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In recent years, education policy scholars have begun to utilize social network concepts and methods to describe contemporary policy changes across P-16 levels. While many insights have emerged from this growing literature base, we argue that a more formal network approach rooted in policy network analysis (PNA) is needed to fulfill its conceptual and analytical ambitions. Policy network analysis integrates concepts from social network analysis with theoretical assumptions developed in the field of political science. Toward this end, we first argue that a more rigorous treatment of policy beliefs is needed to analyze the impact of ideas on the policy agenda. Existing literature on the ideological dimensions of market-based reform movements tends to define them largely within the bounds of neo-liberalism and thus far has failed to systematically explain how policy beliefs emerge and converge in this context. Second, we contend that previous work has generally lacked theoretical grounding in formal policy network analysis (PNA). Although there are clear links between the concepts and findings in traditional PNA literature and educational research – particularly the use of networked governance as a concept for understanding the interconnectedness of educational reform networks – a more diligent application of PNA theory and methods would enable educational policy scholars to gain deeper insights into the explanatory processes of policy change. We pay particular attention to the usefulness of these approaches for examining two-mode network data and for modeling ideological policy change.

This preprint is a 1000-word Viewpoint that explores methodological considerations of the COVID-19 pandemic for immunopsychiatry. It has been accepted for publication in Brain, Behavior, and Immunity for a special issue on Immunopsychiatry and COVID-19. Specifically, we discuss the treatment of COVID-19 as a confounding versus mediating variable in immunopsychiatric research. We leverage simulated data varied in sample and effect size to illustrate key considerations. Further, we highlight the statistical implications of each of these scenarios. Recommendations and key considerations for the field are briefly discussed.

Cerebral atrophy is a common finding in elderly patients; however, cerebrovascular disease causing progressive focal cerebral atrophy and dysfunction is unusual. In this report, we present 3 cases of hemicerebral atrophy due to ipsilateral internal carotid artery (ICA) stenosis or occlusion mimicking neurodegenerative conditions. Patient 1 had a frontal dysexecutive syndrome potentially consistent with a diagnosis of behavioral variant frontotemporal dementia; however, neuroimaging revealed a chronically occluded left ICA and a pattern of atrophy restricted to the left middle cerebral artery territory, suggestive of a vascular etiology. Patient 2 presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction, with radiographic evidence of left hemicerebral atrophy. Angiography revealed a chronic dissection of the left ICA leading to left cerebral hypoperfusion. Patient 3 had asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of corticobasal syndrome. His imaging, however, revealed atrophy and encephalomalacia within the anterior circulation watershed territories with chronic, severe stenosis of the left ICA suggestive of a chronic hypoperfused state. In this case series, we report 3 examples of hemicerebral atrophy secondary to chronic ipsilateral ICA vascular disease with diverse progressive clinical symptoms mimicking primary neurodegenerative conditions. This case series highlights the importance of considering chronic hypoperfusion and large-vessel severe stenosis or occlusion in patients with cognitive impairment and evidence of asymmetric brain atrophy. In addition to symptomatic treatment, the management of vascular risk factors including treatment with antiplatelet agents, statins, and revascularization procedures can be considered.

The total cost of Parkinson disease (PD), which affects nearly 1 million people in the US is $52 billion every year, with $25.4 billion attributable to direct medical costs such as hospitalizations and medication, and $26.5 billion in non-medical costs like missed work, lost wages, early forced retirement, and family caregiver time. The more we know about PD’s non-motor symptoms—depression, dementia, fatigue, and others—the better we can treat, and perhaps find a cure, for this neurological disorder.

Rund einhundert Nachwuchswissenschaftler_innen trafen sich vom 13.–15. Februar 2018 an der Ruhr-Universität Bochum zum 31. Film- und Fernsehwissenschaftlichen Kolloquium (FFK). Die vierte Ausgabe des ffk Journals bringt in zwanzig ausgewählten Beiträgen einen repräsentativen Teil der dort vorgestellten, diskutierten und reflektierten medien-, film- und fernsehwissenschaftlichen Forschung zur Dokumentation.

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses.

Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.

Type I interferon (IFN-α/β) plays a critical role in suppressing viral replication by driving the transcription of hundreds of interferon-sensitive genes (ISGs). While many ISGs are transcriptionally activated by the ISGF3 complex, the significance of other signaling intermediates in IFN-α/β-mediated gene regulation remains elusive, particularly in rare cases of gene silencing. In human Th2 cells, IFN-α/β signaling suppressed IL5 and IL13 mRNA expression during recall responses to T-cell receptor (TCR) activation. This suppression occurred through a rapid reduction in the rate of nascent transcription, independent of de novo expression of ISGs. Further, IFN-α/β-mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN-α/β signaling and highlights the unique activity of this cytokine to acutely block the expression of an inflammatory cytokine in human T cells.

