Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Physiological-based cord clamping in preterm infants using a new purpose-built resuscitation table: A feasibility study

textabstractObjective: Physiological-based cord clamping (PBCC) led to a more stable cardiovascular adaptation and better oxygenation in preterm lambs, but in preterm infants, this approach has been challenging. Our aim was to assess the feasibility of PBCC, including patterns of oxygen saturation (SpO2) and heart rate (HR) during stabilisation in preterm infants using a new purpose-built resuscitation table. Design: Observational study. Setting: Tertiary referral centre, Leiden University Medical Centre, The Netherlands. Patients: Infants born below 35 weeks' gestational age. Interventions: Infants were stabilised on a new purpose-built resuscitation table (Concord), provided with standard equipment needed for stabilisation. Cord clamping was performed when the infant was stable (HR >100 bpm, spontaneous breathing on continuous positive airway pressure with tidal volumes >4 mL/kg, SpO2 ≥25th percentile and fraction of inspired oxygen (FiO2) <0.4). Results: Thirty-seven preterm infants were included; mean (SD) gestational age of 30.9 (2.4) weeks, birth weight 1580 (519) g. PBCC was successful in 33 infants (89.2%) and resulted in median (IQR) cord clamping time of 4:23 (3:00-5:11) min after birth. There were no maternal or neonatal adverse events. In 26/37 infants, measurements were adequate for analysis. HR was 113 (81-143) and 144 (129-155) bpm at 1 min and 5 min after birth. SpO2 levels were 58%(49%-60%) and 91%(80%-96%)%), while median FiO2 given was 0.30 (0.30-0.31) and 0.31 (0.25-0.97), respectively. Conclusion: PBCC in preterm infants using the Concord is feasible. HR remained stable, and SpO2 quickly increased with low levels of oxygen supply. Trial registration number: NTR6095, results

PALVELUTUOTTEEN HINNOITTELUN KEHITTÄMINEN

Tämän opinnäytetyön aiheena on palvelutuotteen hinnoittelun kehittäminen. Tutkimuksen kohteena on Tili- ja isännöitsijätoimisto Ky. Tili- ja isännöitsijätoimisto Ky on Vaasassa toimiva tili- ja isännöintitoimisto, joka tarjoaa taloushallinto- ja isännöintipalveluita yrityksille. Tutkimuksen tavoitteena on kehittää Tili- ja isännöitsijätoimisto Ky:n isännöitsijän palvelutuotteiden hinnoittelua. Hinnoittelumenetelmäksi valittiin toimintoperusteinen hinnoittelu, jonka lähtökohtana on selvittää asiakaskohtaisia välillisiä kustannuksia. Kysymys oli suorite-kohtaisten kustannusten laskemisesta, eli toimintoperusteisesta prosessilaskennasta. Toimintoperusteinen prosessilaskenta tukee hinnoittelun päätöstä. Toiminto-analyysin jälkeen selvitettiin resurssien kohdistumista yrityksen eri toiminnoille. Aluksi selvitettiin yrityksen kustannusajuri, jonka perusteella kustannukset on kohdistettu eri toiminnoille. Seuraavaksi selvitettiin toimintoajurin avulla toimintoihin liittyvät yksikkökustannukset. Tuotteiden hinnoittelussa myyntihinnan on tarkoituksena sisältää kaikkien kustannusten lisäksi voittotavoite. Tutkimuksen teoriaosuuden keskeisiä asioita ovat toimintoperusteisen kustannuslaskennan, sekä hinnoittelun perusteiden esittely. Niiden avulla voidaan perustella hinnoittelupäätöstä tukeva toimintolaskenta. Opinnäytetyössä esitellään lisäksi kustannusperusteista hinnoittelua sekä isännöintiä ja tilitoimistoa yleisesti. Tutkimusmenetelmänä käytettiin kvalitatiivista eli laadullista tutkimusta. Tutkimuksen teoriaosuuteen käytettiin toimintolaskennan, taloushallinnon alan sekä hinnoittelun teoriaan liittyvää kirjallisuutta. Aineistonkeruussa havainnoitiin yrityksen tilinpäätöstä vuodelta 2016 ja yrityksen toimintaa liittyviä ohjelmia sekä tietokantoja. Lisäksi haastateltiin Tili- ja isännöitsijätoimisto Ky:n omistajaa ja työntekijöitä.This research was designed to develop the used pricing method for the case firm Tili- ja isännöitsijätoimisto Ky. The main area of this research focused on the main service products in property management. The case firm offers financial accounting and management services to house companies and other customer companies. Activity based costing was selected as the new pricing method in order to identify the customer-specific indirect costs. The aim of activity-based costing was to support pricing decisions for the case firm. In the implementation steps, activities must be identified first, and then the process continues with an activity analysis. Once the costs of activity and its drivers have been identified and its costs have been determined, then the costs of activity is allocated to the service product. In the allocation process, when the activity driver has been determined, the cost per unit can then be determined. Once the product cost per unit has been determined then the case firm considers the generated value of its service product, so the pricing of all the service product sales cover the fixed expenses with any remaining contribution margin providing profits. The theoretical study of this thesis introduced activity based costing and pricing to support activity based cost implementation and pricing decisions. In addition, it introduced cost based pricing and property management business and accounting firms in general. This research was implemented using the qualitative research method. The research material consists of related activity based costing, financial management, management accounting and pricing literature. The theoretical information was gathered from scientific research, academic books and some material was collect-ed from the Internet. The empirical data in this research was gathered by observing the case company’s financial statement from the year 2016 together with some business activities related programs and databases. In addition, was collected by interviewing the case company owner and the other employers of the company

Spirits, Ghosts, Atmospheres of Capital

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association (GWA) studies (N=10,768 from European ancestry enrolled in pregnancy/birth cohorts) and followed up three lead signals in six replication studies (combined N=19,089). Rs7980687 on chromosome 12q24 (P=8.1×10(−9)), and rs1042725 on chromosome 12q15 (P=2.8×10(−10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P=3.8×10(−7) for rs7980687, P=1.3×10(−7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P=3.9×10(−6)). SNPs correlated to the 17q21 signal show genome-wide association with adult intra cranial volume(2), Parkinson’s disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness