Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ? 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ? 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD

False positive circumsporozoite protein ELISA: a challenge for the estimation of the entomological inoculation rate of malaria and for vector incrimination

<p>Abstract</p> <p>Background</p> <p>The entomological inoculation rate (EIR) is an important indicator in estimating malaria transmission and the impact of vector control. To assess the EIR, the enzyme-linked immunosorbent assay (ELISA) to detect the circumsporozoite protein (CSP) is increasingly used. However, several studies have reported false positive results in this ELISA. The false positive results could lead to an overestimation of the EIR. The aim of present study was to estimate the level of false positivity among different anopheline species in Cambodia and Vietnam and to check for the presence of other parasites that might interact with the anti-CSP monoclonal antibodies.</p> <p>Methods</p> <p>Mosquitoes collected in Cambodia and Vietnam were identified and tested for the presence of sporozoites in head and thorax by using CSP-ELISA. ELISA positive samples were confirmed by a <it>Plasmodium </it>specific PCR. False positive mosquitoes were checked by PCR for the presence of parasites belonging to the Haemosporidia, Trypanosomatidae, Piroplasmida, and Haemogregarines. The heat-stability and the presence of the cross-reacting antigen in the abdomen of the mosquitoes were also checked.</p> <p>Results</p> <p>Specimens (N = 16,160) of seven anopheline species were tested by CSP-ELISA for <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>(Pv210 and Pv247). Two new vector species were identified for the region: <it>Anopheles pampanai </it>(<it>P. vivax</it>) and <it>Anopheles barbirostris </it>(<it>Plasmodium malariae</it>). In 88% (155/176) of the mosquitoes found positive with the <it>P. falciparum </it>CSP-ELISA, the presence of <it>Plasmodium </it>sporozoites could not be confirmed by PCR. This percentage was much lower (28% or 5/18) for <it>P. vivax </it>CSP-ELISAs. False positive CSP-ELISA results were associated with zoophilic mosquito species. None of the targeted parasites could be detected in these CSP-ELISA false positive mosquitoes. The ELISA reacting antigen of <it>P. falciparum </it>was heat-stable in CSP-ELISA true positive specimens, but not in the false positives. The heat-unstable cross-reacting antigen is mainly present in head and thorax and almost absent in the abdomens (4 out of 147) of the false positive specimens.</p> <p>Conclusion</p> <p>The CSP-ELISA can considerably overestimate the EIR, particularly for <it>P. falciparum </it>and for zoophilic species. The heat-unstable cross-reacting antigen in false positives remains unknown. Therefore it is highly recommended to confirm all positive CSP-ELISA results, either by re-analysing the heated ELISA lysate (100°C, 10 min), or by performing <it>Plasmodium </it>specific PCR followed if possible by sequencing of the amplicons for <it>Plasmodium </it>species determination.</p

Developmental expression of COE across the Metazoa supports a conserved role in neuronal cell-type specification and mesodermal development

The transcription factor COE (collier/olfactory-1/early B cell factor) is an unusual basic helix–loop–helix transcription factor as it lacks a basic domain and is maintained as a single copy gene in the genomes of all currently analysed non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its proposed ancestral role in the specification of chemosensory neurons and the wealth of functional data from vertebrates and Drosophila, the evolutionary history of the COE gene can be readily investigated. We have examined the ways in which COE expression has diversified among the Metazoa by analysing its expression from representatives of four disparate invertebrate phyla: Ctenophora (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we have studied COE function with knockdown experiments in S. purpuratus, which indicate that COE is likely to be involved in repressing serotonergic cell fate in the apical ganglion of dipleurula larvae. These analyses suggest that COE has played an important role in the evolution of ectodermally derived tissues (likely primarily nervous tissues) and mesodermally derived tissues. Our results provide a broad evolutionary foundation from which further studies aimed at the functional characterisation and evolution of COE can be investigated

