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Statistical stressor-response models are a common approach to derive biologically relevant water quality criteria for the management of waterbody health. These types of models are typically derived at state-wide or ecoregional scales and consequently incorporate a large amount of natural and disturbance-related variability that may obscure the relationship that one is interested in quantifying. We demonstrate an alternative approach termed “reach-specific modeling” to identify potential biological response thresholds to eutrophication in the Santa Margarita River watershed (California, U.S.A.). Individual models of benthic invertebrate response to eutrophication stress were created for both bioassessment sampling sites and NHD + stream-segments in the watershed (46 sites, 832 segments). Each model was built using only data from environmentally similar sites from a state-wide dataset to minimize variation from natural environmental gradients, while allowing eutrophication stress to vary. Thresholds of potential biological impact were extracted from each stressor-response model. Across the whole watershed thresholds varied from location-to-location: total nitrogen (1.14–1.26 mg L-1 TN), total phosphorus (0.12–0.15 mg L-1 TP), benthic algal biomass (29–39 mg m−2 benthic chl-a), and benthic ash-free dry mass (2.5––3.0 mg cm−2 AFDM). Notably, nearly all of the thresholds derived from these reach-specific models were ∼10–90 % higher than those from a similar state-wide model. Furthermore, there were a number of spatial groupings of thresholds for each eutrophication indicator across the watershed, suggesting reach-scale natural gradients in hydrogeomorphology and natural land cover type may mediate the stressor-biology interaction. Reach-scale models tended to have better fits than their state-wide counterparts, but had equivalent or slightly worse accuracy. The reach-specific approach to threshold development illustrates that the biological response to stress is likely not uniform within a single system, much less between systems. As a consequence, this approach can allow managers to identify systems that are more sensitive or resistant to a given stressor across diverse landscapes and make better informed decisions on their management accordingly.

Background Recent reviews of sudden unexpected deaths in infancy (SUDI) in England recommend a multiagency working (MAW) approach to prevention but lack clear guidance around how this might be implemented.Aims In England, local authorities commission and oversee public health services. This review examines how local authority policies address implementation of MAW for SUDI prevention to understand local variations and identify strengths and weaknesses.Methods Using a comprehensive list of all metropolitan, county, unitary councils and London boroughs in England, we systematically searched local authority websites for relevant published documents and submitted freedom of information (FOI) requests where policies or guidance for SUDI prevention had not been sourced online. We extracted data from documents using a standardised form to summarise policy contents which were then collated, described and appraised.Findings We searched the websites of 152 council and London boroughs, identifying 36 relevant policies and guidelines for staff. We submitted 116 FOI requests which yielded 64 responses including six valid documents: 45% (52/116) of local authorities did not respond. Seventeen councils shared the same guidance under safeguarding partnerships; removal of duplicates resulted in 26 unique documents. Only 15% (4/26) of the documents included a detailed plan for how MAW approaches were to be implemented despite 73% (19/26) of the documents mentioning the importance of engaging the MAW in raising awareness of safe sleep for babies with vulnerable families. Five areas of variation were identified across policies: (1) scope, (2) responsibilities, (3) training, (4) implementation and (5) evaluation.Conclusions There are discrepancies between local authorities in England in whether and how MAW for SUDI prevention is carried out. Strengths and weaknesses of approaches are identified to inform future development of MAW for SUDI prevention.

A key challenge in managing flow alteration is determining the severity and pattern of alteration associated with the degradation of biological communities. Understanding these patterns helps managers prioritize locations for restoration and flow management actions. However, the choices made about how to use these flow-ecology relationships can have profound implications on management decisions (e.g., which biological endpoints, which thresholds, which seasonal flow components to use). We describe a process for using flow-ecology relationships to prioritize management actions that 1) Represents the most relevant components of the annual hydrograph, 2) Demonstrates an appropriate level of sensitivity in order to discriminate locations to inform decision making, 3) Aims to protect multiple biological assemblages, 4) Reduces misclassification of priority areas (i.e., error of omission). Our approach is based on the functional flows approach which uses multiple flow metrics that describe the frequency, timing, magnitude, duration, and rate of change of seasonal process-based components of the annual hydrograph. Using this approach, we performed a flow-ecology analysis of regional bioassessment data, through which we determined where flow alteration impacts biology and prioritized reaches for changes in flow management to protect aquatic resources in a highly urbanized region of southern California, where managing scarce water resources leads to difficult decisions about tradeoffs that require technical information. We identified three important functional flow metrics for each of two bioassessment indices, one based on benthic macroinvertebrates, and another based on benthic algae. Based on thresholds that describe levels of alteration as well as thresholds describing the probability of achieving a healthy biological condition, we compared nine biological threshold combinations for each index. We found instances of flow alteration that impact biological condition highly variable (0–100% of subbasins) between combinations and we present a method for finding the most appropriate combination for prioritizing locations for flow management. We apply the final thresholds to the study region and propose 16 subbasins of high priority for implementing flow management and restoration. Importantly, we show that focusing on a single biological group would result in biologically altered locations being effectively ignored.

