Predikstolen som försvann - en studie av predikoplatsen hos Rolf Bergh, Sigurd Lewerentz, Ove Hidemark och Jerk Alton i den liturgiska förnyelsens kölvatten

The purpose of this thesis is to illustrate theological and architectural currents, which have directly come to influence the pulpit in churches built since the 1950s. I have limited my presentation to include Swedish churches only. More specifically, I describe four prominent architects, and their design and placement of the pulpit. These are Rolf Bergh, Sigurd Lewerentz, Ove Hidemark and Jerk Alton. In my thesis, I have found that the liturgical renewal during the second half of the 20th century in many ways has come to constitute the liturgical thoughts behind new church buildings in Sweden. I have also found, that the pulpit in general since the 1950s has declined in importance. Although the liturgical movement initially gave it an altered but still important role, I can state that the pulpit in newly built churches in most cases is replaced by a simple ambo. This is problematic, as the preached word historically has played a very significant role in the Swedish Lutheran Church. I have also found, that the studied architects have wanted to stand outside the contemporary architectural trends, in search of more persistent values. Also, I have found a clear connection between the pulpit or ambo, and the architect and his or hers personal conception of theology and liturgy

A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements

Background: High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e. g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a preprocessing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns. Results: We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background. Conclusions: The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise

Спинальная анестезия при оперативном родоразрешении беременных с гестозом

БЕРЕМЕННОСТИ ОСЛОЖНЕНИЯПРЕЭКЛАМПСИЯРОДОВСПОМОЖЕНИЕАКУШЕРСКИЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИИАНЕСТЕЗИЯ СПИННОМОЗГОВАЯРОДОРАЗРЕШЕНИЯ ПРОЦЕС

Phenotype standardization for statin-induced myotoxicity

Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.</p

Токсикологическая безопасность спиртосодержащих лекарственных средств для профилактической антисептики

ЛЕКАРСТВА СОЗДАНИЕЛЕКАРСТВА КОНСТРУИРОВАНИЕЛЕКАРСТВА МОДЕЛИРОВАНИЕПРОТИВОИНФЕКЦИОННЫЕ СРЕДСТВА ЛОКАЛЬНЫЕ /АНАЛ /ТОКСИЧАНТИСЕПТИКИ /АНАЛ /ТОКСИЧАНТИСЕПТИЧЕСКИЕ СРЕДСТВА /АНАЛ /ТОКСИЧПРОТИВОИНФЕКЦИОННЫЕ СРЕДСТВА МЕСТНЫЕ /АНАЛ /ТОКСИЧЛЕКАРСТВ ТОКСИЧНОСТЬЭТАНОЛ /ТОКСИЧСПИРТ ЭТИЛОВЫЙ /ТОКСИЧЛЕКАРСТВ ФИЗИОЛОГИЧЕСКОЕ ДЕЙСТВИЕИОДХЛОРГЕКСИДИНЭКСПЕРИМЕНТЫ НА ЖИВОТНЫХКРЫСЫЦелью работы было изучение показателей токсикологической безопасности разработанных спиртосодержащих лекарственных средств "Витасепт" для профилактической антисептики. Выполнено 4 серии опытов на половозрелых белых крысах мужского пола массой 250±25 г, содержащихся в стандартных условиях. Однократное внутрижелудочное введение крысам нативных антисептических средств, содержащих спирт этиловый 72% марки "Люкс" с бриллиантовым зеленым 0,001%, с йодом кристаллическим 0,25%, с хлоргексидина биглюконатом 0,1%, а также "Этанол, раствор для наружного применения, 70%" в дозе 5300 мг/кг массы тела крыс, не вызывает гибель подопытных животных. После однократной 4-часовой аппликации в дозе 20 мг/см{2} закрытым способом и десятикратных повторных аппликаций на выстриженный участок кожи, а также хвосты крыс через 1,16 ч и в последующие 12 суток наблюдения после аппликации не вызывают гибель подопытных животных, клинические симптомы интоксикации и раздражение кожи. Все исследуемые средства имели специфический спиртовой запах, были прозрачными, подлинными, с плотностью 0,877 до 0,885 г/см{3}. Полученные результаты позволяют заключить, что исследованные инновационные лекарственные антисептические средства, содержащие экологически чистый спирт этиловый марки "Люкс" 72% с бриллиантовым зеленым 0,001%, с йодом кристаллическим 0,25%, с хлоргексидина биглюконатом 0,5% и 0,1%, а также оригинальные лекарственные антисептические средства, содержащие экологически чистый спирт этиловый марки "Люкс" 72% с бриллиантовым зеленым 0,01%, с йодом кристаллическим 0,5%, являются малоопасными, практически безвредными и не обладают кожно-раздражающим действием. Разработанные нами в настоящее время спиртосодержащие антисептики, а также производимые ОАО "Бобруйский завод биотехнологий" средства под маркой "Витасепт-СКЗ", "Витасепт-СКИ" и "Витасепт-СКО" соответствуют нормативным требованиям по токсикологическим показателям безопасности, предъявляемым к кожным антисептикам, средствам для гигиенической и хирургической обработки рук, кожи операционного и инъекционного полей.The aim of this work was to study the toxicological safety indicators of the developed alcohol-containing medicinal agents "Vitasept" for prophylactic antisepsis. 4 series of experiments were performed on adult white male rats weighing 250±25 g kept in standard conditions. A single intragastric administration to rats of native antiseptics containing 72% ethanol of the brand de luxe with diamond green 0.001%, with crystalline iodine 0.25%, with chlorhexidine bigluconate 0.1%, as well as "Ethanol, solution for external use, 70%" at a dose of 5300 mg/kg of rat body weight does not cause the death of experimental animals. After a single 4-hour application at a dose of 20 mg/cm{2} in a closed manner and ten times repeated applications on a sheared skin area, as well as rat tails after 1,16 hours and in the next 12 days of observation after application, they do not cause the death of experimental animals, clinical symptoms of intoxication and skin irritation. All studied agents had a specific alcoholic smell, were transparent, genuine, with a density of 0.877 up to 0.885 g/cm{3}. The results obtained allow us to conclude that the studied innovative medicinal antiseptic agents containing environmentally friendly 72% ethanol of the brand de luxe with brilliant green 0.001%, with crystalline iodine 0.25%, with chlorhexidine bigluconate 0.5% and 0.1%, as well as original medicinal antiseptic agents containing environmentally friendly 72% ethanol of the brand de luxe with brilliant green 0.01%, with crystalline iodine 0.5%, are slightly hazardous, practically harmless and do not produce a skin-irritating effect. Currently developed alcohol-containing antiseptics, as well as products manufactured by "Bobruisk plant of biotechnologies" under the brand names "Vitasept-SKZ", "Vitasept-SKI" and "Vitasept-SKO", comply with the regulatory requirements for toxicological safety indicators of skin antiseptics, agents for hygienic and surgical treatment of hands, skin of the operative and injection fields

