448 research outputs found
Addressing the 'leadership conundrum' through a mixed methods study of school leadership for literacy
This paper explores methodological insights from a mixed methods study that aims to understand how school leaders promote literacy development in their schools. The study findings consider both the complementarities and the challenges of the qualitative and quantitative approaches to measuring leadership practices and their linkages with learning across schools. We begin by identifying a conundrum in school leadership and management (SLM) research â strong effects found in qualitative studies and weaker effects in quantitative studies. From the literature we identify some of the central challenges that account for these differences. We then show how these challenges were and were not addressed in the mixed method research we conducted in an SLM study of South African primary schools in challenging contexts. We consider why the central aim of the study â to develop a scalable instrument for measuring SLM â remains elusive
Colony organization in the green alga Botryococcus braunii (Race B) is specified by a complex extracellular matrix
Botryococcus braunii is a colonial green alga whose cells associate via a complex extracellular matrix (ECM) and produce prodigious amounts of liquid hydrocarbons that can be readily converted into conventional combustion engine fuels. We used quick-freeze deep-etch electron microscopy and biochemical/histochemical analysis to elucidate many new features of B. braunii cell/colony organization and composition. Intracellular lipid bodies associate with the chloroplast and endoplasmic reticulum (ER) but show no evidence of being secreted. The ER displays striking fenestrations and forms a continuous subcortical system in direct contact with the cell membrane. The ECM has three distinct components. (i) Each cell is surrounded by a fibrous ÎČ-1, 4- and/or ÎČ-1, 3-glucan-containing cell wall. (ii) The intracolonial ECM space is filled with a cross-linked hydrocarbon network permeated with liquid hydrocarbons. (iii) Colonies are enclosed in a retaining wall festooned with a fibrillar sheath dominated by arabinose-galactose polysaccharides, which sequesters ECM liquid hydrocarbons. Each cell apex associates with the retaining wall and contributes to its synthesis. Retaining-wall domains also form âdrapesâ between cells, with some folding in on themselves and penetrating the hydrocarbon interior of a mother colony, partitioning it into daughter colonies. We propose that retaining-wall components are synthesized in the apical Golgi apparatus, delivered to apical ER fenestrations, and assembled on the surfaces of apical cell walls, where a proteinaceous granular layer apparently participates in fibril morphogenesis. We further propose that hydrocarbons are produced by the nonapical ER, directly delivered to the contiguous cell membrane, and pass across the nonapical cell wall into the hydrocarbon-based ECM
Quality of life in lung cancer survivors treated with tyrosine-kinase inhibitors (TKI) : results from the multi-centre cross-sectional German study LARIS
Purpose We aimed at exploring the quality of life (QOL) of lung cancer survivors with proven tyrosine-kinase receptor
(RTK) genetic alterations and targeted tyrosine-kinase inhibitors (TKI) therapy, compared to lung cancer survivors with
no-RTK alterations and no-TKI therapy.
Methods Data were collected in a cross-sectional multi-centre study. Primary lung cancer survivors were asked about their
socio-demographic and clinical information, QOL, symptom burden, and distress. QOL and symptom burden were assessed
using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC
QLQ-C30), and distress with the Patient Health Questionnaire-4 (PHQ-4). Demographic and clinical characteristics were
reported in absolute and relative frequencies, QOL, and symptom burden using mean scores. Diferences in mean scores
with relative 95% confdence intervals were used for comparison.
Results Three groups of survivors were defned: group A with proven RTK alterations, TKI therapy at any time during
therapy, and stage IV lung cancer at diagnosis (n=49); group B: non-TKI therapy and stage IV lung cancer (n=121);
group C: non-TKI therapy and stage IâIII lung cancer (n=495). Survivors in group A reported lower QOL (mean score
diference=-11.7 vs. group B) and symptom burden for dyspnoea (diference=-11.5 vs. group C), and higher symptom
burden for appetite loss (diference= +11.4 vs. group C), diarrhoea and rash (diferences= +25.6,+19.6 and+13.2,+13.0,
respectively, vs. both groups).
Conclusions Our results suggest that the specifc side efects of TKI therapy can impair QOL among lung cancer survivors.
