Cosmological models from quintessence

A generalized quintessence model is presented which corresponds to a richer vacuum structure that, besides a time-dependent, slowly varying scalar field, contains a varying cosmological term. From first principles we determine a number of scalar-field potentials that satisfy the constraints imposed by the field equations and conservations laws, both in the conventional and generalized quintessence models. Besides inverse-power law solutions, these potentials are given in terms of hyperbolic functions or the twelve Jacobian elliptic functions, and are all related to the luminosity distance by means of an integral equation. Integration of this equation for the different solutions leads to a large family of cosmological models characterized by luminosity distance-redshift relations. Out of such models, only four appear to be able to predict a required accelerating universe conforming to observations on supernova Ia, at large or moderate redshifts.Comment: 9 pages, RevTex, to appear in Phys. Rev.

Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial

Summary Background Human African trypanosomiasis caused by Trypanosoma brucei gambiense (gambiense HAT) in patients with late-stage disease requires hospital admission to receive nifurtimox-eflornithine combination therapy (NECT). Fexinidazole, the latest treatment that has been recommended by WHO, also requires systematic admission to hospital, which is problematic in areas with few health-care resources. We aim to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT. Methods This multicentre, prospective, open-label, single-arm, phase 2/3 study recruited patients aged 15 years or older with confirmed gambiense HAT infection from ten hospitals in the Democratic Republic of the Congo and Guinea. Inclusion criteria included a Karnofsky score less than 50, ability to swallow tablets, a permanent address or traceability, ability to comply with follow-up visits and study requirements, and agreement to hospital admission during treatment. Oral acoziborole was administered as a single 960 mg dose (3 × 320 mg tablets) to fasted patients. Patients were observed in hospital until day 15 after treatment administration then for 18 months as outpatients with visits at 3, 6, 12, and 18 months. The primary efficacy endpoint was the success rate of acoziborole treatment at 18 months in patients with late-stage gambiense HAT (modified intention-to-treat [mITT] population), based on modified WHO criteria. A complementary post-hoc analysis comparing the 18-month success rates for acoziborole and NECT (using historical data) was performed. This study is registered at ClinicalTrials.gov, NCT03087955. Findings Between Oct 11, 2016, and March 25, 2019, 260 patients were screened, of whom 52 were ineligible and 208 were enrolled (167 with late-stage and 41 with early-stage or intermediate-stage gambiense HAT; primary efficacy analysis set). All 41 (100%) patients with early-stage or intermediate-stage and 160 (96%) of 167 with late-stage disease completed the last 18-month follow-up visit. The mean age of participants was 34·0 years (SD 12·4), including 117 (56%) men and 91 (44%) women. Treatment success rate at 18 months was 95·2% (95% CI 91·2-97·7) reached in 159 of 167 patients with late-stage gambiense HAT (mITT population) and 98·1% (95·1-99·5) reached in 159 of 162 patients (evaluable population). Overall, 155 (75%) of 208 patients had 600 treatment-emergent adverse events. A total of 38 drug-related treatment-emergent adverse events occurred in 29 (14%) patients; all were mild or moderate and most common were pyrexia and asthenia. Four deaths occurred during the study; none were considered treatment related. The post-hoc analysis showed similar results to the estimated historical success rate for NECT of 94%. Interpretation Given the high efficacy and favourable safety profile, acoziborole holds promise in the efforts to reach the WHO goal of interrupting HAT transmission by 2030. Funding Bill & Melinda Gates Foundation, UK Aid, Federal Ministry of Education and Research, Swiss Agency for Development and Cooperation, Médecins Sans Frontières, Dutch Ministry of Foreign Affairs, Norwegian Agency for Development Cooperation, Norwegian Ministry of Foreign Affairs, the Stavros Niarchos Foundation, Spanish Agency for International Development Cooperation, and the Banco Bilbao Vizcaya Argentaria Foundation. Translation For the French translation of the abstract see Supplementary Materials section

Vernier enhanced Mach Zehnder interferometer for dissolved methane detection

In this thesis the theory describing a vernier enhanced Mach Zehnder interferometer for detecting dissolved methane is discussed. A method for effectively simulating photonic components, with features ranging from centimeter to nanometer scale using COMSOL is demonstrated. The method is then used to simulate the behaviour of a vernier enhanced sensor. Based on the simulations, a methane sensitive sensor using the vernier concept is presented. The proposed sensor has a limit of detection as low as 9.34 10^(-6) RIU and overall sensitivity of 326 um/RIU, and should detect concentrations of dissolved methane less than 50 nM . The feasibility of producing a prototype in NTNU Nanolab have also been investigated. Both straight waveguides, ring resonators and five MZI's with Y-bends has been fabricated on an silicon-on-insulator (SOI) platform. The processes used includes plasma enhanced chemical vapor deposition (PECVD), electron beam lithography (EBL), inductively coupled plasma reactive ion etch (ICP-RIE) and a scanning tunneling electron microscope (S(T)EM) for characterization. Some of the fabricated components are also tested in an optics lab. Based on characterisation using S(T)EM, the SOI platform with a thermally grown oxide layer is concluded to be the favourable choice for fabricating a prototype sensor in the future

Mitochondrial DNA is a danger to the heart

Myocardial infarction remains a major killer world-wide. The preservation of cardiac muscle cells is critical to patient outcomes after myocardial infarction. During myocardial infarction, cardiac muscle cells die and release cellular components that may cause inflammation and damage viable heart tissue. Mitochondrial DNA (mtDNA) is one of the potentially damaging components. The aim of this thesis was to improve understanding of the potentially harmful role of mtDNA in the setting of myocardial infarction. This was based on a patient study and a series of animal and cell experiments. We found that patients with myocardial infarction have elevated levels of mtDNA in their blood and that the heart is a likely source. mtDNA from patients induced an inflammatory reaction in cells and also triggered inflammation in mice. Further, we found that mtDNA induced cardiac cell death and impaired mitochondrial function. We also found that the protein nucleolin, which is expressed on the cell membrane of cardiomyocytes, could be a possible route for internalization of potentially damaging mtDNA and thus a potential treatment option

Virkemidler for å øke retesting etter klamydiabehandling ved Sex og samfunn fra 30 til 80 % i løpet av seks måneder

