Native American education between assimilation and self-determination - Schooling in tribal communities in the state of Arizona

The paper explores the situation of education of Native American students in Arizona, USA. This entails an attention to some historical and to current developments. Focusing on certain school types in tribal communities and on the understanding of education from a native perspective, the aim is to show the dichotomy between self-determination and assimilation in educational processes and the challenge for the tribes to find own forms of schooling to prepare the young generations for future developments that benefit them and their tribes. The four school types, which are presented in the ... text, the author investigated on the Hopi and the Navajo reservation and in a Tohono O\u27odham community in Arizona in 2006. The intention of the field study was to capture a range of current schooling possibilities. Therefore schools were chosen that present the common types of today\u27s native institutions as well as their use by different tribal communities. In addition to half-standardized interviews with teachers of the schools the method of open observation in classrooms and in community events as well as print media analysis were used. (DIPF/Orig.

Damage-induced signalling mechanisms in the neonatal rat cochlea.

Sound overstimulation and exposure to ototoxic drugs damage cochlear hair cells (HCs) and cause their death. The surrounding support cells maintain an epithelial barrier and the appropriate physiological environment for surviving HCs during pathological conditions. Coordination of this homeostatic process requires cellular signalling. However, the signalling events that are activated during damage in the mammalian cochlea, are poorly understood. Neonatal rat cochlear explants were subjected to mechanical damage or exposed to neomycin - an ototoxin. Mechanical damage triggered the immediate propagation of an intercellular wave of increased intracellular Ca2+ from the lesion site into distinct cochlear regions. The properties of the Ca2+ wave and the source of Ca2+ required were specific to the cochlear region. IP3-mediated release from intracellular stores and influx of extracellular Ca2+ contribute differentially to the rise in intracellular Ca2+. The release of extracellular ATP is crucial for the propagation of the damage-induced Ca2+ wave. Gap junctions or connexin hemichannels also contribute to its formation. A subsequent damage-induced signalling event is the transient phosphorylation of ERK1/2 that arises within minutes of the insult occurring in support cells specifically. Similarly to the formation of the Ca2+ wave, release of extracellular ATP and gap junctions are critical for ERK1/2 activation. UTP-induced activation of ERK1/2 reveals the involvement of P2Y receptors. In addition, a requirement for the influx of extracellular Ca2+ also suggests a role for ion channels - potentially P2X receptors. P2X2,3,4 and P2Y2.4, n receptors were expressed in cochlear explants with P2X2 and P2Y2 being exclusive to support cells. Damage-induced currents were recorded from Deiters' cells in a syncytium during mechanical damage of the cochlea. Finally, when HCs were specifically targeted using neomycin, ERK1/2 activation occurred in support cells surrounding pyknotic HC nuclei. Inhibition of ERK1/2 delayed HC death

Oxidative and Endoplasmic Reticulum Stress Represent Novel Therapeutic Targets for Choroideremia

Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy, affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, with no approved therapy. CHM is caused by mutations in the CHM gene, which encodes the ubiquitously expressed Rab escort protein 1 (REP1). REP1 is involved in prenylation, a post-translational modification of Rab proteins, and plays an essential role in intracellular trafficking. In this study, we examined oxidative and endoplasmic reticulum (ER) stress pathways in chmru848 zebrafish and CHMY42X patient fibroblasts, and screened a number of neuroprotectants for their ability to reduce stress. The expression of the oxidative stress markers txn, cat and sod3a, and the ER stress markers bip, atf4 and atf6, were dysregulated in chmru848 fish. The expression of SOD2 was also reduced in CHMY42X fibroblasts, along with reduced BIP and increased CHOP expression. The lack of REP1 is associated with defects in vesicular trafficking, photoreceptor outer segment phagocytosis and melanosome transport, leading to increased levels of stress within the retina and RPE. Drugs targeting oxidative and ER stress pathways represent novel therapeutic avenues

The free-linking task: a graph-inspired method for generating non-disjoint similarity data with food products

