Peer reviewe

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis