Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

INTRODUCTION Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. MATERIALS AND METHODS 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. RESULTS PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. CONCLUSION Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect

Financial difficulties among youth prenatally exposed to substances : a longitudinal register-based cohort study

Aim: The receipt of long-term financial social assistance (FSA) as an indicator of financial difficulties among Finnish youth with prenatal substance exposure (PSE) was investigated in comparison with unexposed youth. Methods: Data from national health and social welfare registers were collected for 18–24-year-old exposed (n = 355) and unexposed (n = 1011) youth. The influence of youth and maternal characteristics and out-of-home care (OHC) on the association between PSE and youth’s long-term FSA receipt was studied by generalized linear models and mediation analyses. Results: Exposed youth had an increased likelihood of long-term FSA receipt (OR 4.89, 95% CI 3.76, 6.37) but the difference with unexposed was attenuated following adjustments for youth and maternal characteristics and OHC (AOR 1.33, 95% CI 0.89, 1.98). Maternal long-term FSA receipt (0.48, 95% CI 0.35, 0.64) and OHC (0.63, 95% CI 0.47, 0.83) mediated a large proportion of the association between PSE and youth’s long-term FSA receipt. Youth’s mental or behavioral disorders partly mediated the association (0.21, 95% CI 0.14, 0.30), but the mediating effect of lack of secondary education was minor (0.03, 95% CI 0.01, 0.07). Conclusion: Receipt of long-term FSA among youth with PSE likely reflects maternal substance abuse linked with maternal financial situation and care instability in childhood.publishedVersionPeer reviewe

Frequencies of activated T cell populations increase in breast milk of HCMV-seropositive mothers during local HCMV reactivation

BackgroundHuman cytomegalovirus (HCMV) can reactivate in the mammary gland during lactation and is shed into breast milk of nearly every HCMV-IgG-seropositive mother of a preterm infant. Dynamics of breast milk leukocytes during lactation, as well as blood leukocytes and the comparison between both in the context of HCMV reactivation is not well understood.MethodsHere, we present the BlooMil study that aimed at comparing changes of immune cells in blood and breast milk from HCMV-seropositive- vs -seronegative mothers, collected at four time ranges up to two months post-partum. Viral load was monitored by qPCR and nested PCR. Multiparameter flow cytometry was used to identify leukocyte subsets.ResultsCD3+ T cell frequencies were found to increase rapidly in HCMV-seropositive mothers’ milk, while they remained unchanged in matched blood samples, and in both blood and breast milk of HCMV-seronegatives. The activation marker HLA-DR was more strongly expressed on CD4+ and CD8+ T cells in all breast milk samples than matched blood samples, but HCMV-seropositive mothers displayed a significant increase of HLA-DR+ CD4+ and HLA-DR+ CD8+ T cells during lactation. The CD4+/CD8+ T cell ratio was lower in breast milk of HCMV-seropositive mothers than in the blood. HCMV-specific CD8+ T cell frequencies (recognizing pp65 or IE1) were elevated in breast milk relative to blood, which might be due to clonal expansion of these cells during local HCMV reactivation. Breast milk contained very low frequencies of naïve T cells with no significant differences depending on serostatus.ConclusionTaken together, we conclude that the distribution of breast milk leukocyte populations is different from blood leukocytes and may contribute to the decrease of breast milk viral load in the late phase of HCMV reactivation in the mammary gland

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome

Objective CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy. Design Multicentre cohort study. Patients Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) ≥0.35 were treated with a single dose of CHF5633 within 48 hours after birth. The first 20 received 100 mg/kg and the second 20 received 200 mg/kg. Outcome measures Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue. Results Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100 mg/kg cohort and 53 AEs by 20 infants in the 200 mg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200 mg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected. Conclusions Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome: two-year outcomes

Objective: To assess at 24 months corrected age (CA) the neurological, respiratory, and general health status of children born prematurely from 27 +0 to 33 +6 weeks’ gestation who were treated in a first-in-human study with a new fully synthetic surfactant (CHF5633) enriched with SP-B and SP-C proteins.  Outcome measures: Children were assessed using Bayley Scales of Infant Development (BSID), with a score below normal defined as BSID-II Mental Development Index score <70, or BSID-III cognitive composite score <85. In addition, a health status questionnaire was used to check for functional disability including respiratory problems and related treatments, sensory and neurodevelopment assessments, communication skills as well as the number of hospitalizations.  Results: 35 of 39 survivors had a neurodevelopmental assessment, 24 infants being evaluated by Bayley’s Scales and 11 by health status questionnaires only. 23 children had scores within normal limits and one had BSID-III <85. The remaining 11 were judged clinically to have normal development. Health status questionnaires detected only issues that would normally be expected in preterm-born children.  Conclusions: This assessment offers reassurance that treatment with CHF5633 surfactant was not associated with adverse neurodevelopmental, respiratory, or health outcomes by two years corrected age

