Failure mechanisms in sensitive volcanic soils in the Tauranga Region, New Zealand

Sensitive soils derived from weathered pyroclastic materials have contributed to major landslides in the Bay of Plenty. Sensitive soils have a high ratio of peak to remoulded undrained strength. While it is known that (a) sensitive soils flow once failed, causing long runout distances, and (b) these failures often occur following heavy rainfall, the mechanisms that lead to failure are less understood. The aim of this thesis is to determine static and cyclic failure mechanisms of sensitive soils sampled from the failure scarps of two recent landslides in the Tauranga Region. Revelations about how these soils fail will allow slope stability models to more accurately capture geomechanical behaviour. Recent publications on sensitive soils derived from glacial till materials have indicated that these soils are brittle materials displaying undrained strain softening behaviour, where deviator stress drops significantly following peak stress. Failure is governed by rate dependant, excess pore pressure gradients accumulating during undrained, consolidated triaxial compression (Gylland et al. 2013c; 2014; Thakur et al. 2014). These publications provided a methodological backbone for this thesis. Field methods included geomorphological and stratigraphic site characterisation, and sampling of extra sensitive soil suspected of contributing to failure. Laboratory methods included geotechnical tests (Atterberg Limits, moisture content, bulk and particle density, particle size distribution, and static and cyclic undrained, consolidated triaxial tests). Static triaxial testing was undertaken at a high compression rate of 0.5mm/min to model rapid undrained during slope failure. Different combinations of average and cyclic shear stresses allowed replication of Anderson’s (2015) cyclic contour plot. Shear zone microstructure of failed triaxial samples was analysed using thin section and micro-CT techniques. Two coastal cliff landslide sites were characterised and sampled: (1) a significant landslide at Bramley Drive, Omokoroa, which initially occurred in 1979, with reactivations in 2011 and 2012, and (2) a landslide on the south side of Matua Peninsula, which occurred in 2012. The bowl-shaped landslide crater at Bramley Drive and long runout component of sensitive material are likely due to failure within an over-thickened sequence pyroclastic material (Pahoia Tephras), which initially accumulated in a paleovalley. At Matua, the failure surface was long, slightly rotational, and comprised a sequence of variable sandy lenses and silty clays. Landslide debris comprised remoulded sensitive material underlying intact overlying blocks, indicating failure of a sensitive soil layer at depth. Material sampled at Omokoroa (OM1) was an extra sensitive (St = 15 ± 3) silty CLAY, 19 m from top of profile within Pahoia Tephras. Material at Matua (M1) was an extra sensitive (St = 10 ± 1) silty CLAY, 16 m from the top, within the Matua Subgroup. Clay mineralogy of these soils is known to be various morphologies of hydrated halloysite. Samples from both sites have dominant clay fractions (OM1: clay: 62.6%, silt: 37.3%, sand: 0.1%, M1: clay: 40.1%, silt: 22.3 %, sand: 37.6%). High porosity (OM1: 70% M1:66%), void ratio (OM1: 2.3 M1: 1.8), and moisture content (OM1: 72%, M1: 64%), together with low wet and dry bulk densities (wet b.d: OM1:1320 kgm-3, M1: 1690 kgm-3, dry b.d: OM1: 760 kgm-3, M1: 980 kgm-3), are in keeping with previously published values of halloysite-rich clays derived from pyroclastic material. Atterberg Limits are high for both materials (Liquid limit: OM1: 66 M1: 52, Plastic limit: OM1: 41, M1: 37, Plasticity index: OM1: 25 M1: 15, Liquidity index: OM1: 2.9 M1: 1.8). M1 and OM1 both plot below the A-line in the range of high compressibility silts (MH). M1 and OM1 both have low activity, reflecting the hydrated halloysite composition (OM1: 0.4, M1: 0.4). Static undrained, consolidated triaxial tests show that failure occurs at less than or near to 5% strain for all tests, indicating brittle failure. Two main types of failure mechanisms were recognised from triaxial results. Post failure, type A was characterised by significant strain softening, contractive, left trending p’q’ stress paths, and a rise in global pore pressure after failure. Type B response post-peak