The relationship between organizational culture and the implementation of response to intervention in one elementary school

This study investigated the relationship between organizational culture and the implementation of Response to Intervention in one elementary school. It examined issues corresponding to change within a system, with particular attention to those relating to school culture. An ethnographic approach was used to gather data, including the collection of artifacts, observations, and interviews. This study found that the implementation of RTI presents numerous organizational, school culture, and leadership challenges. At the organizational level, RTI affects the entire district by changing the instructional focus to include early intervening services and the process by which students are found eligible for special education. This impacts multiple aspects of the school: scheduling, the use of instructional staff, student placement in classes, budget issues, and professional development for staff. These organizational issues present a significant challenge for a district facing a serious financial crisis. School culture plays a significant role in what is valued by the organization. Schools are a collection of individuals and their relationships with others. It is through these relationships and shared understanding that school culture is preserved. The school culture at Newberry is one of collaboration and teamwork; the irrelationships and shared values led to the successful implementation of RTI. Schools are a microcosm of the community. While schools share numerous elements, each school culture is unique. To understand a group of people, it is important to understand the contextual elements that influence individual and institutional behaviors (Schein, 1992). The village of Newberry has a unique history of rugged pioneerism and an interdependent relationship with state institutions that has influenced the school culture. The staff was able to recognize the cultural and economic benefits of state institutions and their influence on the make-up of the community and school population, which resulted in a school climate conducive to implementing RTI. This study found that school leadership plays a significant role in the implementation of RTI. Newmann (1996) found that in the majority of schools studied, the school’s ability to sustain new practices was largely dependent on the principal’s leadership. This study found that one reason the staff at Newberry was able to successfully implement RT I was the support and leadership from the school administration

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium ( www.cebiond.org ), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field

Reading Poetry and Prose: Eye Movements and Acoustic Evidence

We examined genre-specific reading strategies for literary texts and hypothesized that text categorization (literary prose vs. poetry) modulates both how readers gather information from a text (eye movements) and how they realize its phonetic surface form (speech production). We recorded eye movements and speech while college students (N = 32) orally read identical texts that we categorized and formatted as either literary prose or poetry. We further varied the text position of critical regions (text-initial vs. text-medial) to compare how identical information is read and articulated with and without context; this allowed us to assess whether genre-specific reading strategies make differential use of identical context information. We observed genre-dependent differences in reading and speaking tempo that reflected several aspects of reading and articulation. Analyses of regions of interests revealed that word-skipping increased particularly while readers progressed through the texts in the prose condition; speech rhythm was more pronounced in the poetry condition irrespective of the text position. Our results characterize strategic poetry and prose reading, indicate that adjustments of reading behavior partly reflect differences in phonetic surface form, and shed light onto the dynamics of genre-specific literary reading. They generally support a theory of literary comprehension that assumes distinct literary processing modes and incorporates text categorization as an initial processing step

A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury.

Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted--ischemia--and then restored--reperfusion--leading to a burst of reactive oxygen species (ROS) from mitochondria. It has been tacitly assumed that ROS production during IR is a non-specific consequence of oxygen interacting with dysfunctional mitochondria upon reperfusion. Recently, this view has changed, suggesting that ROS production during IR occurs by a defined mechanism. Here we survey the metabolic factors underlying IR injury and propose a unifying mechanism for its causes that makes sense of the huge amount of disparate data in this area and provides testable hypotheses and new directions for therapies.Work in our laboratories is supported by the Medical Research Council (UK) and the British Heart Foundation. E.T.C. is supported by a Human Frontiers Science Program fellowship.This is the author accepted manuscript. The final version is available from Cell Press via http://dx.doi.org/10.1016/j.cmet.2015.12.00

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10(-5)). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation

Miocene (23–13 Ma) continental paleotemperature record from the northern Mediterranean region (Digne-Valensole Basin, SE France) within a global climatic framework

During the Middle Miocene, the Earth’s climate transitioned from a warm phase, the Miocene Climatic Optimum (MCO, 16.9–14.7 Ma), to a colder phase associated by formation of major ice sheets on Antarctica. This climatic shift, the Middle Miocene Climatic Transition (MMCT, 14.7–13.8 Ma), considerably impacted not only the structure and formation of major ecosystems (e.g. Jimenez-Moreno & Suc, 2005) it also affected global ocean circulation (Holbourn et al., 2014), terrestrial temperatures as well as precipitation patterns (e.g. Methner et al., 2020). While the MCO and the subsequent MMCT are well described in marine records, knowledge about the magnitude and rate of terrestrial paleoclimate changes is often limited by lack of temporal resolution and reliable quantitative proxy records (Steinthorsdottir et al., 2021). Here, we present a long-term (23–13 Ma) biostratigraphically-controlled terrestrial stable (δ18O, δ13C) and clumped (Δ47) isotope paleosol carbonate record from the northern Mediterranean region (Digne-Valensole basin, SE France). When comparing the northern Mediterranean δ18O, δ13C and Δ47 record with age-equivalent counterparts from central Europe (Northern Alpine Foreland Basin, Switzerland), our Δ47 results from the Digne-Valensole basin reveal two important features: 1) Relatively warm and constant carbonate formation temperatures (ca. 30°C) for the Early Miocene (23–18.6 Ma) followed by 2) intensified temperature fluctuations with high values (ca. 37°C) at the onset of the MCO, most probably amplified by changes in seasonality of pedogenic carbonate formation. The combined Northern Alpine foreland and northern Mediterranean records display a coherent climate pattern for the Middle Miocene circum-Alpine foreland. In both records, high-amplitude, rapid changes in Δ47 temperatures (ca. 18°C within 400 ka) characterize the onset of the MCO and MMCT. We furthermore identify warm peaks during the MCO and a distinct fall in apparent Δ47-based temperatures at ca. 14 Ma that is in very good temporal agreement with oceanic isotope records and coincides with the documented global cooling following the MCT. Collectively, these data contribute to understanding of the dynamics and variability in atmospheric circulation controlling Middle to Late Miocene temperature dynamics in the Northern Mediterranean region

Expression of Rb2/p130 in breast and endometrial cancer: correlations with hormone receptor status

Rb2/p130 is a member of the retinoblastoma family of proteins, consisting of Rb, Rb2 and p107, which are important negative regulators of cell cycle progression and differentiation. While Rb2 downregulation was observed in several malignant tumours including endometrial cancer, the role of p130 in breast carcinomas is still unknown. We investigated Rb2 protein expression in tumour tissue from 68 mammary and 41 endometrial carcinomas, 4 mammary cell lines, and normal tissue samples. Therefore, we performed Western blot experiments for Rb2, Rb, and the oestrogen and progesterone receptors (ER, PR-A, PR-B). Weak or absent Rb2 expression was more often found in endometrial (59%) than in mammary carcinomas (24%). We found significant positive correlations of Rb2 expression with Rb, ER, and PR-B in breast cancer samples, and of Rb2 with Rb, PR-A, PR-B, and younger age in endometrial carcinomas. No significant associations with histological grading, stage, nodal involvement, or Ki67 staining were detected. Rb2 mRNA expression was studied by semi-quantitative RT-PCR in 56 endometrial or mammary tissue samples and correlated significantly with Western blot results. Our results indicate that loss of Rb2 expression, mostly by transcriptional down-regulation, may be associated with the development and dedifferentiation of most endometrial and a subset of mammary carcinomas. © 2001 Cancer Research Campaign http://bjcancer.co