57 research outputs found

    Housing Availability and Homelessness in Nevada

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    The first edition of Housing Availability and Homelessness in Nevada was written in 2005 amid economic boom times and rapid population growth. At the publication of this revision, in 2011, Nevadans face crisis-level economic conditions profoundly affecting how we evaluate housing conditions in the Silver State. Hundreds of thousands of people have lost their homes and tens of thousands are jobless and without benefits, putting them at greater risk of homelessness (Associated Press, 2011, Silva, 2011, Sermons and Witte, 2011). Housing availability and homelessness are social concerns looming larger than six years ago

    The Relationship Between Instruction Specificity and Resistiveness to Care During Activities of Daily Living in Persons with Dementia

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    It is common for persons with dementia to display resistant behaviors during activities of daily living (ADLs) and caregiver communication skills can influence the likelihood of these behaviors. Previous research suggests that the type of instructions issued by caregivers is related to rates of compliance during ADLs in persons with dementia. It is unclear, however, if these instruction types affect the likelihood resistiveness to care (RTC) during ADLs. The purpose of the current study was to examine how the use of different types of instructions relate to instances of RTC during ADLs. Results indicated that vague and ambiguous instructions (i.e., beta instructions) were more likely to precede and follow physical aggression compared to instructions that were more specific, clear and feasible (i.e., alpha instructions). Results also indicated that alpha instructions were more likely to precede verbal agitation. These findings have implications for communication training programs for caregivers working with persons with dementia

    IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals

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    Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced

    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

    A novel Alzheimer disease locus located near the gene encoding tau protein

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE Δ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE Δ4+ (10 352 cases and 9207 controls) and APOE Δ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE Δ4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE Δ4+: 1250 cases and 536 controls; APOE Δ4-: 718 cases and 1699 controls). Among APOE Δ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE Δ4+ subjects (CR1 and CLU) or APOE Δ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≀1.3 × 10-8), frontal cortex (P≀1.3 × 10-9) and temporal cortex (P≀1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE Δ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

    Radiotherapy for Prostate Cancer: is it ‘what you do’ or ‘the way that you do it’? A UK Perspective on Technique and Quality Assurance

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    Full circle: returning the power of oral history to the community of Big Lagoon, California through tsunami education and planning

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    Thesis (M.A.)--Humboldt State University, Social Science: Environment and Community, 2012In the last decade, we have become very aware of tsunami and the danger they pose for coastal communities. My research revealed a rich oral history of tsunami from the Yurok, Chetco and Tolowa tribes who still reside along the northwest coasts of California and Oregon. Geologic evidence of the area further supports these tsunami stories. The oral history of tsunami was an important tool of survival education within these tribes. Inspired by the Native American stories and the recent tsunami disasters, my project focused on creating an education campaign in tsunami awareness, planning and hazard reduction in the community of Big Lagoon. In association with the Redwood Coast Tsunami Work Group (RCTWG), I initiated contact with members and agencies in the Big Lagoon community including Big Lagoon Rancheria, Big Lagoon School, Big Lagoon Park Company and Big Lagoon County Park to begin the process of public education, mapping out and testing the best evacuation routes for each area, installing warning signage and holding community evacuation drills. During all phases of the project, I employed avenues of modern story-telling, including pamphlets, articles in newspapers, and internet and television coverage to get the word out to the local community and the community at large. Due to these grassroots efforts, the community of Big Lagoon now has a greater awareness of tsunami, knowledge of safe locations and routes to reach them and consistent evacuation route signage. Through the process of the TsunamiReady program (a trademark of the National Weather Service) the Big Lagoon community was declared a TsunamiReady community by the Eureka, California branch of the National Weather Service on March 26, 2010

    Le RĂŽle de la France dans la poudriĂšre caucasienne

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    The following essay was written in response to the events that transpired in August 2008 between the Georgian and Russian governments. After a long history of tension between the two governments concerning the two separatist provinces, Abkhazia and South Ossetia, open conflict erupted causing great pressure on international leaders to find a solution. President Nicholas Sarkozy is under particular scrutiny due to France’s possession of the European Union presidency. In the aftermath of the conflict this essay examines three main concerns in continuing to work with the two governments: energy, economy, and power politics. The dependency of Georgia and Russia has caused a long standing idea of Russian power over the region. Current assessments show that this power Russia holds is important worldwide in the international scene, and leaders are evaluating how to ensure Russian power does not become too strong. Through the history of the relationship between Russia and Georgia and the current actions of international leaders a path for further action is presented

    Genetic modification of dendritic cells through the directed differentiation of embryonic stem cells

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    Recent years have witnessed a progressive acceptance of the dual role played by dendritic cells (DC) in the initiation of immune responses and their specific attenuation through the induction of immunological tolerance. Nevertheless, as terminally differentiated cells of the myeloid lineage, DC share with macrophages an inherent resistance to genetic modification, greatly restricting strategies available for studying their physiology and function. Consequently, little is known of the molecular interactions provided by DC that underlie the critical decision between tolerance and immunity. Embryonic stem (ES) cells are, by contrast, relatively amenable to genetic modification. Furthermore, their propensity for self-renewal, one of the cardinal features of a stem cell, permits cloning at the single cell level and the rational design of ES cell lines, uniformly expressing a desired, mutant phenotype. Here, we describe how another defining property of ES cells, their demonstrable pluripotency, may be harnessed for their directed differentiation along the DC pathway, enabling the generation of limitless numbers of DC faithfully expressing candidate genes of interest. The protocols we outline in this chapter may, therefore, offer new opportunities for dissecting the biology of DC and the molecular basis of their unique properties
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