The basis for this study is to use students' creative texts in science as a mean to gain insight into their conceptual ideas. Eight grade students' creative writing tasks (n = 26) were analyzed with respect to the conceptual metaphors that were used to describe the abstract concept chemical bonding. The conceptual metaphors were identified and sorted into two main categories; location event-structure conceptual metaphors and object event-structure conceptual metaphors. Results show that most metaphors can be categorized as location event-structure conceptual metaphors. Embodied concepts and everyday language rooted in senso-motoric experiences from students’ daily life as well as from former science education seem to play a central role when they attempt to make meaning of the abstract concept ‘chemical bonding’ within a creative writing context. Creative writing tasks in science may have an unutilized potential for both uncovering and developing understanding of abstract phenomena on sub-microscopic level, such as chemical bonding.

This paper reports from a study where a teacher and researchers collaborated on designing science teaching promoting scientific inquiry for a group of students (age 11 – 13). Guided by the Norwegian science curriculum, students were during a two year intervention period regularly engaged in inquiry-based science learning. The students formed and tested hypotheses, were to various degrees engaged in developing research design and took extensively part in evaluation of evidence. In connection with each inquiry task, students were encouraged to express their ideas about professional or formal science emphasized in the Norwegian science curriculum (Why do scientists form and test hypothesis? What characterize scientific inquiry? Why do scientists compare results?). Data (video recordings of classroom instructions and interviews in addition to written tests) from four students were collected during a two year period. Results indicate that the students’ epistemological beliefs remained fairly naïve through the intervention period, in spite of intensive participation in inquiry learning. The students’ lack of epistemological development may be understood in terms of the instructional emphasis on formal epistemology, in favor of practical epistemology.

This paper reports from a study where a teacher and researchers collaborated on designing science teaching promoting scientific inquiry (processes of science) and science content (product of science) for a group of students (age 11 – 13). A wide range of data from students’ performance in combining science product and processes were collected during a two year period. Results indicate that students combined product (matter and change of matter) and processes of science (making hypotheses, suggesting research design and evaluating evidence) and that these aspects support each other in science learning. The ability of linking product and process differed among students and varied from one scientific method to the other. To succeed in linking science content and processes of science it is important to scaffold student understanding, like providing templates and asking rich and relevant questions.

Prosjektet ”Bedre læringsstrategier i realfag”, et samarbeidprosjekt mellom Nes kommune i Akershus og Høgskolen i Hedmark, startet som et skole-foreldreinitiativ for å oppnå bedre læringsresultater og utjevne sosiale forskjeller i Nes-skolen. Initiativet kom som følge av gjentatte nedslående resultater fra de internasjonale undersøkelsene PISA (OECD, 2003) og TIMSS (Grønmo, Bergem, Kjærnsli, Lie, & Turmo, 2004). Prestasjonene til norske elever i naturfag og matematikk er nå under det gjennomsnittlige OECD-resultatet (Kjærnsli, Lie, Olsen, & Roe, 2007). Tidligere har det blitt rapportert at elevene har et begrenset repertoar av læringsstrategier (Kjærnsli, Lie, Olsen, Roe, & Turmo, 2004; Lie, Kjærnsli, Roe, & Turmo, 2001). Som følge av funn i disse internasjonale undersøkelsene har begrepet læringsstrategier fått aktualitet og blitt løftet frem som en mulig vei til bedre læring (Elstad & Turmo, 2006). Den siste PISA-undersøkelsen (Kjærnsli et al., 2007) gir bare svak støtte til at bedre oppøving av gode læringsstrategier vil fremme elevenes læring i faget. Hvordan læringsstrategier tilpasset situasjoner og fag vil kunne fremme læring, er noe av det vi vil studere nærmere i dette prosjektet.