deviator stress showed minor to no strain softening, dilative, right trending p’q’ paths, and a drop in global pore water pressure. In general, test rate, confining pressure and material affect the type of failure: higher compression rates and confining pressures correlate with type A failure, whereas the opposite is true for type B failure. Failure modes observed in failed triaxial samples were either wedge or shear, with the exception of M1a (tested at 75 kPa confining pressure) which failed by barrel deformation. Strain softening increased with effective confining pressure (R2= 0.58). Average effective cohesion and friction remain essentially consistent between peak and residual states (OM1: c’f = 26, c’r = 24, φ’f = 31, φ’r=26, M1: c’f = 17, c’r = 17 φ’f = 32, φ’r = 29). Thin sections captured shear zones tested at 240 kPa and 340 kPa (OM1), and 150 kPa and 255 kPa (M1) confining stress. Riedel shears (R and R’) and P shears were observed in all thin sections. Evidence for progressive failure, most notably changes in the abundance and spacing of shears along the same shear zone, was found in both materials. Clay mineral realignment was observed in shear zones. Micro-CT results showed clay matrix material to be denser in shear zones, implying localised contraction of microstructure. I infer that type A failure mechanism is comparable to sensitive soils that Gylland et al. (2013c; 2014) studied. During compression, pore pressure does not have time to dissipate, leading to excess pore pressure gradients, which initiate brittle failure where a release of potential energy results in R shear fractures and R’ fractures which become linked by P shears. Microstructural collapse within these fractures induces further excess pore pressure, liquefying material in shear zones, and resulting in a loss of material resistance as evidenced by the strain softening behaviour observed. Realigned material in shear zones provides a pathway for excess pore pressure to dissipate, finally registering as a rise in pore pressure in the post-peak region. Integrity of cohesive bonds and asperity interaction is preserved during shearing, resulting in little to reduction of c’ and φ’. For type B failure, lower confining pressures and/or test rates mean that pore pressure has ample time to dissipate during compression, so that when the critical state line in p’q’ diagrams is reached, grains interlock, causing pore pressures to drop (dilation). Boulanger & Idriss (2007) conclude that for sensitive materials, it is difficult to assess the strain or ground displacement that will reduce the clay from peak to residual strength during cyclic loading. In this study, I utilised a new geotechnical tool, a cyclic contour plot (Anderson, 2015), that predicts the cycles to failure, and the average shear strain and cyclic shear strain at failure, for combinations of applied average and cyclic shear stresses. Seven samples were tested at different combinations of average and cyclic shear stresses. Tests with high average and low cyclic shear stress applications resulted in progressive, positive strain accumulation. Tests with no average but high cyclic shear stresses resulted in progressive accumulation of strain in both positive and negative directions. In comparison to Drammen Clay (Anderson, 2015), in general, for the same application of average and cyclic shear stress, failure occurs after a lesser number of cycles, but both average and cyclic strain accumulation is lower. Although limited microstructural evidence was analysed, observations tests show similar mechanisms as described above are responsible for failure under cyclic stresses; post-failure strain softening occurs, and excess pore pressure increases. One micro-CT sample of an entire failed sample tested at high (60 kPa) cyclic shear stress and zero average shear stress shows intense contraction in the shear zone. It is likely that following heavy rainfall events, excess pore pressure gradients develop in sensitive material at Bramley Drive and Matua, resulting in localised fracture development. Collapse of the disturbed sensitive soil in developing shear zones releases additional pore water, enhancing pore water pressure gradients and leading to progressive fracture. Ultimately, breakdown of the sensitive material results in liquefaction along a macroscopic failure surface and rafting away overlying material

