Flow-Rate Out Measurement from a Well During Drilling

Master's thesis in Petroleum engineeringAccurate measurements of flow rate out is crucial in order to prevent unnecessary harm to the environment, equipment or personnel. Harmful situations, such as inflows can potentially be detected earlier with a precise measuring tool. The conventional methods to measuring flow rate out are not flawless, therefore this thesis aims to contribute in the development of a new and innovative measuring method. This thesis will present technical background and theoretical studies that are relevant to the simulation and experimental part. The simulations investigate the challenges linked with measuring and analyzing flow rate out of a well. The challenges include the effects of fluid compressibility and transient time periods. The experimental part of the thesis describes a new type of flow sensor that is developed and tested. From the simulation studies, among others the results show that: • Compressibility effects increases with increasing flow rates • Effects from compressibility increases with increasing bit depth • A decreasing effect of compressibility is observed when the density increases • Compressibility effects increase with increasing OWR • A trend of increasing compressibility effects is observed for more viscous fluids, compared to less viscous fluids • Compressibility effect increases when drilling in open hole sections will lower diameters The second objective of the thesis was to investigate and verify the measuring principle of a new flow sensor that is developed at IRIS. The experiments were conducted with water as circulation fluid. The results show a trend that correspond with the expected result, but the measuring principle could not be verified, as the measurements were affected by an excessive amount of noise. Regardless, the testing showed various aspects where the new flow sensor could be improved in order to verify the measuring principle

Bedre nytteverdi av blodkultur ved sepsis

Tema/problemstilling: Vårt kvalitetsforbedringsprosjekt er rettet mot behandling av pasienter med sepsis ved en indremedisinsk avdeling. Målet er å øke nytteverdien av blodkultur for å redusere bredspektret antibiotikabehandling. Kunnskapsgrunnlag: Det er sammenheng mellom bruk av bredspektrede antibiotika og resistensutvikling. Deeskalering, endring av antibiotikabehandlingen til et mer smalspektret regime etter blodkultursvar, er en strategi for å redusere bruk av bredspektrede antibiotika. Deeskalering hos sepsispasienter der blodkultursvaret med resistensbestemmelse tillater det er trygg praksis og anbefales i nasjonale retningslinjer for antibiotikabehandling i sykehus. Tiltak/kvalitetsindikator: Samtaler med leger på Diakonhjemmet og Ullevål sykehus bekrefter at flere pasienter blir stående unødvendig på bredspektret antibiotikabehandling etter at man har blodkultursvar, og at det kan være potensial for å sette i gang forbedringstiltak. Vi innfører et tiltak som sikrer direkte kontakt mellom mikrobiolog og aktuell kliniker. Vi har valgt indikatorer for å vurdere i hvor stor grad tiltak gjennomføres og positive og negative effekter av tiltaket. Ledelse/organisering: Vi har brukt PUKK-sirkelen og Kotters åtte punkter som verktøy for å strukturere prosjektperioden. Slik kan vi sette fokus på de delene av prosjektet som trenger ekstra oppmerksomhet. Vi vil forankre prosjektet i ledelsen gjennom god informasjon og forankring i sykehusets strategiplan. For å oppnå varig endring i praksis, vil vi blant annet gjennomføre halvårlige målinger etter at prosjektperioden er avsluttet. Konklusjon: Tiltaket vi foreslår bygger på allerede gjeldende systemer og vil kreve lite opplæring og ressurser. Effekten er lett målbar. Kunnskapsgrunnlaget viser også at intervensjoner for formidling av dyrkningssvar ved sepsis kan redusere bruken av bredspektret antibiotika uten skadelige bieffekter. Med bakgrunn i dette vil vi anbefale at tiltaket gjennomføres

Limited association between infections, autoimmune disease and genetic risk and immune activation in severe mental disorders

