435 resultados para Kingston
Resumo:
Abnormal maternal inflammation during pregnancy is linked to complications such as preeclampsia and fetal growth restriction. There is growing evidence that insulin resistance is also associated with a heightened inflammatory state, and is linked to pregnancy complications such as gestational diabetes. This study tested the hypothesis that abnormal inflammation during pregnancy is causally linked to elevations in blood glucose and insulin resistance. To induce a state of abnormal systemic inflammation, bacterial lipopolysaccharide (LPS) was administered to pregnant rats on gestational days (GD) 13.5-16.5. Dams treated with LPS exhibited an abnormal immune response characterized by an elevation in white blood cells, which was linked to reduced fetal weight and increased glucose levels over pregnancy. Abnormal inflammation is characterized by increased levels of circulating pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF) and interleukin-6, which contribute to insulin resistance by inhibiting the insulin signalling pathway. TNF in particular induces a serine phosphorylation (pSer307) of insulin receptor substrate 1 (IRS-1). In our model, insulin resistance was assessed by measuring the extent of pSer307 of IRS-1 and total IRS-1 expression in skeletal muscle, as well as changes in metabolic parameters and pancreas tissue morphology associated with insulin resistance. LPS-treated dams exhibited a significant reduction in IRS-1 expression, elevation in fasting glucose levels, and reduction in insulin sensitivity indices. There were also biologically relevant increases in fasting plasma insulin levels and insulin resistance indices, but not pSer307 of IRS-1 and pancreatic islet size. To determine whether inflammation plays a role in reducing insulin signalling and the other changes associated with LPS administration, etanercept, a TNF antagonist, was administered on GDs 13.5 and 15.5 prior to LPS injections. With the exception of IRS-1 expression, in rats treated with etanercept all of the measured parameters remained at the levels observed in saline controls, indicating a link between abnormal inflammation and insulin resistance. The results of this study support the practice of monitoring the inflammatory conditions of the mother prior to and during pregnancy, and support further investigation into the potential use of anti-inflammatory agents during pregnancy in women at risk of insulin resistance and gestational diabetes.
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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.
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Despite attempts to identify the mechanisms by which obesity leads to the development of Type 2 Diabetes (T2D), it remains unclear why some but not all adults with obesity develop T2D. Given the established associations between visceral adipose tissue (VAT) and liver fat with insulin resistance, we hypothesized that compared to age and obesity matched adults who were non-diabetic (NT2D), adults with T2D would have greater amounts of VAT and liver fat. The International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) aims to study the associations between VAT and liver fat and risk of developing T2D and cardiovascular disease. Four thousand, five hundred and four participants were initially recruited; from this, 2383 White and Asian adults were selected for this ancillary analysis. The NT2D and T2D groups were matched for age, body mass index (BMI) and waist circumference (WC). The T2D and NT2D groups were also compared to participants with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT; IFG/IGT)). Abdominal adipose tissue was measured by computed tomography; liver fat was estimated using computed tomography-derived mean attenuation. Secondary analysis determined whether differences existed between NT2D and T2D groups in VAT and liver fat accumulation within selected BMI categories for Whites and Asians. We report across sex and race, T2D and IFG/IGT groups had elevated VAT and liver fat compared to the NT2D group (p<0.05). VAT was not different between IFG/IGT and T2D groups (p>0.05), however liver fat was greater in the T2D group compared to the IFG/IGT group in both Whites and Asians (p<0.05). Within each BMI category, the T2D group had elevated VAT and liver fat compared to the age and anthropometrically matched NT2D group in both Whites and Asians (p<0.05). With few exceptions, abdominal subcutaneous adipose tissue was not different in the T2D or IFG/IGT groups compared to the NT2D group independent of sex and race. Compared to age and obesity-matched adults who are NT2D, we observe that White and Asian adults with T2D, and those with IFG/IGT, present with greater levels of both VAT and liver fat.