In this paper we suggest a method for analysing curriculums in science, and we use this to investigate how the present Norwegian science curriculum prepares students for scientific informed citizenry. Science is both a body of knowledge that represents current understanding of natural systems and the process where that body of knowledge has been established and is being continually extended, refined, and revised. Both elements are truly essential, a student cannot understand science without being competent in both. Thus, there are clear recommendations about how to teach science in school, described as four strands of learning. The method analyses competence descriptions both according to the four strands and taxonomic level (depth of knowledge). The analysis shows that the Norwegian curriculum only to a certain degree correlates to recommendations about how science should be taught. Moreover, it seems like the method has potential beyond science curriculum analysis.

I 2018 ble det lansert en ny strategi for kompetanseutvikling i skolen (Dekom). En viktig intensjon ved denne strategien var at lærere og ledere sammen med UH-sektoren skal utvikle kunnskap om undervisning og læring i de lokale skolekontekstene. I Storbynettverket ble det utviklet en modell for å ivareta intensjonen bak strategien, kalt ressursgruppemodellen. Målet med denne studien er å evaluere ressursgruppemodellen og identifisere hvilke faktorer som synes å være viktige for å lykkes i et storskala skoleutviklingsprosjekt. Det empiriske grunnlaget for studien er data fra spørreundersøkelser og fokusgruppeintervju med involverte parter fra skoler og UH- miljø. Deltakerne fikk spørsmål om erfaringene de hadde gjort seg etter første pulje med Dekom i Storbynettverket. Funnene viser blant annet at ressursgruppemodellen har en fleksibilitet som gjør at mange skoler kan delta parallelt samtidig som opplevde lokale behov kan ivaretas. Samtidig ser stabil ledelse, myndiggjøring av ressursgruppene og reelle samskapingsprosesser mellom UH og skolene ut til å være viktige faktorer for å lykkes med en slik storskala skoleutviklingsmodell. ENGLISH ABSTRACT Local Anchoring in Large-Scale School Development Projects – An Evaluation of a Model for Competence Development in which Many Schools Participate In 2018, a new strategy for competence development in schools (Dekom) was launched in Norway. An important intention of this strategy was for teachers and leaders, together with university employees, to develop knowledge about teaching and learning within local school contexts. In Storbynettverket, a model was developed to uphold the intention behind the strategy, called the resource group model. The aim of this study is to evaluate the resource group model and identify the factors that appear to be important for success in a large-scale school development project. The empirical basis for the study consists of data from surveys and focus group interviews with stakeholders from schools and universities. Participants were asked about their experiences after the first round of Dekom in Storbynettverket. Findings indicate that the resource group model has a flexibility that allows many schools to participate simultaneously while addressing perceived local needs. At the same time, stable leadership, empowerment of the resource groups, and genuine co-creation processes between higher education and schools seem to be important factors for success in a large-scale school development model.

Ifølge Kunnskapsløftet skal skolen bidra til å utvikle elevers skriveferdigheter fra skolestart. Tidligere forskning har imidlertid vist at lærere ikke opplever at lærerutdanningen forbereder dem i tilstrekkelig grad til å undervise i skriving på småtrinnet. Målet med denne studien var derfor å undersøke fra hvilke kunnskapskilder lærere på 1. trinn har utviklet sin kunnskap om skriveopplæring. Det empiriske grunnlaget for analysen var intervjuer med 116 lærere på 1. trinn ved 54 skoler. Lærerne fikk spørsmål om fra hvilke kunnskapskilder de har lært mest om skriving i begynneropplæringen. Materialet i studien var lydopptak og transkripsjoner fra intervjuene. Funnene viser blant annet at lærerne i hovedsak trekker fram kolleger, kurs/prosjekter og erfaring som kilder til kunnskap om skriveopplæring i begynneropplæringen, og at de i mindre grad trekker fram sin formelle utdanning. I artikkelen drøftes funnene og hvilke implikasjoner de kan ha for lærerutdanning og for andre som jobber med læreres læring når det kommer til skriveopplæring. ENGLISH ABSTRACT First-Grade Teachers’ Sources of Knowledge about Writing Instruction According to the Knowledge Promotion Reform, schools should contribute to developing students’ writing skills from the start of school. However, previous research has shown that teachers do not feel that teacher education prepares them sufficiently to teach writing in the early grades. Therefore, the goal of this study was to investigate from which sources of knowledge first-grade teachers have developed their knowledge about writing instruction. The empirical basis for the analysis was interviews with 116 first-grade teachers at 54 schools. The teachers were asked about the sources of knowledge from which they have learned the most about writing in beginner instruction. The material in the study consisted of audio recordings and transcriptions from the interviews. Findings suggest that the teachers primarily cite colleagues, courses/projects, and experience as sources of knowledge about writing instruction in elementary school and that they to a lesser degree refer to their formal education. The article discusses the findings and what implications they may have for teacher education and for others working with teacher learning when it comes to writing instruction.

