Shiga Toxin-Mediated Hemolytic Uremic Syndrome: Time to Change the Diagnostic Paradigm?

Hemolytic uremic syndrome (HUS) is caused by enterohemorrhagic Escherichia coli (EHEC) which possess genes encoding Shiga toxin (stx), the major virulence factor, and adhesin intimin (eae). However, the frequency of stx-negative/eae-positive E. coli in stools of HUS patients and the clinical significance of such strains are unknown.Between 1996 and 2006, we sought stx-negative/eae-positive E. coli in stools of HUS patients using colony blot hybridization with the eae probe and compared the isolates to EHEC causing HUS. stx-negative/eae-positive E. coli were isolated as the only pathogens from stools of 43 (5.5%) of 787 HUS patients; additional 440 (55.9%) patients excreted EHEC. The majority (90.7%) of the stx-negative/eae-positive isolates belonged to serotypes O26:H11/NM (nonmotile), O103:H2/NM, O145:H28/NM, and O157:H7/NM, which were also the most frequent serotypes identified among EHEC. The stx-negative isolates shared non-stx virulence and fitness genes with EHEC of the corresponding serotypes and clustered with them into the same clonal complexes in multilocus sequence typing, demonstrating their close relatedness to EHEC.At the time of microbiological analysis, approximately 5% of HUS patients shed no longer the causative EHEC, but do excrete stx-negative derivatives of EHEC that lost stx during infection. In such patients, the EHEC etiology of HUS is missed using current methods detecting solely stx or Shiga toxin; this can hamper epidemiological investigations and lead to inappropriate clinical management. While maintaining the paradigm that HUS is triggered by Shiga toxin, our data demonstrate the necessity of considering genetic changes of the pathogen during infection to adapt appropriately diagnostic strategies

The effect of school consolidation on student achievement.

Many countries have seen a substantial increase in the average school size over the past decades, and a corresponding reduction in the number of schools. It has been widely argued that both students and local communities have suffered from these consolidations. Despite their vast extent and controversy, the literature is scarce with evidence of how consolidation affects performance of exposed students. This study explores how consolidation of 76 rural lower secondary schools in Norway affects students' educational performance, using rich register data. I find no indication that school consolidation reduces educational achievement. Nonetheless, the analysis suggests a negative association between school closure and grade point average, but this effect appears to be driven by lenient grading in small schools

Publication bias in the returns to R&D literature

The returns to R&D literature is large and has been surveyed on several occasions. We complement previous surveys by using formal meta analytic techniques to analyse publication bias. We find evidence consistent with a strong positive bias in the part of the literature that controls for unobserved firm fixed effects. The reason may be that fixed effects specifications are particularly susceptible to measurement errors and therefore have a high probability of producing implausibly low return estimates. Implausible estimates are likely to be filtered out before being reported, and our analysis suggest that 26 % of a hypothetical complete literature is missing. Future reviews should take into account that the full effect of negative specifications biases may be masked by reporting and publication bias

Tregheter i arbeidsmarkedet : teori om virkninger av faste kostnadskomponenter, og empiriske resultater for aggregerte sammenhenger

I den teoretiske delen av denne oppgaven drøfter jeg hvordan ulike kostnadskomponenter knyttet til variasjoner i antall ansatte kan føre til tregheter i bedriftenes respons på eksogene sjokk. Kostnader ved justert bemanning kan være knyttet til ansettelser, opplæring og oppsigelser av ansatte. Som en utvidelse av teoretisk analyse har jeg også gjennomført en tilnærming med numeriske simuleringer av bedriftsatferd. Her ble hovedkonklusjonen at treghetene som følger av faste kostnadskomponenter er betydelige for rimelige verdier på slike kostnader. I den empiriske tilnærmingen brukte jeg aggregerte data for produksjon og arbeidsledighet til å teste for eventuelle observerte tregheter mellom ulike variable for aktiviteten i arbeidsmarkedet. Basert på nye norske data bekreftes de treghetene som kommer til uttrykk gjennom Okuns lov, mens det er vanskeligere å dokumentere eventuelle stabile tregheter i samvariasjonen mellom produksjon og sysselsetting

Har kvaliteten på lærere falt over tid?