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The eastern Canadian Arctic is home to Canada’s largest Indigenous population, which depends on local freshwater sources for drinking water. However, small watersheds have rarely been analyzed for long-term hydrologic response to changing climate. This study aims to address this issue by examining the Apex River, a small watershed with a long hydroclimatic record, near Iqaluit, Nunavut. Particular emphasis was placed on the long-term changes in climate and river discharge, and the seasonal variability of water sources between two snapshots in time, 1983 and 2013. Long-term hydrological data were obtained from gauge station 10UH002, operated by Environment and Climate Change Canada, and long-term meteorological data were acquired from Environment Canada–operated stations near Iqaluit Airport. Breakpoint analysis suggested that long-term mean annual surface air temperatures have increased since 1994. In contrast, no long-term total precipitation or annual discharge changes were observed. However, river flow initiation and cessation analyses of the Apex River flow season indicates that flow extended into the autumn since the 2000s. The 2013 flow season lasted 44 days longer than the 1983 flow season. Systematic river sampling was undertaken throughout the 2013 thaw season to determine contributing proportions of event (snowmelt or rainfall) and pre-event (baseflow) water to river runoff. Results from the stable isotope hydrograph separation for 2013 were compared to findings for 1983. Snow was the main source of water to the river during the snowmelt period in 1983 and 2013, however baseflow was still an important contributor. Although there was high similarity of water sources early in the season in 1983 and 2013, the two years differed during the autumn. In 2013 there was a high rainfall runoff response that was not present in 1983, suggesting high release of late-season sub-surface water storage and an increased sensitivity to late-season rainfall events in 2013. This research provides insights into the hydrologic response of the Apex River to long-term climatic change, and highlights the need for high-quality precipitation and discharge data for effective long-term hydrological assessment.
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Background and aim: Within the gastrointestinal tract, vagal afferents regulate satiety and food intake via chemical and mechanical mechanisms. Cysteinyl Leukotrienes (CysLTs) are lipid mediators that are believed to regulate food intake and body weight. However, the involvement of vagal afferents in this effect remains to be established. Conversely, Glucagon like peptide-1 (GLP-1) is a satiety and incretin peptide hormone. The effect of obesity on GLP-1 mediated gut-brain signaling has yet to be investigated. Since intestinal vagal afferents’ activity is reduced during obesity, it is intriguing to investigate their responses to GLP-1 in such conditions. Methods: Extracellular recordings were performed on intestinal afferents from normal C57Bl6, low fat fed (LFF), and high fat fed (HFF) mice. To examine the effect on neuronal calcium signaling, calcium-imaging experiments were performed on isolated nodose ganglion neurons. Food intake experiments were conducted using LFF and HFF mice. Oral glucose tolerance tests (OGTT) were carried out. Whole cell patch clamp recordings were performed on nodose ganglion neurons from A) normal C57Bl mice to test the effect of CysLTs on membrane excitability, B) LFF and HFF mice to examine GLP-1 effect on membrane excitability during obesity. c-Fos immunohistochemical techniques were performed to measure the level of neuronal activation in the brainstem of both LFF and HFF mice in response to Ex-4. Results: CysLTs increased intestinal afferent firing rate and mechanosensitivity. In single nodose neuron experiments, CysLTs increased excitability. The GLP-1 agonist Ex-4 significantly decreased food intake in LFF but not HFF mice. However, Ex-4 markedly attenuated the rise in blood glucose in both LFF and HFF mice. The observed increase in nerve firing and mechanosensitivity following the application of GLP-1 and Ex-4 was abolished in HFF mice. Cell membrane excitability was significantly increased by Ex-4 in nodose from LFF but not HFF mice. Ex-4 significantly increased the number of activated neurons in the NTS area of LFF mice but not in their HFF counterparts. Conclusion: The previous observations indicate that the role CysLTs play in regulating satiety is likely to be vagally mediated. Also that satiety, but not incretin, effects of GLP-1 are impaired during obesity.
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Performing Pedagogies was a week-long performance and exhibition series I organized that took place in Kingston, Ontario between March 15th - March 20th 2016. The motivation for this project came from a desire to explore performative modes of experiencing critical, embodied knowledge. The series featured five performances, a long distance collaboration between thirty-one Queen’s undergraduate students and a Vancouver artist-run free school (The School for Eventual Vacancy), a subsequent exhibition, a panel discussion, and a radical performance pedagogy workshop led by co-artistic director of the international performance art troupe, La Pocha Nostra. Artists featured included Golboo Amani, Basil AlZeri, Caitlin Chaisson, Justin Langlois, Saul Garcia-Lopez, Francisco-Fernando Granados, and Andrew Rabyniuk. By curating examples of performance art that variously incorporated embodied pedagogical interventions, I examined the processes of performance as pedagogy. Performing Pedagogies explored interventions into contemporary contours of neoliberal education paradigms through embodied encounters—fostering conversations about the meanings and limitations of knowledge dissemination and education today and posing questions about possibilities for radical pedagogies, embodied knowledge, and counter curricula.
