Päiväkodin johtajan ja varhaiskasvatuksen erityisopettajan jaettu asiantuntijuus laadukkaan pedagogiikan edistämisessä

Tiivistelmä. Tutkimuksen tavoitteena on tarkastella päiväkodin johtajien ja varhaiskasvatuksen erityisopettajien käsityksiä laadukkaasta pedagogiikasta ja sen kehittämiskohteista. Nykyinen varhaiskasvatuslaki (504/2018) ja Varhaiskasvatussuunnitelman perusteet (2018) säätelevinä asiakirjoina korostavat pedagogiikan merkitystä varhaiskasvatuksessa. Pedagogiikan painottuminen varhaiskasvatuksessa vaatii pedagogista asiantuntemusta ja pedagogisen toiminnan johtamistyötä varhaiskasvatukselle asetettujen tavoitteiden toteutumiseksi. Tarkastelemme tutkimuksessa myös, miten päiväkodin johtajat ja varhaiskasvatuksen erityisopettajat yhdessä toimien kehittävät ja ylläpitävät laadukasta pedagogiikkaa inklusiivisessa varhaiskasvatuksessa. Teoreettinen viitekehys kiinnittyy varhaiskasvatuksen laadun ja jaetun asiantuntijuuden näkökulmiin. Tarkastelun näkökulma on myös laadukkaassa pedagogiikassa. Tutkimuksemme on laadullinen tutkimus, joka toteutettiin fenomenografisen tutkimusotteen mukaisesti. Tutkimusaineisto on kerätty kahdella puolistrukturoidulla ryhmämuotoisella teemahaastattelulla. Haastattelut toteutettiin yhden kunnan alueelta haastattelemalla työpareina toimivia päiväkodin johtajia ja varhaiskasvatuksen erityisopettajia vuoden vaihteen 2019 ̶ 2020 aikana. Haastatteluaineisto nauhoitettiin, litteroitiin ja analysoitiin fenomenografisen tutkimusotteen keinoin. Haastatteluaineisto luokiteltiin aineistolähtöisen sisällönanalyysin mukaisesti. Tutkimus osoitti laadukkaan pedagogiikan kehittämistyön olevan jatkuva prosessi, jossa tärkeänä nähdään päiväkodin johtajan rooli ja hänen yhteistyönsä varhaiskasvatuksen erityisopettajan kanssa. Päiväkodin johtajat ja varhaiskasvatuksen erityisopettajat esittivät laadukkaan pedagogiikan toteutuvan Varhaiskasvatussuunnitelmien perusteiden mukaisena lasten yksilöllisyyden huomioivana toimintana, jonka perustana on pedagoginen johtaminen ja henkilöstön ammatillisuus. Henkilöstön varhaiskasvatussuunnitelmiin perustuvan ammattiosaamisen vahvistaminen nähtiin tutkimuksessa laadukkaan pedagogiikan kehittämiskohteena. Päiväkodin johtajan ja varhaiskasvatuksen erityisopettajan jaettu asiantuntijuus pedagogiikan johtamistyössä esitettiin laadukkaan pedagogiikan kehittämiskeinona. Tutkimuksen perusteella päiväkodin johtajan ja varhaiskasvatuksen erityisopettajan jaettu asiantuntijuus on kuitenkin vielä käyttämätön voimavara, jota voisi hyödyntää nykyistä enemmän pedagogiikan johtamistyössä laadukkaan pedagogiikan toteutumiseksi

Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes

OBJECTIVE: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years. RESULTS: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide. CONCLUSIONS: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide

Controlled induction of human pancreatic progenitors produces functional beta‐like cells in vitro

