Optimizing The Nasal Allergen Challenge Model For The Study Of Allergic Rhinitis

Background The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) uses a Nasal Allergen Challenge (NAC) model to study the pathophysiology of AR and provides proof of concept for novel therapeutics. The NAC model needs to ensure optimal participant qualification, allergen challenge, clinical symptoms capture and biological samples collection. Repeatability of the protocol is key to ensuring unbiased efficacy analysis of novel therapeutics. The effect of allergen challenge on IL-33 gene expression and its relation to IL1RL1 receptor and cytokine secretion was investigated. Methods Several iterations of the NAC protocol was tested, comparing variations of qualifying criteria based on the Total Nasal Symptom Score (TNSS) and Peak Nasal Inspiratory Flow (PNIF). The lowest allergen concentration was delivered and TNSS and PNIF recorded 15 minutes later. Participants qualified if the particular criteria for the protocol were met, otherwise the next higher allergen concentration (4-fold increase), was administered until the targets were reached. Participants returned for a NAC visit and received varying allergen challenge concentrations depending on the protocol, TNSS/PNIF were recorded at 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours, a 24 hour time point was added in later iterations. Repeatability was evaluated using a 3-4week interval between screening, NAC1, and NAC2 visits. Various biomarker samples were collected. Results A combined TNSS and PNIF criterion was more successful in qualifying participants. The cumulative allergen challenge (CAC) protocol proved more reliable in producing a robust clinical and biomarker response. Repeatability of the CAC protocol was achieved with a 3-week interval between visits, on a clinical and biological basis. IL-33 cytokine is an important biomarker in initiating the inflammatory response in AR in humans. IL-33 and IL1RL1 expression might employ a negative feedback mechanism in human nasal epithelial cells. Comparing the clinical and biological response to ragweed vs cat allergen challenge, proved the CAC protocol’s suitability for use employing different allergens. Conclusion The AR-CIC’s CAC protocol is an effective method of studying AR, capable of generating measurable and repeatable clinical and biomarker responses, enabling better understanding of AR pathophysiology and ensuring that any change would be purely due to medication under investigation in a clinical trial setting.

Admittance Control for Robotic Loading: Design and Experiments with a 1-Tonne Loader and a 14-Tonne LHD

This paper describes the design, tuning, and extensive field testing of an admittance-based Autonomous Loading Controller (ALC) for robotic excavation. Several iterations of the ALC were tuned and tested in fragmented rock piles—similar to those found in operating mines—by using both a robotic 1-tonne capacity Kubota R520S diesel-hydraulic surface loader and a 14-tonne capacity Atlas Copco ST14 underground load-haul-dump (LHD) machine. On the R520S loader, the ALC increased payload by 18 % with greater consistency, although with more energy expended and longer dig times when compared with digging at maximum actuator velocity. On the ST14 LHD, the ALC took 61 % less time to load 39 % more payload when compared to a single manual operator. The manual operator made 28 dig attempts by using three different digging strategies, and had one failed dig. The tuned ALC made 26 dig attempts at 10 and 11 MN target force levels. All 10 11 MN digs succeeded while 6 of the 16 10 MN digs failed. The results presented in this paper suggest that the admittance-based ALC is more productive and consistent than manual operators, but that care should be taken when detecting entry into the muck pile

An Ergonomic Evaluation of a Wrist Brace for Canadian Tree Planters

Tree planting is one of the most physically demanding occupations in Canada and as a result, tree planters are at an elevated risk of injury, specifically at the wrist. Wrist injuries develop on account of the highly repetitive nature of the job, as well as other musculoskeletal risk factors including non-neutral wrist postures and high impact forces sustained at the wrist during shovel-ground impact. As a result, wrist brace use has become common among planters, in an effort to limit deviated wrist postures while also providing enhanced stability at the wrist. The external stability provided by a wrist brace is thought to reduce the muscular effort required to provide stiffness at the wrist during shovel-ground impact. Since these prospective benefits have not been formally investigated, the purpose of this study was to determine the effect of a wrist brace on wrist posture, muscle activity, and joint rotational stiffness about the wrist joint (for two degrees of freedom: flexion/extension and ulnar/radial deviation). We hypothesized that the brace would promote more neutrally aligned wrist angles, and that muscle activity and joint rotational stiffness would also decrease when participants wore the brace. Fourteen tree planters with at least one season of experience were recruited to complete two planting conditions in a laboratory setting: one condition while wearing the brace (with brace, WB) and one condition without the brace (no brace, NB). The results from this study showed that at shovel-ground impact muscle activity trended towards increasing in three muscles when participants wore the brace. Additionally, wrist angles improved about the flexion/extension axis of rotation while increasing in deviation about the ulnar/radial axis of rotation when participants wore the brace. Joint rotational stiffness increased when participants wore the wrist brace. Participants from this study indicated difficulty gripping the shovel due to the bulk of the wrist brace, and this feature is discussed with possible suggestions for future iterations of design. In addition to grip diameter this analysis also prompts the suggestion that hand length and experience should also be considered in the design of tree planting tools, specifically an ergonomic aid such as a wrist brace.

Crises of In/Humanity: Posthumanism, Afrofuturism, and Science and/as Fiction

This thesis engages black critical thought on the human and its contemporary iterations in posthumanism and transhumanism. It articulates five categories of analysis: displace, interrupt, disrupt, expand, and wither. Each is meant to allude to the generative potential in different iterations of black thought that engages the human. Working through Sylvia Wynter’s theories of the rise of Man-as-human in particular, the project highlights how black thought on the human displaces the uncritical whiteness of posthumanist thought. It argues that Afrofuturism has the potential to interrupt the linear progression from human to posthuman and that Octavia Butler’s Fledgling proffers a narrative of race as a technology that disrupts the presumed post-raciality of posthumanism and transhumanism. It then contends that Katherine McKittrick’s rearticulation of the Promise of Science can be extended to incorporate the promise of science fiction. In so doing, it avers that a more curated conversation between McKittrick and Wynter, one already ongoing, and Octavia Butler, through Mind of My Mind from her Patternist series, expands our notions of the human as a category even at the risk of seeing it wither as a politic or praxis. It ends on a speculative note meant to imagine the possibilities within the promise of science fiction.