Miten tyhjä kirjoitetaan?:havaintoja tyhjyydestä Virginia Woolfin teoksessa To the Lighthouse

Tiivistelmä. Tarkastelen tutkielmassani tyhjyyttä Virginia Woolfin teoksessa To the Lighthouse (1927). Pohdin, miten Woolf kirjoittaa tyhjän kohdeteoksessani ja minkälaisia merkityksiä hän antaa tyhjyydelle. Teen havaintoja tyhjyydestä sekä kartoittamalla kohdeteokseni tyhjyyteen liittyvää sanastoa että tarkastelemalla muuten niitä keinoja, joilla Woolf pyrkii tyhjyyttä ilmaisemaan. Tutkielmani johdannossa tuon esille sitä, miten tyhjyyttä voi tarkastella eri näkökulmista. Esittelen siinä myös eri ajattelijoiden fiktiivisen maailman tiloihin ja erityisesti taloon liittyviä ajatuksia. Käsittelen tutkielmani toisessa pääluvussa kohdeteokseni sanastoa. Tyhjyys ilmaistaan To the Lighthouse -teoksessa useimmiten sanoilla empty, emptiness ja nothingness. Woolfille tyhjyys on teoksessa useammin konkreettista kuin abstraktia, mutta tämä konkreettinen tyhjyys saa usein abstrakteja merkityksiä. Hän siis hyödyntää konkreettista tyhjyyttä kerronnallisen aukon kaltaisesti. Sanastoa tutkiessani minulle syntyy se vaikutelma, että Woolf hyödyntää tyhjyyttä tietoisesti. Woolf ilmaisee tyhjyyttä myös muutoksella fokalisoinnissa teoksen keskimmäisen osan alussa. Hän käyttää myös erilaisia runouden keinoja kertoessaan tyhjyydestä. Konkreettiset tyhjät tilat liittyvät kohdeteoksessani kuolemaan ja erityisesti poissaoloon. Käsittelen näitä aiheita kolmannessa pääluvussa. Poissaolossa on mukana aimo annos läsnäoloa, mistä syntyy se vaikutelma, ettei Woolf oikeastaan tyydy tyhjyyteen. Tutkielmassani neljännessä pääluvussa tarkastelen teoksen kolmen päähenkilön tyhjyyteen liittyviä kokemuksia ja tunteita. Silmiinpistävintä tyhjyyttä teoksessa on sen keskimmäisen osan runollinen kuvaus tyhjästä talosta. Mr. Ramsay pelkää tyhjyyttä; hän uskoo tuhoutuvansa, jos hänen talonsa tyhjenee elämästä. Pimeässä seikkailevan Mrs. Ramsayn ja perheen Nancy-tyttären kokemukset ihmisestä tyhjänä liittynevät modernistien käsitykseen henkilöhahmosta. Mrs. Ramsay ja Lily Briscoe käyttävät kumpikin tyhjyyttä luovana tilana, Lily tekee sen vain konkreettisemmin taistellessaan tyhjän maalauspohjan kanssa. Lily kokee myös voimakasta tyhjyyttä menetettyään Mrs. Ramsayn, jonka hän näkee aarrearkun kaltaisena toisin kuin vaimoaan vähättelevä Mr. Ramsay. Tarkastelen tutkielmassani fiktiivisen maailman rakennettuja tiloja. Woolf kertoo tarinaansa taloa täyttäen ja tyhjentäen. Teen havaintoja esimerkiksi talon, portaiden tai kahvikupin tyhjyydestä. Näkökulmani tyhjyyteen on siis arkkitehtoninen. Stephen Kern kirjoittaa teoksessaan The Modernist Novel: A Critical Introduction (2011) siitä, miten 1800-luvun lopulla aiemmin negatiivisesti käsitettyjä elementtejä hyödynnettiinkin positiivisina (76). Kernin lisäksi hyödynnän tutkielmassani monien muiden kirjallisuudentutkijoiden ajatuksia. Näen tyhjyyden kohdeteoksessani kerronnallisesti hyödynnettynä elementtinä, joka on välttämätön osa sen elinvoimaisuutta

The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α

Publisher Copyright: © 2022, The Author(s).Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.Peer reviewe

Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor alpha Antagonist Infliximab in Pediatric Inflammatory Bowel Disease

Background The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease. Methods We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value Results At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline. Conclusions High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes. Lay Summary We studied absolute and relative abundances of fecal microbiota in relation to response to induction therapy with infliximab in pediatric inflammatory bowel disease. We discovered that a high absolute abundance of anti-inflammatory Bifidobacteriales at baseline associated with response.Peer reviewe

Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease

Background and aimsSubjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate.Subjects and methodsWe recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected.ResultsPatients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn's disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD.ConclusionsFecal microbiota in CLD is different from that of healthy subjects or Crohn's disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.Peer reviewe

Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease

BACKGROUND: The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease. METHODS: We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts. RESULTS: At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline. CONCLUSIONS: High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.publishedVersionPeer reviewe

Development of specific adsorbents for human tumor necrosis factor-alpha: Influence of antibody immobilization on performance and biocompatibility

To develop adsorbents for the specific removal of tumor necrosis factor-alpha (TNF) in extracorporeal blood purification, cellulose microparticles were functionalized either with a monoclonal anti-TNF antibody (mAb) or with recombinant human antibody fragments (Fab). The TNF binding capacity of the adsorbents was determined with in vitro batch experiments using spiked human plasma (spike: 1200 pg TNF/mL; 1 mg particles in 250 mu L plasma). Random immobilization of the full-sized monoclonal antibody to periodate-activated cellulose yielded particles with excellent adsorption capacity (258.1 +/- 48.6 pg TNF per mg adsorbent wet weight). No leaching of antibody was detectable, and the adsorbents retained their activity for at least 12 months at 4 degrees C. We found that the conditions used during immobilization of the antibody (pH, nature of the reducing agent) profoundly influenced the biocompatibility of the resulting adsorbents, especially with respect to activation of the complement system. Particles obtained by random immobilization of the monovalent Fab fragments on periodate-activated cellulose using the same conditions as for immobilization of the mAb exhibited only low adsorption capacity (44 +/- 7 pg/mg adsorbent wet weight). Oriented coupling of the Fab fragments on chelate-epoxy cellulose via a C-terminal histidine tag, however, increased the adsorption capacity to 178.3 +/- 8.6 pg TNF/mg adsorbent wet weight. Thus, in the case of small, monovalent ligands, the orientation on the carrier is critical to retain full binding activity