New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases

Dried blood spots (DBSs) biomarkers are convenient for monitoring for specific lysosomal storage diseases (LSDs), but they could have relevance for other LSDs. To determine the specificity and utility of glycosphingolipidoses biomarkers against other LSDs, we applied a multiplexed lipid liquid chromatography tandem mass spectrometry assay to a DBS cohort of healthy controls (n = 10) and Gaucher (n = 4), Fabry (n = 10), Pompe (n = 2), mucopolysaccharidosis types I–VI (n = 52), and Niemann–Pick disease type C (NPC) (n = 5) patients. We observed no complete disease specificity for any of the markers tested. However, comparison among the different LSDs highlighted new applications and perspectives of the existing biomarkers. We observed elevations in glucosylceramide isoforms in the NPC and Gaucher patients relative to the controls. In NPC, there was a greater proportion of C24 isoforms, giving a specificity of 96–97% for NPC, higher than 92% for the NPC biomarker N-palmitoyl-O-phosphocholineserine ratio to lyso-sphingomyelin. We also observed significantly elevated levels of lyso-dihexosylceramide in Gaucher and Fabry disease as well as elevated lyso-globotriaosylceramide (Lyso-Gb3) in Gaucher disease and the neuronopathic forms of Mucopolysaccharidoses. In conclusion, DBS glucosylceramide isoform profiling has increased the specificity for the detection of NPC, thereby improving diagnostic accuracy. Low levels of lyso-lipids can be observed in other LSDs, which may have implications in their disease pathogenesis

A pilot evaluation of simulation-based interprofessional education for occupational therapy, speech pathology and dietetic students: improvements in attitudes and confidence

© 2019, © 2019 Taylor & Francis Group, LLC. Many higher education institutions struggle to provide interprofessional practice opportunities for their pre-licensure students due to demanding workloads, difficulties with timetabling, and problems with sourcing suitable placements that provide appropriate practice opportunities. A series of complex unfolding video-based simulation scenarios involving a patient who had experienced a stroke was utilized as a case study for a three-hour interprofessional practice workshop. 69 occupational therapy (OT), speech pathology (SP) and dietetics (DT) students participated in a mixed-methods study comparing interprofessional attitudes before and after the workshop. Attitudes toward interprofessional practice improved pre- vs. post-workshop and overall. Students were highly satisfied with the workshops contribution toward learning, although OT and SP students were more satisfied than DT students. Focus groups confirmed students liked the format and structure of the workshop, suggested that students better understood the role of other professions and improved role clarification, increased their confidence to practice in interprofessional practice settings, but noted the experience could have been improved with the incorporation of nursing and smaller groups to better facilitate participation. There is widespread support for implementing interprofessional education (IPE) in the health sciences, yet widespread implementation is not yet a reality. This research suggests that a simulation-based, three-hour IPE workshop can have an immediate benefit on confidence and attitudes toward interprofessional practice for allied health students

Cerebrospinal fluid neurofilament light chain levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment

Classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is caused by a deficiency of tripeptidyl-peptidase-1. In 2017, the first CLN2 enzyme replacement therapy (ERT) cerliponase alfa (Brineura) was approved by the FDA and EMA. The CLN2 disease clinical rating scale (CLN2 CRS) was developed to monitor loss of motor function, language and vision as well as frequency of generalised tonic clonic seizures. Using CLN2 CRS in an open label clinical trial it was shown that Brineura slowed down the progression of CLN2 symptoms. Neurofilament light chain (NfL) is a protein highly expressed in myelinated axons. An increase of cerebrospinal fluid (CSF) and blood NfL is found in a variety of neuroinflammatory, neurodegenerative, traumatic, and cerebrovascular diseases. We analysed CSF NfL in CLN2 patients treated with Brineura to establish whether it can be used as a possible biomarker of response to therapy. Newly diagnosed patients had CSF samples collected and analysed at first treatment dose and up to 12 weeks post-treatment to look at acute changes. Patients on a compassionate use programme who were already receiving ERT for approximately 1yr had CSF samples collected and NfL analysed over the following 1.3 years (2.3 years post-initiation of ERT) to look at long-term changes. All newly diagnosed patients we investigated with classical late infantile phenotype had high NfL levels >2000 pg/ml at start of treatment. No significant change was observed in NfL up to 12 weeks post-treatment. After one year of ERT, two out of six patients still had high NfL levels, but all patients showed a continued decrease, and all had low NfL levels after two years on ERT. NfL levels appear to correspond and predict improved clinical status of patients on ERT and could be useful as a biomarker to monitor neurodegeneration and verify disease modification in CLN2 patients on ERT