Abstract The concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We develop murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicate IGLV3-21R110 expressing cell lines and primary CLL cells, but neither cells expressing the non-pathogenic IGLV3-21G110 light chain nor polyclonal healthy B cells. In vivo experiments confirm epitope-selective cytolysis in xenograft models in female mice using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for advanced approaches of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells.

BackgroundPeritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11–12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC.MethodsA first-in-human phase 1 study (EudraCT 2018–002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented.ResultsTwenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28–78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3–30). The peritoneal cancer index was median 7 (3–19), operation time was 395 min (194–515), and hospital stay was 12 days (7–37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution.ConclusionAll dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration:Clinicaltrials.gov, NCT 03732781.

I denne artikkelen tematiserer vi mottakerinstansen i skoleskriving, og hvordan denne realiseres i oppgaveformuleringer designet av lærere. Studien tar utgangspunkt i et oppgavemateriale fra Normprosjektet, hentet fra 3. – 7. trinn. I analysene kartlegger vi hvor tydelig mottakerinstansen kommer til uttrykk i oppgavene. Videre presenterer vi ulike kategorier mottakere og gir eksempler på disse. Blant annet ser vi på hvordan læreren er posisjonert som mottaker i skriveoppgavene, og drøfter den doble kommunikasjonssituasjonen som ligger i skolekonteksten. En av målsettingene er å studere oppgaver som er designet av lærere innenfor visse rammer i et forskningsprosjekt, og bruke funnene som utgangspunkt for mer generelle perspektiver. Vi ønsker med dette å igangsette en diskusjon i skriveforskningsmiljøet rundt forståelsen av begrepet autentisk skoleskriving og om hvem som skal være mottakere for elevers skriftlige tekster.

Forests play an important role in climate regulation due to carbon sequestration. However, a deeper understanding of forest carbon flux dynamics is often missing due to a lack of information about forest structure and species composition, especially for non-even-aged and species-mixed forests. In this study, we integrated field inventory data of a species-mixed deciduous forest in Germany into an individual-based forest model to investigate daily carbon fluxes and to examine the role of tree size and species composition for stand productivity. This approach enables to reproduce daily carbon fluxes derived from eddy covariance measurements (R2 of 0.82 for gross primary productivity and 0.77 for ecosystem respiration). While medium-sized trees (stem diameter 30–60 cm) account for the largest share (66%) of total productivity at the study site, small (0–30 cm) and large trees (>60 cm) contribute less with 8.3% and 25.5% respectively. Simulation experiments indicate that vertical stand structure and shading influence forest productivity more than species composition. Hence, it is important to incorporate small-scale information about forest stand structure into modelling studies to decrease uncertainties of carbon dynamic predictions.

The signal adapter MyD88, an essential component of Toll-like receptor (TLR) signaling, is important for gut-microbiome interactions. However, its contribution to cancer and its cell-type specific functions are controversially discussed. Therefore, we generated new tissue-specific mouse models and analyzed the clinical importance in human colorectal cancer. A gene-trap was inserted into the murine Myd88 gene (Myd88LSL), yielding MyD88-deficient background with Cre-mediated re-expression in myeloid (MYEL) or intestinal epithelial cells (IECs). These lines were bred with the Apc1638N model that develops invasive adenocarcinoma and analyzed at 12 months. Further, two patient collectives of colorectal cancer (n = 61, and n = 633) were analyzed for expression of Myd88 and TLRs. MyD88 expression was significantly increased in carcinomas, and increased intratumoral levels of MyD88 and TLR pathway components were associated with significantly shorter disease-free (P = .011), and overall survival (P < .0001). In accordance, fully MyD88-deficient mice showed highly significantly decreased tumor incidence, tumor numbers, increased survival, and, importantly, fully lacked malignant lesions. Thus, MyD88 is essential for tumorigenesis and especially progression to malignancy. Tissue-specific re-expression of MyD88 highly significantly increased tumor initiation by differing mechanisms. In intestinal epithelia, MyD88 enhanced epithelial turnover, whereas in myeloid cells, it led to increased production of tumor- and stemness-enhancing cytokines, significantly associated with altered expression of adaptive immune genes. However, neither re-expression of MyD88 in IECs or myeloid cells was sufficient for malignant progression to carcinoma. Thus, MyD88 crucially contributes to colorectal cancer initiation and progression with non-redundant and cell-type specific functions, constituting an attractive therapeutic target.