Background Low-grade inflammation may be part of the underlying mechanism of schizophrenia and bipolar disorder. We investigated if genetic susceptibility, infections or autoimmunity could explain the immune activation. Methods Seven immune markers were selected based on indicated associations to severe mental disorders (IL-1Ra, sIL-2R, IL-18, sgp130, sTNFR-1, APRIL, ICAM-1) and measured in plasma of patients with schizophrenia (SCZ, N = 732) and bipolar spectrum disorders (BD, N = 460) and healthy controls (HC, N = 938). Information on rate of infections and autoimmune diseases were obtained from Norwegian national health registries for a twelve-year period. Polygenic risk scores (PRS) of SCZ and BD were calculated from genome-wide association studies. Analysis of covariance were used to test effects of infection rate, autoimmune disease and PRS on differences in immune markers between patients and HC. Results Infection rate differed between all groups (BD > HC > SCZ, all p < 0.001) whereas autoimmune disease was more frequent in BD compared to SCZ (p = 0.004) and HC (p = 0.003). sIL-2R was positively associated with autoimmune disease (p = 0.001) and negatively associated with PRS of SCZ (p = 0.006) across SCZ and HC; however, associations represented only small changes in the difference of sIL-2R levels between SCZ and HC. Conclusion There were few significant associations between rate of infections, autoimmune disease or PRS and altered immune markers in SCZ and BD, and the detected associations represented only small changes in the immune aberrations. The findings suggest that most of the low-grade inflammation in SCZ and BD is explained by other factors than the underlying PRS, autoimmunity and infection rates.publishedVersio

Catechol-O-Methyltransferase Val158Met Polymorphism Associates with Individual Differences in Sleep Physiologic Responses to Chronic Sleep Loss

Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis. allelic frequencies were higher in whites than African Americans.-related treatment responses and risk factors for symptom exacerbation

An examination of the language construct in NIMH's research domain criteria:Time for reconceptualization!

The National Institute of Mental Health’s Research Domain Criteria (RDoC) Initiative “calls for the development of new ways of classifying psychopathology based on dimensions of observable behavior.” As aresult of this ambitious initiative, language has been identifi d as an independent construct in the RDoC matrix. In this article, we frame language within an evolutionary and neuro- psychological context and discuss some of the limitations to the current measurements of language. Findings from genomics and the neuroimaging of performance during language tasks are dis- cussed in relation to serious mental illness and within the context of caveats regarding measuring language. Indeed, the data collec- tion and analysis methods employed to assay language have been both aided and constrained by the available technologies, methodologies, and conceptual defi Consequently, differ- ent fields of language research show inconsistent defi s of language that have become increasingly broad over time. Individ- ually, they have also shown significant improvements in conceptual resolution, aswell as inexperimental and analytic techniques. More recently, language research has embraced collaborations across disciplines, notably neuroscience, cognitive science, and computa- tional linguistics and has ultimately re-defi classical ideas of language. As we move forward, the new models of language with their remarkably multifaceted constructs force a re-examination of the NIMH RDoC conceptualization of language and thus the neuroscience and genetics underlying this concept

Genome-wide association analysis of Parkinson's disease and schizophrenia reveals shared genetic architecture and identifies novel risk loci

Background Parkinson’s disease (PD) and schizophrenia (SCZ) are heritable brain disorders that both involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in SCZ patients before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders. Methods We analyzed recent large genome-wide associations studies (GWAS) on SCZ (n=77,096) and PD (n=417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci. Results We observed genetic enrichment in PD conditional on associations with SCZ, and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified nine novel PD risk loci and one novel SCZ locus at conditional FDR<0.01. Further, we identified nine genomic loci jointly associated with PD and SCZ at conjunctional FDR<0.05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. 65 out of 67 genes mapped to the shared loci are expressed in the human brain and show cell-type specific expression profiles. Conclusions Altogether, the study increases the understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders

Synaptic Dysbindin-1 Reductions in Schizophrenia Occur in an Isoform-Specific Manner Indicating Their Subsynaptic Location