Bakgrunn: Sex og samfunn er en klinikk for ung helse i Oslo, som utførte 4806 (75 % jenter) klamydiatester i 2010, hvorav 634 (68 % jenter) var positive. Den faglige og administrative ledelsen ønsker å kalle inn alle pasienter som har vært behandlet for genital klamydiainfeksjon til kontroll 5-6 uker etter behandling for ny testing for å utelukke reinfeksjon og undersøke behandlingseffektivitet. Det siste er særlig viktig da klinikken planlegger en randomisert, kontrollert studie med sammenligning av to behandlingsopplegg. I fjor var oppmøteandelen til kontrolltime 30 prosent – for lav for å kunne gjennomføre en slik undersøkelse. Det kliniske problem i denne oppgaven er den lave oppmøteandelen til kontrolltime etter behandling for genital klamydiainfeksjon ved Sex og samfunn. Gjeldende praksis er at pasienten anmodes om å komme til kontroll etter 5-6 uker. Kunnskapsgrunnlag: Kunnskapsgrunnlaget er todelt: Prosjektgruppen har innhentet retningslinjer vedrørende retesting etter behandling for genital klamydiainfeksjon og kunnskap om tiltak som kan øke oppmøteandel til legetimer. I amerikanske og britiske retningslinjer er det ikke anbefalt å gjøre såkalt test-of-cure etter klamydiabehandling, men det er derimot anbefalt å gjøre retesting for å utelukke reinfeksjon 3-12 måneder etter behandling. Upubliserte norske data og nødvendigheten av økt retestandel for å kunne gjennomføre planlagt randomisert, kontrollert studie kan likevel begrunne intervensjon for å øke retestandel 5-6 uker etter behandling for genital klamydiainfeksjon ved Sex og samfunn. Tiltak og kvalitetsindikator: Prosjektgruppen anbefaler innføring av en sjekkliste (check-do) som behandlerne skal bruke under behandlingskonsultasjon for genital klamydiainfeksjon som inneholder følgende punkter: (1) Bestilling av kontrolltime, (2) sikring av kontaktinformasjon til pasienten, (3) registrering i liste for påminnelse per SMS/telefon dagen før kontrolltime og (4) pasientinformasjon hvor viktigheten av retest klargjøres. Dagen før den avtalte kontrolltimen blir pasienten påminnet timen av en sykepleier per SMS/telefon. Effekten av tiltakene evalueres med (1) andel av behandlings-konsultasjonene hvor sjekklisten brukes og (2) andel av pasienter behandlet for genital klamydiainfeksjon som møter til kontrolltime (begge prosessindikatorer) etter 3, 4, 5 og 6 måneder. Organisering/ledelse: Prosjektgruppen har et medlem som arbeider ved Sex og samfunn og har vært i kontakt med faglig og administrativ ledelse og opplever at ønske om endring er godt forankret i ledelsen, som vil drive implementeringen av forbedringsprosjektet. Prosjektgruppen anbefaler at endringene implementeres i henhold til Kotters åtte punkter for endringsledelse. Vurdering: Forbedringsprosjektet tar utgangspunkt i et klinisk mikrosystem for ung helse og søker å forbedre en del av gjeldende praksis som ledelse og behandlere anser som et problem. De foreslåtte tiltakene er enkle, tar liten tid, og søker å redusere de barrierer mot oppmøte til kontrolltime prosjektgruppen har identifisert. Tiltakene bærer liten kostnad og prosessindikatorene er reliable og valide og, gitt god effekt av tiltakene vil Sex og samfunn kunne bidra til fremskaffing av ny, potensielt retningslinjeendrende kunnskap om antibiotikabehandling ved genital klamydiainfeksjon

60% Reduction of reoperations and complications for elderly patients with hip fracture through the implementation of a six-item improvement programme

Introduction Hip fractures are common, serious and costly fractures in the elderly population. Several guidelines seeking to ensure best practice have been introduced. Although our institution complied with national guidelines for early surgery of hip fractures, no assessment of other evidence-based measures existed. We wanted to assess, test, implement and measure the impact of a quality improvement (QI) programme consisting of key elements proven to be important in the treatment of hip fractures. Methods We formed a multidisciplinary QI team, consisting of several specialists in different fields. The QI team assessed multiple possible process measures for inclusion in the programme and selected six measurable interventions for implementation: early surgery, correct administration of prophylactic antibiotics, surgery using proven methods and expertise, a multidisciplinary patient pathway and secondary fracture prevention. The improvement process was monitored by a statistical process control chart (SPC). Complications, reoperations and mortality were compared before (n=293) and after (n=182) the intervention. Results The SPC analyses indicated increasing adherence with all interventions throughout the improvement programme, and sustainability 7 years later. The last four periods showed a stable adherence above 90%. We found 60% reduction in major complications after the implementation of the improvement programme, from 19.1% to 7.7% (HR: 0.38 (95% CI: 0.23 to 0.61, p=0.0007). The need for reoperations due to complications fell from 12.6% to 4.9% (HR: 0.37 (95% CI: 0.21 to 0.67, p=0.0054). We did not find a difference in post-operative mortality after the implementation of the QI programme (HR: 0.95 (95% CI: 0.74 to 1.2, p=0.645). Conclusion Our multiprofessional improvement programme achieved almost full adherence within 2 years and was sustainable 7 years later. The quality and safety of the care process were improved and led to a substantial and sustainable decrease in complications and reoperations

Inhibiting nucleolin reduces inflammation induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and reoxygenation