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Interacting with a computer system in the operating room (OR) can be a frustrating experience for a surgeon, who currently has to verbally delegate to an assistant every computer interaction task. This indirect mode of interaction is time consuming, error prone and can lead to poor usability of OR computer systems. This thesis describes the design and evaluation of a joystick-like device that allows direct surgeon control of the computer in the OR. The device was tested extensively in comparison to a mouse and delegated dictation with seven surgeons, eleven residents, and five graduate students. The device contains no electronic parts, is easy to use, is unobtrusive, has no physical connection to the computer and makes use of an existing tool in the OR. We performed a user study to determine its effectiveness in allowing a user to perform all the tasks they would be expected to perform on an OR computer system during a computer-assisted surgery. Dictation was found to be superior to the joystick in qualitative measures, but the joystick was preferred over dictation in user satisfaction responses. The mouse outperformed both joystick and dictation, but it is not a readily accepted modality in the OR.
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Countering the trend in contemporary ecocriticism to advance realism as an environmentally responsible mode of representation, this essay argues that the anti-realist aesthetics of literary modernism were implicitly “ecological.” In order to make this argument I distinguish between contemporary and modernist ecological culture (both of which I differentiate in turn from ecological science); while the former is concerned primarily with the practical reform characteristic of what we now call “environmentalism,” the latter demanded an all-encompassing reimagination of the relationship between humanity and nature. “Modernist ecology,” as I call it, attempted to envision this change, which would be ontological or metaphysical rather than simply social, through thematically and formally experimental works of art. Its radical vision, suggestive in some ways of today’s “deep” ecology, repudiated modern accounts of nature as a congeries of inert objects to be manipulated by a sovereign subject, and instead foregrounded the chiasmic intertexture of the subject/object relationship. In aesthetic modernism we encounter not “objective” nature, but “nature-being” – a blank substratum beneath the solid contours of what philosopher Kate Soper calls “lay nature” – the revelation of which shatters historical constructions of nature and alone allows for radical alternatives. This essay looks specifically at modernist ecology as it appears in the works of W. B. Yeats, D. H. Lawrence, and Samuel Beckett, detailing their attempts to envision revolutionary new ecologies, but also their struggles with the limited capacity of esoteric modernist art to effect significant ecological change on a collective level.
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This work explores the idea of constitutional justice in Africa with a focus on constitutional interpretation in Ghana and Nigeria. The objective is to develop a theory of constitutional interpretation based upon a conception of law that allows the existing constitutions of Ghana and Nigeria to be construed by the courts as law in a manner that best serves the collective wellbeing of the people. The project involves an examination of both legal theory and substantive constitutional law. The theoretical argument will be applied to show how a proper understanding of the ideals of the rule of law and constitutionalism in Ghana and Nigeria necessitate the conclusion that socio-economic rights in those countries are constitutionally protected and judicially enforceable. The thesis argues that this conclusion follows from a general claim that constitutions should represent a ‘fundamental law’ and must be construed as an aspirational moral ideal for the common good of the people. The argument is essentially about the inherent character of ‘legality’ or the ‘rule of law.’ It weaves together ideas developed by Lon Fuller, Ronald Dworkin, T.R.S. Allan and David Dyzenhaus, as well as the strand of common law constitutionalism associated with Sir Edward Coke, to develop a moral sense of ‘law’ that transcends the confines of positive or explicit law while remaining inherently ‘legal’ as opposed to purely moral or political. What emerges is an unwritten fundamental law of reason located between pure morality or natural law on the one hand and strict, explicit, or positive law on the other. It is argued that this fundamental law is, or should be, the basis of constitutional interpretation, especially in transitional democracies like Ghana and Nigeria, and that it grounds constitutional protection for socio-economic rights. Equipped with this theory of law, courts in developing African countries like Ghana and Nigeria will be in a better position to contribute towards developing a real sense of constitutional justice for Africa.