"Free sorting", in which subjects are asked to sort a set of items into groups of "most similar" items, is increasingly popular as a technique for profiling sets of foods. However, free sorting implies an unrealistic model of sample similarity: that similarity is purely binary (is/is not similar) and that similarity is fully transitive (similarities {A, B} and {B, C} imply {A, C}). This paper proposes a new method of rapid similarity testing -- the "free-linking" task -- that solves both problems: in free linking, subjects draw a similarity graph in which they connect pairs of samples with a line if they are similar, according to the subject s individual criteria. This simple task provides a more realistic model of similarity which allows degrees of similarity through the graph distance metric and does not require transitive similarity. In two pilot studies with spice blends (10 samples, 58 subjects) and chocolate bars (10 samples, 63 subjects), free linking and free sorting are evaluated and compared using DISTATIS, RVb, and the graph parameters degree, transitivity, and connectivity; subjects also indicated their preferences and ease-of-use for the tasks. In both studies, the first two dimensions of the DISTATIS consensus were highly comparable across tasks; however, free linking provided more discrimination in dimensions three and four. RVb stability was equivalent for the two methods. Graph statistics indicated that free linking had greater discrimination power: on average subjects made similarity groupings with lower degree, lower transitivity, and higher connectivity for free linking in both studies. However, subjects did overall find free sorting easier and liked it more, indicating a higher cognitive difficulty of free linking. The free-linking task, therefore, provides more robust, realistic similarity maps at the cost of higher panelist effort, and should prove a valuable alternative for rapid sensory assessment of product sets.Agencia Estatal de Investigació

PAX6 disease models for aniridia

Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently. Progressive sight loss can arise from cataracts, glaucoma, and aniridia-related keratopathy, which can be managed conservatively or through surgical intervention. The vast majority of patients harbor heterozygous mutations involving the PAX6 gene, which is considered the master transcription factor of early eye development. Over the past decades, several disease models have been investigated to gain a better understanding of the molecular pathophysiology, including several mouse and zebrafish strains and, more recently, human-induced pluripotent stem cells (hiPSCs) derived from aniridia patients. The latter provides a more faithful cellular system to study early human eye development. This review outlines the main aniridia-related animal and cellular models used to study aniridia and highlights the key discoveries that are bringing us closer to a therapy for patients

Effectiveness and Tolerability of Tapentadol Prolonged Release Compared With Prior Opioid Therapy for the Management of Severe, Chronic Osteoarthritis Pain

BACKGROUND: Tapentadol prolonged release (PR; 100–250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment. OBJECTIVE: The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50–250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability. METHODS: This open-label, phase 3b study (NCT00982280) was conducted from October 2009 through June 2010 (prematurely terminated due to slow recruitment and study drug shortages) in clinical care settings in Europe and Australia. The study population included patients with severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening, responded to therapy (average pain intensity [11-point numerical rating scale-3 (NRS-3)] ≤5 at screening), and reported opioid-related adverse effects as their reason for changing analgesics. Patients switched directly from WHO step III therapy to tapentadol. Patients received oral tapentadol PR (50–250 mg twice daily) during 5-week titration and 7-week maintenance periods. Oral tapentadol immediate release (IR) was permitted (≤twice/day, ≥4 h apart) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids (combined dose of tapentadol [PR and IR] ≤500 mg/day). This study was planned to evaluate conversion to tapentadol PR, based on responder rate 1 (percentage of patients with same/less pain [NRS-3] versus Week −1) at Week 6 (primary endpoint), adverse events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids (PR and PR plus IR formulations). RESULTS: Of 82 patients enrolled, 63 received study medication. In the per-protocol population, responder rate 1 at Week 6 (last observation carried forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis population. In the safety population, prevalence of AEs reported as associated with prior opioids at Week −1 (reasons for rotation) and related to tapentadol treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 %), and withdrawal of consent (1.6 %). CONCLUSIONS: Significant improvements in effectiveness were observed for tapentadol PR (50–250 mg twice daily) versus WHO step III opioids in patients with severe, chronic osteoarthritis knee pain who previously responded to WHO step III therapy. Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40261-013-0102-0) contains supplementary material, which is available to authorized users