Niemann–Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders

AIM: Using Niemann-Pick type C disease (NPC) as a paradigm, we aimed to improve biomarker discovery in patients with neurometabolic disorders. METHOD: Using a multiplexed liquid chromatography tandem mass spectrometry dried bloodspot assay, we developed a selective intelligent biomarker panel to monitor known biomarkers N-palmitoyl-O-phosphocholineserine and 3β,5α,6β-trihydroxy-cholanoyl-glycine as well as compounds predicted to be affected in NPC pathology. We applied this panel to a clinically relevant paediatric patient cohort (n = 75; 35 males, 40 females; mean age 7 years 6 months, range 4 days-19 years 8 months) presenting with neurodevelopmental and/or neurodegenerative pathology, similar to that observed in NPC. RESULTS: The panel had a far superior performance compared with individual biomarkers. Namely, NPC-related established biomarkers used individually had 91% to 97% specificity but the combined panel had 100% specificity. Moreover, multivariate analysis revealed long-chain isoforms of glucosylceramide were elevated and very specific for patients with NPC. INTERPRETATION: Despite advancements in next-generation sequencing and precision medicine, neurological non-enzymatic disorders remain difficult to diagnose and lack robust biomarkers or routine functional testing for genetic variants of unknown significance. Biomarker panels may have better diagnostic accuracy than individual biomarkers in neurometabolic disorders, hence they can facilitate more prompt disease identification and implementation of emerging targeted, disease-specific therapies

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Convicts and coolies : rethinking indentured labour in the nineteenth century

This article seeks to shift the frame of analysis within which discussions of Indian indentured migration take place. It argues that colonial discourses and practices of indenture are best understood not with regard to the common historiographical framework of whether it was 'a new system of slavery', but in the context of colonial innovations in incarceration and confinement. The article shows how Indian experiences of and knowledge about transportation overseas to penal settlements informed in important ways both their own understandings and representations of migration and the colonial practices associated with the recruitment of indentured labour. In detailing the connections between two supposedly different labour regimes, it thus brings a further layer of complexity to debates around their supposed distinctions

The efficacy of behavioural activation treatment for co-occurring depression and substance use disorder (the activate study): a randomized controlled trial

Background Epidemiological studies suggest that compared with the general population, mood disorders are up to 4.7 times more prevalent in substance dependent samples. Comorbid substance use disorder (SUD) and depression has been associated with a more severe and protracted illness course and poorer treatment outcomes. Despite this, the development and assessment of behavioural interventions for treating depression among individuals with SUDs have received little empirical attention. Behavioural Activation Treatment for Depression (BATD-R) is an empirically supported treatment for depression that has shown some efficacy among substance users. This paper describes the study protocol of a parallel, single blind, randomised controlled trial to determine the efficacy and feasibility of a modified version of the BATD-R (Activate) in reducing symptoms of depression and substance dependence among individuals in residential rehabilitation (RR) and opioid substitution therapy (OST). Methods/design A sample of approximately 200 individuals with depressive symptomatology in treatment for SUD will be recruited from RR and OST services in New South Wales, Australia. Dynamic random allocation following minimisation methodology will be used to assign participants to one of two groups. The control group will receive treatment as usual (TAU), which will be the model of care provided in accordance with standard practice at participating RR and OST services. The intervention group will receive Activate, comprising 10 individual 60-min therapy sessions with a psychologist employed on the research team, in addition to TAU. Data collection will occur at baseline (pre-intervention), and 3-months and 12-months post baseline. Discussion The association between depression and substance dependence has been well documented, yet practical and effective treatments are scarce. The findings of the present study will contribute significantly to understanding the types of programs that are effective in treating this comorbidity. Trial registration This trial is registered with the Australian and New Zealand Clinical Trials registry, ACTRN12613000876796. Registered on 7 August, 2013. Electronic supplementary material The online version of this article (doi:10.1186/s12888-016-0943-1) contains supplementary material, which is available to authorized users