Background and purpose Cellular debris causes sterile inflammation after myocardial infarction. Mitochondria constitute about 30 percent of the human heart. Mitochondrial DNA (mtDNA) is a damage‐associated‐molecular‐pattern that induce injurious sterile inflammation. Little is known about mtDNA's inflammatory signalling pathways in cardiomyocytes and how mtDNA is internalized to associate with its putative receptor, toll‐like receptor 9 (TLR9). Experimental Approach We hypothesized that mtDNA can be internalized in cardiomyocytes and induce an inflammatory response. Adult mouse cardiomyocytes were exposed to hypoxia‐reoxygenation and extracellular DNA. Microscale thermophoresis was used to demonstrate binding between nucleolin and DNA. Key results Expression of the pro‐inflammatory cytokines IL‐1β and TNFα were upregulated by mtDNA, but not by nuclear DNA (nDNA), in cardiomyocytes exposed to hypoxia‐reoxygenation. Blocking the RNA/DNA binding protein nucleolin with midkine reduced expression of IL‐1β/TNFα and the nucleolin inhibitor AS1411 reduced interleukin‐6 release in adult mouse cardiomyocytes. mtDNA bound 10‐fold stronger than nDNA to nucleolin. In HEK293‐NF‐κB reporter cells, mtDNA induced NF‐κB activity in normoxia, while CpG‐DNA and hypoxia‐reoxygenation, synergistically induced TLR9‐dependent NF‐κB activity. Protein expression of nucleolin was found in the plasma membrane of cardiomyocytes and inhibition of nucleolin with midkine inhibited cellular uptake of CpG‐DNA. Inhibition of endocytosis did not reduce CpG‐DNA uptake in cardiomyocytes. Conclusion and implications mtDNA, but not nDNA, induce an inflammatory response in mouse cardiomyocytes during hypoxia‐reoxygenation. In cardiomyocytes, nucleolin is expressed on the membrane and blocking nucleolin reduce inflammation. Nucleolin might be a therapeutic target to prevent uptake of immunogenic DNA and reduce inflammation

Ventilasjonsstøtte for hypoksemiske intensivpasienter med covid-19

BAKGRUNN Covid-19-pneumoni kan gi alvorlig hypoksemisk respirasjonssvikt som krever intensivmedisinsk behandling. Vi ønsket å beskrive covid-19-intensivpasienter som ble behandlet med og uten invasiv ventilasjonsstøtte. MATERIALE OG METODE Materialet er hentet fra lokalt kvalitetsregister og består av data om pasienter med covid-19 innlagt på intensivavdelingen ved Oslo universitetssykehus, Ullevål i perioden 5.3–28.5.2020. Pasientene ble kategorisert i tre grupper basert på respirasjonssviktbehandlingen (oksygen alene, tillegg av ikke-invasiv ventilasjonsstøtte (NIV) og intubasjon/respirator) og beskrevet med deskriptiv statistikk. RESULTATER Av 165 innlagte covid-19-pasienter ble 26 (16 %) behandlet ved vår intensivavdeling. Fire av disse hadde behandlingsbegrensninger og ble ekskludert. De 22 pasientene inkludert i denne studien hadde gjennomsnittsalder 56 år (spredning 25–78 år), 17 (77 %) var menn. Elleve pasienter fikk respiratorbehandling, syv oksygen på maske og fire tillegg av ikke-invasiv ventilasjonsstøtte. I respiratorgruppen var to døde per 28.5.2020, resten var skrevet ut av intensivavdelingen i live, hvorav én fortsatt lå på sengepost. Alle pasienter behandlet med oksygen og ikke-invasiv ventilasjonsstøtte var i live og utskrevet fra sykehus. FORTOLKNING Mange pasienter med covid-19-respirasjonssvikt og behov for intensivbehandling kan klare seg med økt oksygentilbud og ikke-invasiv ventilasjonsstøtte, men behov for intubasjon må fortløpende vurderes. Over 90 % av aktivt behandlede intensivpasienter overlevde