Therefore, specifc focus towards the optimal management of these side efects should be considered
Transient shoaling, over-deepening and settling of the calcite compensation depth at the Eocene-Oligocene transition
The path to triacylglyceride obesity in the sta6 strain of Chlamydomonas reinhardtii
When the sta6 (starch-null) strain of the green microalga Chlamydomonas reinhardtii is nitrogen starved in acetate and then âboostedâ after 2 days with additional acetate, the cells become âobeseâ after 8 days, with triacylglyceride (TAG)-filled lipid bodies filling their cytoplasm and chloroplasts. To assess the transcriptional correlates of this response, the sta6 strain and the starch-forming cw15 strain were subjected to RNA-Seq analysis during the 2 days prior and 2 days after the boost, and the data were compared with published reports using other strains and growth conditions. During the 2 h after the boost, âŒ425 genes are upregulated â„2-fold and âŒ875 genes are downregulated â„2-fold in each strain. Expression of a small subset of âsensitiveâ genes, encoding enzymes involved in the glyoxylate and Calvin-Benson cycles, gluconeogenesis, and the pentose phosphate pathway, is responsive to culture conditions and genetic background as well as to boosting. Four genesâencoding a diacylglycerol acyltransferase (DGTT2), a glycerol-3-P dehydrogenase (GPD3), and two candidate lipases (Cre03.g155250 and Cre17.g735600)âare selectively upregulated in the sta6 strain. Although the bulk rate of acetate depletion from the medium is not boost enhanced, three candidate acetate permease-encoding genes in the GPR1/FUN34/YaaH superfamily are boost upregulated, and 13 of the âsensitiveâ genes are strongly responsive to the cell's acetate status. A cohort of 64 autophagy-related genes is downregulated by the boost. Our results indicate that the boost serves both to avert an autophagy program and to prolong the operation of key pathways that shuttle carbon from acetate into storage lipid, the combined outcome being enhanced TAG accumulation, notably in the sta6 strain
Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery : Combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds
Objectives: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDASâ€2.6), low (LDAS>2.6-3.2), low-moderate (LMDASâ„3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). Results: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.Peer reviewedFinal Published versio
Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface
Plasma concentrations of biologically active vitamin D (1,25-
(OH)2D) are tightly controlled via feedback regulation of renal
1-hydroxylase (CYP27B1; positive) and 24-hydroxylase
(CYP24A1; catabolic) enzymes. In pregnancy, this regulation is
uncoupled, and 1,25-(OH)2D levels are significantly elevated,
suggesting a role in pregnancy progression. Epigenetic regulation
of CYP27B1 and CYP24A1 has previously been described in
cell and animal models, and despite emerging evidence for a
critical role of epigenetics in placentation generally, little is
known about the regulation of enzymes modulating vitamin D
homeostasis at the fetomaternal interface. In this study, we
investigated the methylation status of genes regulating vitamin
D bioavailability and activity in the placenta. No methylation of
the VDR (vitamin D receptor) and CYP27B1 genes was found in
any placental tissues. In contrast, the CYP24A1 gene is methylated
in human placenta, purified cytotrophoblasts, and primary
and cultured chorionic villus sampling tissue. No methylation
was detected in any somatic human tissue tested. Methylation
was also evident in marmoset and mouse placental tissue. All
three genes were hypermethylated in choriocarcinoma cell
lines, highlighting the role of vitaminDderegulation in this cancer.
Gene expression analysis confirmed a reduced capacity for
CYP24A1 induction with promoter methylation in primary cells
and in vitro reporter analysis demonstrated that promoter
methylation directly down-regulates basal promoter activity
and abolishes vitamin D-mediated feedback activation. This
study strongly suggests that epigenetic decoupling of vitamin D
feedback catabolism plays an important role in maximizing
active vitamin D bioavailability at the fetomaternal interface
Mutuality as a method: advancing a social paradigm for global mental health through mutual learning
Purpose:
Calls for âmutualityâ in global mental health (GMH) aim to produce knowledge more equitably across epistemic and power differences. With funding, convening, and publishing power still concentrated in institutions in the global North, efforts to decolonize GMH emphasize the need for mutual learning instead of unidirectional knowledge transfers. This article reflects on mutuality as a concept and practice that engenders sustainable relations, conceptual innovation, and queries how epistemic power can be shared.
//
Methods:
We draw on insights from an online mutual learning process over 8 months between 39 community-based and academic collaborators working in 24 countries. They came together to advance the shift towards a social paradigm in GMH.
//
Results:
Our theorization of mutuality emphasizes that the processes and outcomes of knowledge production are inextricable. Mutual learning required an open-ended, iterative, and slower paced process that prioritized trust and remained responsive to all collaboratorsâ needs and critiques. This resulted in a social paradigm that calls for GMH to (1) move from a deficit to a strength-based view of community mental health, (2) include local and experiential knowledge in scaling processes, (3) direct funding to community organizations, and (4) challenge concepts, such as trauma and resilience, through the lens of lived experience of communities in the global South.
//
Conclusion:
Under the current institutional arrangements in GMH, mutuality can only be imperfectly achieved. We present key ingredients of our partial success at mutual learning and conclude that challenging existing structural constraints is crucial to prevent a tokenistic use of the concept
Measured energy content of frequently purchased restaurant meals : multi-country cross sectional study
Funding: This work was supported in part by the US Department of Agriculture under agreement no. 58-1950-4-003 with Tufts University and a Tufts University Provost award to SBR. The study had additional funding in Brazil from FAPESP grants 2013/18520-0 and 2013/14489-1 to VS; in China from the National Science Foundation of China grant No 91431102 to JRS and International Partnership Program of Chinese Academy of Sciences grant No GJHZ1660 to JRS; in Finland from internal funding by the University of Eastern Finland to JP; in Ghana from the University of Georgia Global Research Collaborative Grant Program to AKA. The views expressed are those of the authors. The sponsors had no role in the design, undertaking, or reporting of the study.Peer reviewedPublisher PD
- âŠ