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This project analyzes contemporary black diasporic writing in Canada, arguing that Dionne Brand, Austin Clarke and Tessa McWatt evince a unique form of double-consciousness in their writings. Their work transforms African-American double-consciousness by locating it simultaneously within both the black diaspora and the practice of Canadian multiculturalism. The objective of this project is to offer a critical framework for situating these writers within the legacy of both Black Atlantic and Canadian cultural production. These writers do not aim to resolve their double-consciousness but rather dwell within that contradictory doubleness and hyphenation, forcing nation and diaspora to contend with one another in a discomfiting and unsettling dialogue. These authors employ the absences of the black diaspora to imagine new forms of black cultural production, multicultural citizenship and national identity. Their works produce a grammar of diasporic double-consciousness that locates the absented origins of diaspora within Canada. Brand’s depiction of temporality and Clarke’s tracing of movement explore the continuities between nation and diaspora while re-membering neglected aspects of the history of black Canada, such as the life and death of Albert Johnson. McWatt extends this blackening of nation by depicting coalitions between diasporic, indigenous, raced and sexed subjects. These authors transform hegemonic Canadian narratives of nation by dwelling in the hyphen, while their evocation of memory, absence, trauma, and desire gives blackness new meaning and legitimacy.
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This dissertation examines novels that use terrorism to allegorize the threatened position of the literary author in contemporary culture. Allegory is a term that has been differently understood over time, but which has consistently been used by writers to articulate and construct their roles as authors. In the novels I look at, the terrorist challenge to authorship results in multiple deployments of allegory, each differently illustrating the way that allegory is used and authorship constructed in the contemporary American novel. Don DeLillo’s Mao II (1991), first puts terrorists and authors in an oppositional pairing. The terrorist’s ability to traffic in spectacle is presented as indicative of the author’s fading importance in contemporary culture and it is one way that terrorism allegorizes threats to authorship. In Philip Roth’s Operation Shylock (1993), the allegorical pairing is between the text of the novel and outside texts – newspaper reports, legal cases, etc. – that the novel references and adapts in order to bolster its own narrative authority. Richard Powers’s Plowing the Dark (1999) pairs the story of an imprisoned hostage, craving a single book, with employees of a tech firm who are creating interactive, virtual reality artworks. Focusing on the reader’s experience, Powers’s novel posits a form of authorship that the reader can take into consideration, but which does not seek to control the experience of the text. Finally, I look at two of Paul Auster’s twenty-first century novels, Travels in the Scriptorium (2007) and Man in the Dark (2008), to suggest that the relationship between representations of authors and terrorists changed after 9/11. Auster’s author-figures forward an ethics of authorship whereby novels can use narrative to buffer readers against the portrayal of violent acts in a culture that is suffused with traumatizing imagery.
Resumo:
There has been a significant increase in the incidence of musculoskeletal disorders (MSD) and the costs associated with these are predicted to increase as the popularity of computer use increases at home, school and work. Risk factors have been identified in the adult population but little is known about the risk factors for children and youth. Research has demonstrated that they are not immune to this risk and that they are self reporting the same pain as adults. The purpose of the study was to examine children’s postures while working at computer workstations under two conditions. One was at an ergonomically adjusted children’s workstation while the second was at an average adult workstation. A Polhemus Fastrak™ system was used to record the children’s postures and joint and segment angles were quantified. Results of the study showed that children reported more discomfort and effort at the adult workstation. Segment and joint angles showed significant differences through the upper limb at the adult workstation. Of significance was the strategy of shoulder abduction and flexion that the children used in order to place their hand on the mouse. Ulnar deviation was also greater at the adult workstation as was neck extension. All of these factors have been identified in the literature as increasing the risk for injury. A comparison of the children’s posture while playing at the children’s workstation verses the adult workstation, showed that the postural angles assumed by the children at an adult workstation exceeded the Occupational Safety and Health Association (OSHA) recommendations. Further investigation is needed to increase our knowledge of MSD in children as their potential for long term damage has yet to be determined.
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Julian Barnes, Pat Barker, and Hanif Kureishi are all canonical authors whose fictions are widely believed to reflect the cultural and political state of a nation that is post-war, post-imperial and post-modern. While much has been written on how Barker’s and Kureishi’s early works in particular respond to and intervene in the presiding political narrative of the 1980s – Thatcherism – treatment of how revenants of Thatcherism have shaped these writers’ works from 1990 on has remained cursory. Thatcherism is more than an obvious historical reference point for Barker, Barnes, and Kureishi; their works demonstrate a sophisticated understanding of how Thatcher’s reworkings of the repertoires of Englishness – a representational as well as political and cultural endeavour – persist beyond her time in office. Barnes, Barker, and Kureishi seem to have reached the same conclusion as political and cultural critics: Thatcher and Thatcherism have remade not only the contemporary political and cultural landscapes but also the electorate and consequently the English themselves. Tony Blair’s conception of the New Britain proved less than satisfactory because contemporary repertoires of Englishness repeat and rework historical and not incidentally imperial formulations of England and Englishness rather than envision civic and populist formulations of renewal. Barnes’s England, England and Arthur & George confront the discourse of inevitability that has come to be attached to contemporary formulations of both political and cultural Englishness – both in terms of its predictable demise and its belated celebration. Kureishi’s The Buddha of Suburbia and “The Body” speak to an alteration that has taken place in which historical Englishness and Thatcherism have become complementary rather than contrasting discourses. What Barker’s Border Crossing and Double Vision offer against this backdrop is a subtle interrogation of how renewal itself comes to be a presiding mode of cultural reflection that absorbs revolutionary possibility.