The focus of this thesis is the discoloration of a common historical green pigment, copper resinate. In this research the discoloration was investigated in Jacopo Tintoretto’s painting, Allegorical Figure of Spring, painted c. 1555. This painting is believed to have been painted with copper resinate which has discolored to brown over the centuries. The state of repair of the painting was determined using visual analysis under visible and UV light and the use of copper green pigments was confirmed using energy-dispersive X-ray fluorescence, including copper resinate based upon supplementary historical evidence. Substantial evidence was found from visual inspection and XRF determination of pigments that the painting had originally been lozenge-shaped and had been given its current rectangular shape only after the addition of supplementary canvas to its corners and top and bottom. Inspection of the painting under UV light highlighted areas of damage and repair, and the appearance of modern pigments such as titanium white and zinc white indicated that repairs and overpainting had been conducted as recently as the twentieth century. I also conducted an investigation of copper resinate in the laboratory to determine its chemical composition, stability and possible modes of degradation. For my study of copper resinate, I used pigments synthesized by historic and modern recipes to determine its composition using mass spectrometry and FTIR. I determined that in either case copper resinate is a mixture of copper compounds containing acetate and abietate ligands in varying ratios including [Cu2Ab4], [Cu2Ab3Ac], and [Cu2Ab2Ac2]. I investigated its chemical properties and stability by extraction, UV absorption, subjection to various solvents and environments. I found that the green color of copper resinate is a result of a combination of blue copper carboxylate compounds and free abietic acid, which is yellow in color. I also found that the drying process of copper resinate is light- and water-dependent and that both verdigris and copper resinate quickly discolor to brown upon the addition of a dilute basic solution. From this evidence, I hypothesize that the discoloration of copper resinate results from exposure to water in the environment and traditional treatments leading to the slow degradation of the pigment to brown copper oxide.

Research on ecosystem resilience and climate–ecosystem interactions is extremely complex due to the large variety of factors that play a role in ecosystem functioning. This study aimes at determining which factors are involved in ecosystem resilience, which methods are needed to investigate this, and how archaeology can contribute to such research. The influence of the 8.2 ka climate event on the natural environment of Tell Sabi Abyad, Syria, serves as a case study for larger-scale ecosystem resilience studies. This study presents some critical notes to the assumption that the changes which took place in Tell Sabi Abyad at the timing of the 8.2 ka event were a direct result of climate change triggered by the event. Though a number of changes in culture and farming methods date back to the timing of the 8.2 ka event, as yet no evidence has been found for wild flora and fauna shifts which could indicate climate deterioration. Other factors that could have influenced the changes observed in the archaeological record, like anthropogenic influences or cultural development, should not be ruled out as determining factors for the changes that took place at Tell Sabi Abyad at the timing of the 8.2 ka event.

CD4+ T helper type 2 (Th2) development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive feedback loop that maintains elevated GATA3 expression. Type I interferon (IFN-α/β) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed Th2 cells. In this study, we have uncovered a unique mechanism by which IFN-α/β signaling represses the GATA3 gene in human Th2 cells. IFN-α/β suppressed expression of GATA3 mRNA that was transcribed from an alternative distal upstream exon (1A). This suppression was not mediated through DNA methylation, but rather by histone modifications localized to a conserved non-coding sequence (CNS-1) upstream of exon 1A. IFN-α/β treatment lead to a closed conformation of CNS-1 as assessed by DNase I hypersensitivity along with enhanced accumulation of H3K27me3 mark at this CNS region, which correlated with increased density of total nucleosomes at this putative enhancer. Consequently, accessibility of CNS-1 to GATA3 DNA binding activity was reduced in response to IFN-α/β signaling, even in the presence of IL-4. Thus, IFN-α/β disrupts the GATA3 autoactivation loop and promotes epigenetic silencing of a Th2-specific regulatory region within the GATA3 gene.

Background Pregnant women in Canada have traditionally received prenatal care individually from their physicians, with some women attending prenatal education classes. Group prenatal care is a departure from these practices providing a forum for women to experience medical care and child birth education simultaneously and in a group setting. Although other qualitative studies have described the experience of group prenatal care, this is the first which sought to understand the central meaning or core of the experience. The purpose of this study was to understand the central meaning of the experience of group prenatal care for women who participated in CenteringPregnancy through a maternity clinic in Calgary, Canada. Methods The study used a phenomenological approach. Twelve women participated postpartum in a one-on-one interview and/or a group validation session between June 2009 and July 2010. Results Six themes emerged: (1) "getting more in one place at one time"; (2) "feeling supported"; (3) "learning and gaining meaningful information"; (4) "not feeling alone in the experience"; (5) "connecting"; and (6) "actively participating and taking on ownership of care". These themes contributed to the core phenomenon of women "getting more than they realized they needed". The active sharing among those in the group allowed women to have both their known and subconscious needs met. Conclusions Women's experience of group prenatal care reflected strong elements of social support in that women had different types of needs met and felt supported. The findings also broadened the understanding of some aspects of social support beyond current theories. In a contemporary North American society, the results of this study indicate that women gain from group prenatal care in terms of empowerment, efficiency, social support and education in ways not routinely available through individual care. This model of care could play a key role in addressing women's needs and improving health outcomes.

Mitochondria form an interconnected network that undergoes dynamin-related protein 1 (Drp1)-dependent fission during mitosis. We demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven through ubiquitylation of Drp1 by the (anaphase- promoting complex/cyclosome and its coactivator Cdh1) APC/CCdh1 complex. Inhibition Drp1 degradation prevents the normal regrowth of mitochondrial networks during G1 phase.Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/CCdh1 (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division.