Background: An increasing number of studies report associations between variation in DTNBP1, a top candidate gene in schizophrenia, and both the clinical symptoms of the disorder and its cognitive deficits. DTNBP1 encodes dysbindin-1, reduced levels of which have been found in synaptic fields of schizophrenia cases. This study determined whether such synaptic reductions are isoform-specific. Methodology/Principal Findings: Using Western blotting of tissue fractions, we first determined the synaptic localization of the three major dysbindin-1 isoforms (A, B, and C). All three were concentrated in synaptosomes of multiple brain areas, including auditory association cortices in the posterior half of the superior temporal gyrus (pSTG) and the hippocampal formation (HF). Tests on the subsynaptic tissue fractions revealed that each isoform is predominantly, if not exclusively, associated with synaptic vesicles (dysbindin-1B) or with postsynaptic densities (dysbindin-1A and -1C). Using Western blotting on pSTG (n = 15) and HF (n = 15) synaptosomal fractions from schizophrenia cases and their matched controls, we discovered that synaptic dysbindin-1 is reduced in an isoform-specific manner in schizophrenia without changes in levels of synaptophysin or PSD-95. In pSTG, about 92% of the schizophrenia cases displayed synaptic dysbindin-1A reductions averaging 48% (p = 0.0007) without alterations in other dysbindin-1 isoforms. In the HF, by contrast, schizophrenia cases displayed normal levels of synaptic dysbindin-1A, but 67% showed synaptic reductions in dysbindin-1B averaging 33% (p = 0.0256), while 80% showed synaptic reductions in dysbindin-1C averaging 35% (p = 0.0171). Conclusions/Significance: Given the distinctive subsynaptic localization of dysbindin-1A, -1B, and -1C across brain regions, the observed pSTG reductions in dysbindin-1A are postsynaptic and may promote dendritic spine loss with consequent disruption of auditory information processing, while the noted HF reductions in dysbindin-1B and -1C are both presynaptic and postsynaptic and could promote deficits in spatial working memory

Table S8: Strabismic lateral rectus (LR) vs. strabismic medial rectus (MR) data

Recent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus muscles may explain the specific association of schizophrenia with exotropia but not esotropia. Samples from horizontal extraocular muscles were obtained during strabismus surgery and compared with age- and muscle type-matched normal muscles from organ donors. We used PCR arrays to identify differences in gene expression among 417 signaling molecules. We then focused on established schizophrenia-related growth factors, cytokines, and regulators of the extracellular matrix. Among 36 genes with significantly altered gene expression in dysfunctional horizontal rectus muscles, over one third were schizophrenia-related: CTGF, CXCR4, IL1B, IL10RA, MIF, MMP2, NPY1R, NRG1, NTRK2, SERPINA3, TIMP1, TIMP2, and TNF (adjusted p value ≤ 0.016667). By PCR array, expression of three of these genes was significantly different in medial rectus muscles, while eleven were significantly altered in lateral rectus muscles. Comparing baseline levels between muscle types, three schizophrenia-related genes (NPY1R, NTRK2, TIMP2) had lower levels of expression in medial rectus muscles. Despite the surprisingly large number of schizophrenia-related genes with altered gene expression levels in dysfunctional muscles, the lack of specificity for medial rectus muscles undermines a model of shared, region-specific gene expression abnormalities between exotropia and schizophrenia, but rather suggests consideration of the alternative model: that exotropia-induced aberrant early visual experiences may enable and/or contribute as a causative factor to the development of schizophrenia

Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability

Genome wide association studies (GWAS) have revolutionized the study of complex diseases and have uncovered common genetic variants associated with an increased risk for major psychiatric disorders. A recently published schizophrenia GWAS replicated earlier findings implicating common variants in Transcription factor 4 (TCF4) as susceptibility loci for schizophrenia. By contrast, loss of function TCF4 mutations, although rare, cause Pitt-Hopkins syndrome (PTHS); a disorder characterized by intellectual disability (ID), developmental delay and behavioral abnormalities. TCF4 mutations have also been described in individuals with ID and non-syndromic neurodevelopmental disorders. TCF4 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that regulate gene expression at E-box-containing promoters and enhancers. Accordingly, TCF4 has an important role during brain development and can interact with a wide array of transcriptional regulators including some proneural factors. TCF4 may, therefore, participate in the transcriptional networks that regulate the maintenance and differentiation of distinct cell types during brain development. Here, we review the role of TCF4 variants in the context of several distinct brain disorders associated with impaired cognition