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The development of cost-effective and reliable methods for the synthesis and separation of asymmetric compounds is paramount in helping to meet society’s ever-growing demand for chiral small molecules. Of these methods, chiral heterogeneous supports are particularly appealing as they allow for the reuse of the chiral source. One such support, based on the synergy between chiral organic units and structurally stable inorganic silicon scaffolds are periodic mesoporous organosilicas (PMOs). In the work described herein, I examine some of the factors governing the transmission of chirality between chiral dopants and prochiral bulk phases in chiral PMO materials. In particular, the exploration of 1,1’-binaphthalene-bridged chiral dopants with a focus on the point of attachment into the materials. Moreover, the effects of ordering in the materials are examined and reveal that chirality transfer is more facile in materials with molecular-scale order then those containing amorphous walls. Secondly, the issues surrounding the synthesis and purification of aryl-triethoxysilanes as siloxane precursors are addressed. Both the introduction of a two-carbon linker and the direct attachment of allyl and mixed allyldiethoxysilane species are explored. This work demonstrates that allyldiethoxysilanes are ideal, in that they are stable enough to permit facile synthesis, while still being able to hydrolyze completely to produce well-ordered materials. Lastly, the production of new bulk phases for chiral PMO materials is examined by introducing new prochiral nitrogen-containing siloxane precursors. Biphenyldiamine and bipyridine-bridged siloxane precursors are readily synthesized on reasonable scales. Their use as the bulk siloxane precursor in the production of PMO materials however, is precluded by insufficient gelation and additional siloxane precursors are necessary for the production of ordered materials. In addition to the research detailed above that forms the body of this thesis, two short works are appended. The first details the production of polythiophene assemblies mediated through coordination nanospaces, while the second explores the production of N-heterocyclic carbene functionalized gold nanoparticles through ligand exchange.
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Flow, recharge and transport dynamics in fractured rock aquifers with low lying rock outcrops is a largely unexplored area of study in hydrogeology. The purpose of this thesis is to examine these topics in an agricultural area in Eastern Ontario. The study consists of a regional scale groundwater quality study, an infiltration experiment that considers bacteria transport from the ground surface to a well, and a numerical modelling study that tests the parameters that affect surface infiltration of a tracer from a rock outcrop to a deeper horizontal fracture. In the water quality study, approximately 65% of the samples contained total coliform, 16% contained E. coli, and 1% contained nitrate-N at greater than 5 mg/L. Occurrence of E. coli increased when considering seasonality, where wells were drilled on rock outcrops, and for shallow well intervals. Nitrate-N did not occur above the Guidelines for Canadian Drinking Water Quality (Health Canada, 2012) of 10 mg/L. Rapid arrival times were observed in the infiltration study for both the microspheres (30 minutes) and a dye tracer (45 minutes) in a well approximately 6.0 m in horizontal and 2.8 m in vertical distance from the tracer source. Transport velocities were approximately 38.9 m/day for the dye tracer and 115.2 m/day for the colloidal tracer. Results of the model runs indicate that overburden can provide an effective protective layer to transport in fractures, that high groundwater velocities occur in larger fracture apertures and higher gradients dilute tracer concentrations, and that lower groundwater velocities occur with smaller fracture apertures and lower gradients result in elevated tracer concentrations. Lower rainfall rates, larger fracture apertures, early tracer time, larger gradients, and lower water levels maintained unsaturated conditions for longer time periods such that tracer transport was delayed until saturated conditions were attained. The overall heterogeneity of this aquifer environment creates a source water protection conundrum where the water quality is generally good, while transport can occur very quickly in proximity to rock outcrops and in areas with limited overburden.