1,174 research outputs found

    A survey of the impact of summer droughts in southern and eastern England, 1200-1700

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    Droughts pose a climatic hazard that had profound impacts on past societies. Using documentary sources, this paper studies the occurrence and impacts of spring-summer droughts in pre-industrial England from 1200 to 1700. The types of records, source availability and changes in record keeping over time are described, and an overview of droughts in those 500 years is provided. The focus lies on a structural survey over the drought impacts most relevant to human livelihood. This includes the agricultural and pastoral sectors of agrarian production, health, the fire risk to settlements, and the drop in water levels or dwindling of water supplies. Due to the specific characteristics of wheat cultivation in medieval and early modern England, the grain production was comparatively resilient to drought, whereas livestock farming was under threat when rainfall fell noticeably below average. Nonetheless, the most important problem in warm and dry summers was the risk to health. Partly steeply raised mortality levels were associated with these conditions during the study period because malaria, gastrointestinal disease and plague showed an affinity to heat and drought. Adaptation strategies to reduce the stress posed by summer droughts are included in the study

    Genomic Instability and the Oncohistone H3K27M Drive Gliomagenesis in a Murine Model

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    Maintaining genome stability is crucial for human health and it is of particular importance in neural cells during early brain development. Genome maintenance occurs at two broad stages; surveillance during DNA replication and DNA damage repair in differentiating and mature cells. Neural cells are particularly sensitive to DNA strand breaks and defective DNA damage responses can result in detrimental effects on the nervous system, including cancer. Multiple DNA repair pathways play critical roles in preventing DNA damage accumulation in stem and neural progenitor cells. The mechanisms that protect progenitor genomes also suppress DNA mutations that can result in cancer. A primary objective of this dissertation is to understand the relative contributions of key DNA repair factors that prevent tumorigenesis during cortical development. We have compared the differential effects of inhibition of homologous recombination (HR), via BRCA2-inactivation and non-homologous end-joining (NHEJ), via LIG4-inactivation towards tumorigenesis by directing their deletion specifically to early cortical progenitors using an Emx1-cre recombinase driver. We find that coincident loss of either of these repair pathways with p53 inhibition result in distinct high-grade glioma (HGG) formation resulting from elevated genome instability by DNA damage accumulation during embryogenesis. Furthermore, the presence of the oncohistone H3K27M mutation, commonly found in pediatric HGGs, enhances genome instability and accelerates cortical gliomagenesis with p53 inactivation and defective HR or NHEJ. Additionally, the H3K27M resultant gliomas showed distinctive differences in increased brain tumor penetrance and diffusion. Through RNA-sequencing and whole exome sequencing we identify upregulation of genes normally controlled by bivalent gene promoter post-translational modifications, which result in transcriptional alterations in genes important for both neural development and tumorigenesis. Mechanistically, this is done by targeting specific populations of cortical cells that are more susceptible to DNA damage and transformations that may cause additional critical mutations during a limited timeframe of early cortical development which eventually result in HGGs. We provide evidence supporting that BRCA2 functions to provide DSBR and genome stability to the early-born proliferating cortical progenitor cell population, while LIG4 provides the same function but to a lesser extent to progenitor cells and more so to post-mitotic neurons. Since, epigenetic regulation is tightly connected with neural development and differentiation, we propose the specific genes that H3K27M effects may differ depending on the time period and particular cell state from which the HGG initiates. We believe this contributes to reduced heterogeneity in glioma expression signatures with H3K27M in addition to either HR- or NHEJ-deficiency. Ultimately this work highlights the power of inducible genetically engineered mouse models as an approach to better understand the complexities of providing a connection between genome instability and gliomagenesis

    Filling the Gap in Crisis Intervention: Horizon Homes, Inc. Proposal for SCCBI Crisis Services

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    In late April 2010, the South Central Crisis Center operated in Mankato, MN under state operated services (SOS) closed its doors. The closing of the crisis center left a gap in mental health services, particularly for the ten counties it specifically served. Legislators in the Mankato area, specifically Kathy Sheran worked hard to put together a block grant through the Health and Human Services Act, which would allow additional funding for the reopening of the crisis center. Given that the grant went though, the operation of the new crisis center would be overseen by the South Central Community Based Initiative (SCCBI). In late April 2010, the South Central Community Based Initiative (SCCBI) announced a request for proposal (RFP) for crisis services whihc would include taking over the crisis center. The SCCBI was in search of a mental health agency that would assume daily operation and management of crisis services for the 10-county region. Horizon Homes, Inc. chose to submit a response to SCCBI\u27s RFP for crisis services

    The Optimal Flight Training Experience

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    Up to 80 percent of those who begin flight training drop out without ever earning a pilot certificate. That’s an alarming and unsustainable statistic for schools, instructors, and the entire aviation industry. But it’s also a figure we believe we can change. The reasons for the high dropout rate are complex and include lack of perceived value, ineffective instruction, lack of customer focus, and failure to educate students as consumers, among others. The concerns are not new, but many flight schools have failed to effectively address these and other issues that affect student performance and retention. Why? Because very often the schools themselves lack the tools, knowledge, skills, and support to make the changes needed to deliver a better training experience. Research into the differences between struggling and successful flight schools conducted for AOPA in 2016 confirms that notion. In response to in-depth phone interviews, flight schools produced a long and varied list of concerns and needs around tracking student progress, financial management, improving customer service, expanding business skills, marketing, managing personnel, safety and business oversight, and airport relations, among others. We believe the industry can help schools deliver an optimized training experience—one that leaves students feeling good about their investment in training and excited to take the next steps. With the right help schools can grow, attract more students, and ensure that more of the students who start flying not only earn a certificate but also become active, engaged, and safe members of the aviation community

    Practitioners\u27 Perceptions of Older Male Batterers and Related Factors: An Exploratory Study

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    This was an exploratory study to determine: if mental health practitioners were serving older men who batter; if the practitioners perceived that there were characteristics that differentiated older men who batter from younger men who batter; if these characteristics impacted treatment outcomes and if so, what treatment approaches should be used. Four family violence practitioners participated in a semi-structured interview. The initial findings indicated that: (l) older men who batter comprised a very small proportion of the practitioner\u27s clientele, may be due to fewer older partners utilizing law enforcement assistance; (2) practitioners perceived little difference in characteristics between older men who batter and younger men who batter; and (3) treatment approaches for older men who batter do not need to be altered from those used with younger men who batter. Additional studies utilizing larger samples and varied methodologies are needed to better understand the understudied population of older men who batter

    Die Weltwirtschaftskrise aus geldtheoretischer Sicht

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