-With persmission from publisher, FagbokforlagetBekymringer om opptakskravene til lærerstudiet er et tilbakevendende tema i offentlig debatt, og myndighetene har også forsøkt ulike tiltak for å bedre rekrutteringen. Det er derfor interessant å studere de lange linjene i rekrutteringen til læreryrket. Vi analyserer hvordan de som søker seg til læreryrket, har prestert på kognitive tester brukt ved sesjon. Vi finner at gjennomsnittlig skår for mannlige lærere har falt ti persentiler fra lærerårskullet født i 1950 til lærerårskullet født i 1980. I tillegg har andelen av undervisningspersonalet med lektorkompetanse i allmennfaglig studieretning falt dramatisk. Fallet er spesielt sterkt for realister. Vi finner videre at fallet i kognitiv skår har kommet parallelt med et fall i relative lønninger for lærere og lektorer. Vi viser dessuten at flere forlater læreryrket i gode tider, når utvalget av godt betalte jobber er større. Videre forskning må til for å avklare om fallet i kognitiv skår kan knyttes kausalt til lønnsutviklingen, og ikke minst om det målte kvalitetsfallet har hatt betydning for elevenes læring

Brain Development after Neonatal Intermittent Hyperoxia-Hypoxia in the Rat Studied by Longitudinal MRI and Immunohistochemistry

Background: Neonatal intermittent hyperoxia-hypoxia (IHH) is involved in the pathogenesis of retinopathy of prematurity. Whether similar oxygen fluctuations will create pathological changes in the grey and white matter of the brain is unknown. Methods: From birth until postnatal day 14 (P14), two litters (total n = 22) were reared in IHH: hyperoxia (50% O2) interrupted by three consecutive two-minute episodes of hypoxia (12% O2) every sixth hour. Controls (n = 8) were reared in room-air (20.9% O2). Longitudinal MRI (Diffusion Tensor Imaging and T2-mapping) was performed on P14 and P28 and retinal and brain tissue were examined for histopathological changes. Long-term neurodevelopment was assessed on P20 and P27. Results: Mean, radial and axial diffusivity were higher in white matter of IHH versus controls at P14 (p < 0.04), while fractional anisotropy (FA) was lower in the hippocampal fimbria and tended to be lower in corpus callosum (p = 0.08) and external capsule (p = 0.05). White matter diffusivity in IHH was similar to controls at P28. Higher cortical vessel density (p = 0.005) was observed at P14. Cortical and thalamic T2-relaxation time and mean diffusivity were higher in the IHH group at P14 (p ≤ 0.03), and albumin leakage was present at P28. Rats in the IHH group ran for a longer time on a Rotarod than the control group (p ≤ 0.005). Pups with lower bodyweight had more severe MRI alterations and albumin leakage. Conclusion: IHH led to subtle reversible changes in brain white matter diffusivity, grey matter water content and vascular density. However, alterations in blood-brain barrier permeability may point to long-term effects. The changes seen after IHH exposure were more severe in animals with lower bodyweight and future studies should aim at exploring possible interactions between IHH and growth restriction

Brain Development after Neonatal Intermittent Hyperoxia-Hypoxia in the Rat Studied by Longitudinal MRI and Immunohistochemistry

Background: Neonatal intermittent hyperoxia-hypoxia (IHH) is involved in the pathogenesis of retinopathy of prematurity. Whether similar oxygen fluctuations will create pathological changes in the grey and white matter of the brain is unknown. Methods: From birth until postnatal day 14 (P14), two litters (total n = 22) were reared in IHH: hyperoxia (50% O2) interrupted by three consecutive two-minute episodes of hypoxia (12% O2) every sixth hour. Controls (n = 8) were reared in room-air (20.9% O2). Longitudinal MRI (Diffusion Tensor Imaging and T2-mapping) was performed on P14 and P28 and retinal and brain tissue were examined for histopathological changes. Long-term neurodevelopment was assessed on P20 and P27. Results: Mean, radial and axial diffusivity were higher in white matter of IHH versus controls at P14 (p < 0.04), while fractional anisotropy (FA) was lower in the hippocampal fimbria and tended to be lower in corpus callosum (p = 0.08) and external capsule (p = 0.05). White matter diffusivity in IHH was similar to controls at P28. Higher cortical vessel density (p = 0.005) was observed at P14. Cortical and thalamic T2-relaxation time and mean diffusivity were higher in the IHH group at P14 (p ≤ 0.03), and albumin leakage was present at P28. Rats in the IHH group ran for a longer time on a Rotarod than the control group (p ≤ 0.005). Pups with lower bodyweight had more severe MRI alterations and albumin leakage. Conclusion: IHH led to subtle reversible changes in brain white matter diffusivity, grey matter water content and vascular density. However, alterations in blood-brain barrier permeability may point to long-term effects. The changes seen after IHH exposure were more severe in animals with lower bodyweight and future studies should aim at exploring possible interactions between IHH and growth restriction

Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles

The blood–brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system (CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS