Within the Realm of Possibility: Magic and Mediation in Native American and Chicano/A Literature.

Bloodlines create an overlap in Native American and Chicano/a history, but this dissertation studies these ethnic groups together for reasons beyond this. Native Americans and Chicanos/as share more than blood; overlaps occur in language, religion, and United States geography. Psychic geography for each group also presents a kinship, for in the search for a redemptive personal identity (to stand against the forcible near-extinction of Native Americans and the cultural dismissal of Chicanos/as by their native land) each cultural group recognizes its difference. Having very little in dominant culture upon which to build an identity, Native Americans and Chicanos/as have turned inward to create their own texts of rediscovery. To achieve this personal rediscovery, Chicano/a and Native American writers often turn to magical realism. Through an examination of contemporary novels written by and about Native Americans and Chicanos/as, this dissertation explores the impact of magical realism on cultural mediation. Whether because of mixed ancestry or a liminal, borderlands setting, characters of the novels discussed in Chapters Two and Three face conflicting cultures (their own culture versus the dominant culture), and, because of magical intervention, are able to emerge from their respective conflicts with a blended sense of identity, taking the best each culture has to offer to form a new perspective. The works presented in Chapter Four study what I believe to be a uniquely Chicano/a trait: nearly magical writing. Chapter Two presents four characters and five novels as examples of the coming of age story, or bildungsroman, and the role of magical realism in this rite of passage. They are Rudolfo Anaya\u27s Bless Me, Ultima, Louise Erdrich\u27s The Bingo Palace and Love Medicine, Linda Hogan\u27s Solar Storms, and Ana Castillo\u27s So Far From God. Chapter Three explores adult reactions to magical realism, noting the differences in Chicano/a and Native American perspectives. Under discussion are Ana Castillo\u27s So Far From God, Leslie Marmon Silko\u27s Ceremony, and Paula Gunn Allen\u27s The Woman Who Owned the Shadows. The final chapter addresses what I have termed nearly magical literature, using Sandra Cisneros\u27 Woman Hollering Creek to illustrate this idea

Comparison of the generic neuronal differentiation and neuron subtype specification functions of mammalian achaete-scute and atonal homologs in cultured neural progenitor cells

In the vertebrate peripheral nervous system, the proneural genes neurogenin 1 and neurogenin 2 (Ngn1 and Ngn2), and Mash1 are required for sensory and autonomic neurogenesis, respectively. In cultures of neural tube-derived, primitive PNS progenitors NGNs promote expression of sensory markers and MASH1 that of autonomic markers. These effects do not simply reflect enhanced neuronal differentiation, suggesting that both bHLH factors also specify neuronal identity like their Drosophila counterparts. At high concentrations of BMP2 or in neural crest stem cells (NCSCs), however, NGNs like MASH1 promote only autonomic marker expression. These data suggest that that the identity specification function of NGNs is more sensitive to context than is that of MASH1. In NCSCs, MASH1 is more sensitive to Notch-mediated inhibition of neurogenesis and cell cycle arrest, than are the NGNs. Thus, the two proneural genes differ in other functional properties besides the neuron subtype identities they can promote. These properties may explain cellular differences between MASH1- and NGN-dependent lineages in the timing of neuronal differentiation and cell cycle exit

Identification of dividing, determined sensory neuron precursors in the mammalian neural crest

Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo

Rethinking Our Waterways - best practices for collaborative approaches to watershed planning

Water is the lifeblood of communities. We depend on it, we value it, and with growing awareness of the potential impacts of population growth, climate change and other pressures within our water resources and watersheds, we must work together to effectively manage and steward our water resources into the future. To address the complexities inherent to watershed and water resource planning at the local scale, the Fraser Basin Council has developed a comprehensive watershed-planning guide to assist organizations and individuals to:• Understand the value of water and watershed planning• Navigate the diversity of current and emerging water issues• Understand the range of planning options available in British Columbia; and,• Build capacity to develop and implement plans to strengthen watershed health and community sustainability. Bringing the right people together to discuss the wide ranging issues within a watershed is no easy task, but when done well, it can be an efficient, credible, and cost effective way to develop integrated and robust solutions that are relevant to, and supported by, the community. Key principles for collaborative multi-stakeholder processes include:• shared purpose and clearly defined incentives to participate;• commitment to the collaborative process;• collectively designed and determined process that suits the needs of the participants; • establish realistic milestones and deadlines to track progress throughout the process; • effective process coordination, oversight and management, including a trusted and credible facilitator.The Shuswap Lake Integrated Planning Process (SLIPP) is a multi-agency planning process focused on improving the health and prosperity of the lakes in the Shuswap watershed in BC’s central interior region. SLIPP provides on on-the-ground example of collaboration for watershed planning and ultimately, improved watershed health. The structure, approach and outcomes from SLIPP are unique in BC and the key lessons are relevant across a wide spectrum of communities, regions and initiatives

Mechanism of the Inhibition of Ca2+-Activated Cl− Currents by Phosphorylation in Pulmonary Arterial Smooth Muscle Cells

The aim of the present study was to provide a mechanistic insight into how phosphatase activity influences calcium-activated chloride channels in rabbit pulmonary artery myocytes. Calcium-dependent Cl− currents (IClCa) were evoked by pipette solutions containing concentrations between 20 and 1000 nM Ca2+ and the calcium and voltage dependence was determined. Under control conditions with pipette solutions containing ATP and 500 nM Ca2+, IClCa was evoked immediately upon membrane rupture but then exhibited marked rundown to ∼20% of initial values. In contrast, when phosphorylation was prohibited by using pipette solutions containing adenosine 5′-(β,γ-imido)-triphosphate (AMP-PNP) or with ATP omitted, the rundown was severely impaired, and after 20 min dialysis, IClCa was ∼100% of initial levels. IClCa recorded with AMP-PNP–containing pipette solutions were significantly larger than control currents and had faster kinetics at positive potentials and slower deactivation kinetics at negative potentials. The marked increase in IClCa was due to a negative shift in the voltage dependence of activation and not due to an increase in the apparent binding affinity for Ca2+. Mathematical simulations were carried out based on gating schemes involving voltage-independent binding of three Ca2+, each binding step resulting in channel opening at fixed calcium but progressively greater “on” rates, and voltage-dependent closing steps (“off” rates). Our model reproduced well the Ca2+ and voltage dependence of IClCa as well as its kinetic properties. The impact of global phosphorylation could be well mimicked by alterations in the magnitude, voltage dependence, and state of the gating variable of the channel closure rates. These data reveal that the phosphorylation status of the Ca2+-activated Cl− channel complex influences current generation dramatically through one or more critical voltage-dependent steps

Effect of membrane character and solution chemistry on microfiltration performance

To help understand and predict the role of natural organic matter (NOM) in the fouling of low-pressure membranes, experiments were carried out with an apparatus that incorporates automatic backwashing and long filtration runs. Three hollow fibre membranes of varying character were included in the study, and the filtration of two different surface waters was compared. The hydrophilic membrane had greater flux recovery after backwashing than the hydrophobic membranes, but the efficiency of backwashing decreased at extended filtration times. NOM concentration of these waters (7.9 and 9.1 mg/L) had little effect on the flux of the membranes at extended filtration times, as backwashing of the membrane restored the flux to similar values regardless of the NOM concentration. The solution pH also had little effect at extended filtration times. The backwashing efficiency of the hydrophilic membrane was dramatically different for the two waters, and the presence of colloid NOM alone could not explain these differences. It is proposed that colloidal NOM forms a filter cake on the surface of the membranes and that small molecular weight organics that have an adsorption peak at 220 nm but not 254 nm were responsible for “gluing” the colloids to the membrane surface. Alum coagulation improved membrane performance in all instances, and this was suggested to be because coagulation reduced the concentration of “glue” that holds the organic colloids to the membrane surface

Minimising the use of physical restraint in acute mental health services: The outcome of a restraint reduction programme (‘REsTRAIN YOURSELF)

Background Physical restraint is a coercive intervention used to prevent individuals from harming themselves or others. However, serious adverse effects have been reported. Minimising the use of restraint requires a multimodal approach to target both organisational and individual factors. The ‘Six Core Strategies’ developed in America, underpinned by prevention and trauma informed principles, is one such approach. Objective An adapted version of the Six Core Strategies was developed and its impact upon physical restraint usage in mental health Trusts in the United Kingdom evaluated. This became known as ‘REsTRAIN YOURSELF. The hypothesis was that restraint would be reduced by 40% on the implementation wards over a six-month period. Design A non-randomised controlled trial design was employed. Setting Fourteen, adult, mental health wards from seven mental health hospitals in the North West of England took part in the study. Two acute care wards were targeted from all eligible acute wards within each site in negotiation with each Trust. The intervention wards (total n = 144 beds, mean = 20.1 beds per ward) and control wards (total n = 147 beds, mean = 21.0 beds per ward) were primarily mixed gender but included single sex wards also (2 female-only and 1 male-only in each group). All wards offered pharmacological and psychosocial interventions over short admission durations (circa 15 days) for patients with a mixture of enduring mental health problems. Method As part of a pre and post-test method, physical restraint figures were collected using prospective, routine hospital records before and 6 months after the intervention. Restraint rates on seven wards receiving the REsTRAIN YOURSELF intervention were compared with those on seven control wards over three study phases (baseline, implementation and adoption). Results In total, 1680 restraint incidents were logged over the study period. The restraint rate was significantly lower on the intervention wards in the adoption phase (6.62 events/1000 bed-days, 95% CI 5.53-7.72) compared to the baseline phase (9.38, 95% CI 8.19-10.55). Across all implementation wards there was an average reduction of restraint by 22%, with some wards showing a reduction of 60% and others less so (8%). The association between ward type and study phase was statistically significant. Conclusion In conclusion, it is possible that reductions in the use of physical restraint are achievable using a model such as the Six Core Strategies. This approach can be adapted for global settings and changes can be sustained over time with continued support

The U&I study: study protocol for a feasibility randomised controlled trial of a pre-cognitive behavioural therapy digital ‘informed choice’ intervention to improve attitudes towards uptake and implementation of CBT for psychosis

Background: At least 40% of people with psychosis have persistent distressing symptoms despite optimal medication treatment. Cognitive Behaviour Therapy for psychosis (CBTp) is the only NICE recommended individual therapy for psychosis, with effects on symptoms, distress and quality of life. Yet fewer than 20% of service-users receive it and 94% of trusts struggle to provide it. Of those offered it, 22-43% refuse or do not attend. We have developed a new pre-CBTp informed choice intervention to address knowledge and attitudes that influence uptake and implementation and now want to test it in a feasibility trial. Methods: The design is a 2-arm, feasibility RCT, with 1:1 randomisation, stratified by participant group and site. Participants are 40 psychosis patients and 40 clinicians, who are ambivalent towards uptake or implementation of CBTp. Sites are community and inpatient services in Sussex and London. The intervention is a pre-CBT digital psychoeducation intervention designed to address identified knowledge and attitudinal barriers to uptake and implementation of CBTp, incorporating behaviour change mechanisms, and supported by animated introductory, patient and clinician stories. The comparator is the NHS choices website for CBT. The primary aim is to assess clinical feasibility (recruitment, randomization, acceptability, use, delivery, outcome measurement, retention). A secondary aim is a preliminary evaluation of efficacy. Outcomes will be assessed at baseline, post-intervention, and one-month follow up (blind to treatment arm). The primary efficacy outcome is likelihood of offering/taking up CBTp. Secondary outcomes include knowledge and attitudes towards CBTp; illness perceptions; empowerment; psychological wellbeing (patients only); CBTp implementation (clinicians only). Use of the intervention and CBT behaviours during the follow-up period will be recorded, and captured in a feedback questionnaire. Use, acceptability and experience of outcome assessment will be explored in qualitative interviews with participants (n = 6 per group). The efficacy evaluation will report descriptive data, key model parameters and 95% Highest Probability Density intervals in a Bayesian growth model. Discussion: This is the first feasibility trial of a digital ‘informed choice’ decision aid for the implementation of CBTp. If the trial proves feasible and demonstrates preliminary evidence of efficacy, a large multi-site trial will be warranted

Molecular and functional correction of a deep intronic splicing mutation in CFTR by CRISPR-Cas9 gene editing

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site. This mutation was corrected in CF primary cells homozygous for this mutation by delivering pairs of guide RNAs (gRNAs) with Cas9 protein in ribonucleoprotein (RNP) complexes that introduce double-strand breaks to flanking sites to excise the 3849+10kb C>T mutation, followed by DNA repair by the non-homologous end-joining pathway, which functions in all cells of the airway epithelium. RNP complexes were delivered to CF basal epithelial cell by a non-viral, receptor-targeted nanocomplex comprising a formulation of targeting peptides and lipids. Canonical CFTR mRNA splicing was, thus, restored leading to the restoration of CFTR protein expression with concomitant restoration of electrophysiological function in airway epithelial air-liquid interface cultures. Off-target editing was not detected by Sanger sequencing of in silico-selected genomic sites with the highest sequence similarities to the gRNAs, although more sensitive unbiased whole genome sequencing methods would be required for possible translational developments. This approach could potentially be used to correct aberrant splicing signals in several other CF mutations and other genetic disorders where deep-intronic mutations are pathogenic

Bridging the digital divide in psychological therapies: observational study of engagement with the SlowMo mobile app for paranoia in psychosis

Background: Marginalized groups are more likely to experience problems with technology-related access, motivation, and skills. This is known as the “digital divide.” Technology-related exclusion is a potential barrier to the equitable implementation of digital health. SlowMo therapy was developed with an inclusive, human-centered design to optimize accessibility and bridge the “digital divide.” SlowMo is an effective, blended digital psychological therapy for paranoia in psychosis. Objective: This study explores the “digital divide” and mobile app engagement in the SlowMo randomized controlled trial. Methods: Digital literacy was assessed at baseline, and a multidimensional assessment of engagement (ie, adherence [via system analytics and self-report] and self-reported user experience) was conducted at 12 weeks after therapy. Engagement was investigated in relation to demographics (ie, gender, age, ethnicity, and paranoia severity). Results: Digital literacy data demonstrated that technology use and confidence were lower in Black people and older people (n=168). The engagement findings indicated that 80.7% (96/119) of therapy completers met the a priori analytics adherence criteria. However, analytics adherence did not differ by demographics. High rates of user experience were reported overall (overall score: mean 75%, SD 17.1%; n=82). No differences in user experience were found for ethnicity, age, or paranoia severity, although self-reported app use, enjoyment, and usefulness were higher in women than in men. Conclusions: This study identified technology-related inequalities related to age and ethnicity, which did not influence engagement with SlowMo, suggesting that the therapy design bridged the “digital divide.” Intervention design may moderate the influence of individual differences on engagement. We recommend the adoption of inclusive, human-centered design to reduce the impact of the “digital divide” on therapy outcomes