Myötätunto lasten vertaiskulttuurissa

Peers have a significant impact on children’s learning and development (e.g., Rubin, Bukowski & Bowker, 2015; Sawyer, 2015; Corsaro & Eder, 1990). Interactions with other same age children not only influence children’s social, cognitive and emotional competencies, but importantly constitute the very grounds for their development. Previous research has shown that peers have a critical role in children’s language learning, cognitive skills, physical wellbeing as well as in socio-cognitive areas of development, like collaboration, cooperation and pro-sociality. While this body of work has significantly advanced our understanding of the nature of peer interactions, there is still a dearth of knowledge on how children orient to and address the worries, concerns or suffering of their peers in everyday settings, namely, to act with compassion. To this end, in this chapter we will present our cultures of compassion approach (Lipponen, Rajala, & Hilppö, 2018) to studying compassion in children’s peer interactions in a Finnish kindergarten and share an example of our video ethnographic work and interaction analysis on compassion. We will conclude our chapter by discussing how it is possible to foster compassionate peer cultures in early child education and care settings.eers have a significant impact on children’s learning and development (e.g., Rubin, Bukowski & Bowker, 2015; Sawyer, 2015; Corsaro & Eder, 1990). Interactions with other same-age children not only influence children’s social, cognitive and emotional competencies, but importantly constitute the very grounds for their development. Previous research has shown that peers have a critical role in children’s language learning, cognitive skills, physical wellbeing as well as in socio-cognitive areas of development, like collaboration, cooperation and pro-sociality. While this body of work has significantly advanced our understanding of the nature of peer interactions, there is still a dearth of knowledge on how children orient to and address the worries, concerns or sufferings of their peers in everyday settings, namely, to act with compassion. To this end, in this chapter we will present our cultures of compassion approach (Lipponen et al., 2018) to studying compassion in children’s peer interactions in a Finnish kindergarten and share an example of our video ethnographic work and interaction analysis on compassion. We will conclude our chapter by discussing how it is possible to foster compassionate peer cultures in early child education and care settings.Peer reviewe

Preservice Teachers\u27 Strategies for Teaching Mathematics with English Learners

Although English learners (ELs) are one of the fastest growing groups of students in the United States, many teacher preparation programs have yet to require preservice teachers (PSTs) to receive training in effective practices for teaching ELs. We examined four elementary PSTs’ instructional practices when implementing cognitively demanding mathematics tasks with ELs during a 4-week field experience. Through interviews, observations, and written reflections, we found that the PSTs tried to support the ELs, with varying degrees of success, by allowing for multiple modes of communication, including visual supports, pressing for explanations, and checking for understanding. The PSTs’ use of these strategies during the field experience was largely in response to the ELs’ use of language rather than mathematics. Furthermore, although the PSTs’ attention to linguistic supports was well intentioned, it often resulted in the PSTs taking on much of the mathematical thinking or failing to consider different student mathematical conceptions. We conclude that explicit instruction in and reflection on effective instructional strategies with ELs, set in authentic experiences, could help PSTs to more effectively develop the knowledge and skills necessary to meet the needs of ELs in the mathematics classroom

Who is the Hybrid Teacher Educator? Understanding professional identity in school-university partnership

Teacher education has long been criticised for a perceived disconnect between university-based and school-based learning, and literature often proposes closer integration of these two spaces as central to bridging this disconnect (Allen and Wright in Teachers Teach Theory Pract 20:136151, 2014; Darling-Hammond in J Teacher Educ 57:300314, 2006); third space theory is one way to frame this integration (Zeichner in Educ Researcher 28:415, 2010). Third space theory provides a theoretical premise that has the potential to reconceptualise the connection between universities and schools through disrupting binaries and encouraging the continual negotiation and reinterpretation of identities (Bhabha in The location of culture. Routledge, London, 1994). Through reconceptualising the spaces of, and between, schools and universities, third space theory encourages new ways of thinking about partnerships, shared knowledge and ways of working, and in doing so creates hybrid roles which challenge traditional roles or positions within both spaces. Drawing on interviews with several hybrid teacher educators, this chapter discusses the fluid roles and responsibilities of these emerging roles and considers implications for shifting professional identities in teacher education

Who is the Hybrid Teacher Educator? Understanding Professional Identity in School-University Partnership

Teacher education has long been criticised for a perceived disconnect between university-based and school-based learning, and literature often proposes closer integration of these two spaces as central to bridging this disconnect (Allen and Wright in Teachers Teach Theory Pract 20:136–151, 2014; Darling-Hammond in J Teacher Educ 57:300–314, 2006); third space theory is one way to frame this integration (Zeichner in Educ Researcher 28:4–15, 2010). Third space theory provides a theoretical premise that has the potential to reconceptualise the connection between universities and schools through disrupting binaries and encouraging the continual negotiation and reinterpretation of identities (Bhabha in The location of culture. Routledge, London, 1994). Through reconceptualising the spaces of, and between, schools and universities, third space theory encourages new ways of thinking about partnerships, shared knowledge and ways of working, and in doing so creates hybrid roles which challenge traditional roles or positions within both spaces. Drawing on interviews with several hybrid teacher educators, this chapter discusses the fluid roles and responsibilities of these emerging roles and considers implications for shifting professional identities in teacher education