Directed differentiation of human pluripotent stem cells into functional insulin‐producing beta‐like cells holds great promise for cell replacement therapy for patients suffering from diabetes. This approach also offers the unique opportunity to study otherwise inaccessible aspects of human beta cell development and function in vitro. Here, we show that current pancreatic progenitor differentiation protocols promote precocious endocrine commitment, ultimately resulting in the generation of non‐functional polyhormonal cells. Omission of commonly used BMP inhibitors during pancreatic specification prevents precocious endocrine formation while treatment with retinoic acid followed by combined EGF/KGF efficiently generates both PDX1+ and subsequent PDX1+/NKX6.1+ pancreatic progenitor populations, respectively. Precise temporal activation of endocrine differentiation in PDX1+/NKX6.1+ progenitors produces glucose‐responsive beta‐like cells in vitro that exhibit key features of bona fide human beta cells, remain functional after short‐term transplantation, and reduce blood glucose levels in diabetic mice. Thus, our simplified and scalable system accurately recapitulates key steps of human pancreas development and provides a fast and reproducible supply of functional human beta‐like cells.SynopsisFocusing on developmental mechanisms, the results of this study further accelerate successful differentiation of human ESCs into functional pancreatic beta cells.Exclusion of commonly used BMP inhibitors during human embryonic stem cell to pancreatic progenitor differentiation prevents precocious endocrine induction.Sequential exposure of foregut cells to retinoic acid followed by combined EGF/KGF treatment establishes highly pure PDX1+ and PDX1+/NKX6.1+ progenitor populations, respectively.Precise temporal induction of endocrine differentiation in PDX1+/NKX6.1+ progenitors, but not in PDX1+/NKX6.1− progenitors, results in the generation of functional beta‐like cells in vitro.Beta‐like cells exhibit key features of bona fide human beta cells, remain functional after short‐term transplantation, and reduce blood glucose levels in diabetic mice.Focusing on developmental mechanisms, the results of this study further accelerate successful differentiation of human ESCs into functional pancreatic beta cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111932/1/embj201591058.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111932/2/embj201591058.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111932/3/embj201591058-sup-0001-FigsS1-S4.pd

Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from welldesigned clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population

An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

Peer reviewe

Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.Children’s Discovery InstituteMarch of Dimes Birth Defects FoundationNational Institute of General Medical Sciences (U.S.) (grant T32 GM081739)Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study)Sigrid Jusélius FoundationSigne and Anne Gyllenberg FoundationAcademy of FinlandVanderbilt University (Turner-Hazinski grant award

Mutant INS-Gene Induced Diabetes of Youth: Proinsulin Cysteine Residues Impose Dominant-Negative Inhibition on Wild-Type Proinsulin Transport

Recently, a syndrome of Mutant INS-gene-induced Diabetes of Youth (MIDY, derived from one of 26 distinct mutations) has been identified as a cause of insulin-deficient diabetes, resulting from expression of a misfolded mutant proinsulin protein in the endoplasmic reticulum (ER) of insulin-producing pancreatic beta cells. Genetic deletion of one, two, or even three alleles encoding insulin in mice does not necessarily lead to diabetes. Yet MIDY patients are INS-gene heterozygotes; inheritance of even one MIDY allele, causes diabetes. Although a favored explanation for the onset of diabetes is that insurmountable ER stress and ER stress response from the mutant proinsulin causes a net loss of beta cells, in this report we present three surprising and interlinked discoveries. First, in the presence of MIDY mutants, an increased fraction of wild-type proinsulin becomes recruited into nonnative disulfide-linked protein complexes. Second, regardless of whether MIDY mutations result in the loss, or creation, of an extra unpaired cysteine within proinsulin, Cys residues in the mutant protein are nevertheless essential in causing intracellular entrapment of co-expressed wild-type proinsulin, blocking insulin production. Third, while each of the MIDY mutants induces ER stress and ER stress response; ER stress and ER stress response alone appear insufficient to account for blockade of wild-type proinsulin. While there is general agreement that ultimately, as diabetes progresses, a significant loss of beta cell mass occurs, the early events described herein precede cell death and loss of beta cell mass. We conclude that the molecular pathogenesis of MIDY is initiated by perturbation of the disulfide-coupled folding pathway of wild-type proinsulin

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age

Abstract Background: Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective: The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods: The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results: Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P&lt;0.05, corrected for multiple comparison) in dorsolateral prefrontal caudate and ventrolateral prefrontal caudate tracts as compared to term-born children. We found negative correlations between the diffusion tensor imaging metrics of frontostriatal tracts and inhibition functions (P&lt;0.05, corrected for multiple comparison) in very preterm children. Conclusion: Prematurity has a long-term effect on frontostriatal white matter microstructure that might contribute to difficulties in executive functioning

Measuring higher-order cognitive skills with multiple choice questions:potentials and pitfalls of Finnish teacher education entrance

Abstract This mixed methods study examines the structure of the multiple-choice exam for student selection in Finnish teacher education. Through qualitative content analysis, we categorized multiple-choice questions into items that assessed lower- and higher-order cognitive processes based on the Revised Bloom’s Taxonomy. Exploratory and confirmatory factor analyses yielded four factors that represented lower- and higher-order cognitive processing skills and comprehension of empirical and theoretical items. These were associated with matriculation examination grades, especially with the average grade and the mother tongue grade. When developing future multiple-choice exams for admissions, we recommend emphasizing higher-order processing skills and the role of source materials