A multi-factorial analysis of response to warfarin in a UK prospective cohort

Background Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin. Methods A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R. Results VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role. Conclusion Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both VKORC1 and CYP2C9*3 are important determinants of the initial INR response to warfarin. Other novel variants, which did not reach genome-wide significance, were identified for the different outcome measures, but need replication

Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians

Objectives: To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction. Methods: Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1-1639 G.A, CYP4F2 1347 G.A, CYP2C9*2,*3 and GGCX 12970 C.G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and also with the clinical data for various performance measures. Odds ratios for association of genotypes with drug sensitive and resistant groups were calculated. Results: The pharmacogenetic dosing algorithm generated by multiple regression analysis explains 41.4 % (p-value,0.001) of dosage variation. Validation of the new algorithm showed its predictive ability to be better than the already established algorithms based on similar variables. Its validity in our population is reflected by increased sensitivity, specificity, accuracy and decreased rates of over- and under- estimation in comparison to clinical data. The VKORC1-1639 G.A polymorphism was found to be strongly associated with acenocoumarol sensitivity according to recessive model. Conclusions: We have proposed an efficient north India specific pharmacogenetic acenocoumarol dosing algorithm whic

Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment

Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10−5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10−8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05–2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema

Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians

<p>Abstract</p> <p>Background</p> <p><it>CYP2C9 </it>and <it>VKORC1 </it>are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs) in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients.</p> <p>Methods</p> <p>Direct sequencing method was used to identify SNPs in <it>CYP2C9, VKORC1, CYP4F2, EPHX1, PROC </it>and <it>GGCX </it>genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.</p> <p>Results</p> <p>From the 40 SNPs analyzed, <it>CYP2C9 </it>rs17847036 and <it>VKORC1 </it>rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between <it>CYP2C9*3, CYP2C9C</it>-65 (rs9332127), <it>CYP4F2 </it>rs2108622, <it>GGCX </it>rs12714145, <it>EPHX1 </it>rs4653436 and <it>PROC </it>rs1799809 with warfarin sensitivity.</p> <p>Conclusions</p> <p><it>VKORC1 </it>rs9923231 AA and <it>CYP2C9 </it>rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively). <it>CYP2C9 </it>and <it>VKORC1 </it>genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.</p