Att närma sig Afrika – hur man kan skapa en nyanserad bild i klassrummet

Sammanfattning Bilden som ges av Afrika i skolan och i media är inte så mångsidig som den kunde vara. Syftet med denna uppsats är att visa att man genom ämnesöverskridande projektarbete på ett samhällvetenskapligt program kan ge en nyanserad och rättvis bild av Afrika. Projektarbetet behandlar olika begrepp och delar i samråd med läraren trots att eleven ges stort eget ansvar där källkritisk analys ingår. Bedömningen av detta projektarbete sker bäst genom självreflektion samt muntlig framställning. Metoden för att nå detta svar har varit genom att studera litteratur och nyhetsartiklar i jämförelse med kursplanerna för de berörda ämnena; engelska, religion, historia, geografi, samhällskunskap och svenska. Material som använts för att nå resultatet är litteratur om afrikabilden, självreflektion och projektarbete som använts vid analys av de olika kursplanerna. Resultatet visar att det är möjligt att ge en nyanserad bild av Afrika genom ämnesöverskridande projektarbete eftersom elevernas olika uppfattningar om vad som är viktigt och riktigt kompletterar varandra och ökar lärandenivån. Genom att använda och utnyttja den enorma mängd information som idag enkelt finns att tillgå kan eleverna granska, jämföra och analysera material för att få fler svar på en fråga än de som ges i läroboken. För läraryrket är detta viktigt eftersom man som lärare har ett stort ansvar att förmedla sanningen. Att lärare får arbeta ämnesöverskridande är även utvecklande, nyttigt och kanske roligt även för dem. Att få del av andra lärares arbete och andra ämnens kursmål är bara positivt för att skapa ett samband även för lärarnas arbete och egna ämnen

THE INTERACTIVE ICONS OF THE INTERFACE : Better User Understanding Through Graphical Design

Det här arbetet undersöker hur klickbara ikoner i spel grafiskt borde utformas för att mest effektivt kommunicera sin funktion till spelaren. De riktlinjer som används för detta utgår främst från forskning kring människors interaktion med datorer och kognitiv perception. Arbetets problemformulering frågade sig om användandet av mänskliga figurer, som en del av ikonutformningen, kan hjälpa detta kommunicerande. För att testa detta togs två versioner av fyra olika ikonerna fram, en med mänskliga komplement och en utan. Ikonerna utformades till ett lärospel för Balthazar Science Center, vilket utvecklades i samband med denna undersökning. Frågeställningen testades genom intervjuer med elva- till tolvåringar, alltså spelets målgrupp, vilka fick gissa ikonernas funktion utifrån den grafiska utformningen. Resultatet visade på att de mänskliga komplementen inte gav någon märkbar fördel för ikonutformningen, och att ikonförståelsen i stor grad berodde på respondenternas tidigare spelvana. Detta arbete förslår bland annat att fortsatta studier kan genomföras inom andra spelgenre

Teacher perspectives on formative feedback : A qualitative study on how teachers in digital aesthetic subjects think feedback should be designed to enchance student engagement, motivation and learning.

En studie i hur lärare i digitala estetisk-praktiska ämnen upplever att feedback ökar elevernas engagemang, motivation och kunskapsutveckling. Denna studie undersöker lärares perspektiv på formativ feedback som en aktiv del i att möjliggöra kunskapsutveckling i digitala praktiskt estetiska kurser. Studien vill hitta praktiska konkreta exempel på vad som kännetecknar en god formativ feedback. Avgränsningen till digitala kreativa kurser som webbutveckling, digitalt skapande, medieproduktion med mera, är för att få lärarnas perspektiv på hur feedback lyfter elevernas motivation utan att minska deras kreativitet i skapandet till exempel att designa en webbsida. Studien är en kvalitativ studie byggd på semistrukturerade intervjuer med fem respondenter. Resultatet visar att det finns några nyckelfaktorer för framgångsrik framåtsyftande formativ feedback. De viktigaste är relationen mellan lärare och elev, god kännedom om elevens kunskapsnivå, tydlighet i lärarens feedback som bör vara muntlig för att kunna bemötas eller förtydligas samt att tajmingen är viktig, ingen feedback för tidigt i projekt och gärna i slutet av ett moment. Utmaningar i att ge framgångsrik feedback är främst avvägningen att inte styra för mycket eller ge lösningar samt att vissa elever inte tar till sig feedback