Factors that impact the upgrading of atypical ductal hyperplasia

PURPOSEThe purpose of this study was to identify the factors that may have an impact on upgrading atypical ductal hyperplasia (ADH) lesions to malignancy. MATERIALS AND METHODSBetween February 1999 and December 2010, the records of 150 ADH lesions that had been biopsied were retrospectively reviewed. The biopsy types included 11-gauge stereotactic vacuum-assisted biopsy (SVAB) (n=102) and ultrasonography (US)-guided 14-gauge automated biopsy (n=48). The patients were divided into two groups: those who had cancer in the ™nal pathology and those who did not. Variables associated with underestimation of ADH lesions were compared between the groups. RESULTSThe underestimation rates according to the biopsy types were 41.7% (20/48) for the US-guided 14-gauge automated biopsy and 20.6% (21/102) for the 11-gauge SVAB (P = 0.007). The rate of underestimation was signi™cantly higher in lesions greater than 7 mm than it was in smaller lesions, with both US-guided 14-gauge automated biopsy and 11-gauge SVAB (P = 0.024 and P = 0.042, respectively). The rate of underestimation was signi™cantly higher with the 11-gauge SVAB (P = 0.025) in lesions that were suspicious (R4) and highly suggestive of malignancy (R5) than in those that were probably benign (R3). CONCLUSIONThe underestimation rate in ADH lesions was signi™cantly higher with US-guided 14-gauge automated biopsy compared to the 11-gauge SVAB. The underestimation rate was also signi™cantly higher in lesions greater than 7 mm regardless of the biopsy type, and in lesions biopsied usi ng SVAB that were regarded as suspicious (R4) or highly suggestive of malignancy (R5) on imaging

Monitoring and managing lifestyle behaviours using wearable activity trackers: a mixed methods study of views from the Huntington's disease community

Background: There are early indications that lifestyle behaviors, specifically physical activity and sleep, may be associated with the onset and progression of Huntington disease (HD). Wearable activity trackers offer an exciting opportunity to collect long-term activity data to further investigate the role of lifestyle, physical activity, and sleep in disease modification. Given how wearable devices rely on user acceptance and long-term adoption, it is important to understand users’ perspectives on how acceptable any device might be and how users might engage over the longer term. Objective: This study aimed to explore the perceptions, motivators, and potential barriers relating to the adoption of wearable activity trackers by people with HD for monitoring and managing their lifestyle and sleep. This information intended to guide the selection of wearable activity trackers for use in a longitudinal observational clinical study. Methods: We conducted a mixed methods study; this allowed us to draw on the potential strengths of both quantitative and qualitative methods. Opportunistic participant recruitment occurred at 4 Huntington’s Disease Association meetings, including 1 international meeting and 3 United Kingdom–based regional meetings. Individuals with HD, their family members, and carers were invited to complete a user acceptance questionnaire and participate in a focus group discussion. The questionnaire consisted of 35 items across 8 domains using a 0 to 4 Likert scale, along with some additional demographic questions. Average questionnaire responses were recorded as positive (score>2.5), negative (score<1.5), or neutral (score between 1.5 and 2.5) opinions for each domain. Differences owing to demographics were explored using the Kruskal-Wallis and Wilcoxon rank sum tests. Focus group discussions (conducted in English) were driven by a topic guide, a vignette scenario, and an item ranking exercise. The discussions were audio recorded and then analyzed using thematic analysis. Results: A total of 105 completed questionnaires were analyzed (47 people with HD and 58 family members or carers). All sections of the questionnaire produced median scores >2.5, indicating a tendency toward positive opinions on wearable activity trackers, such as the devices being advantageous, easy and enjoyable to use, and compatible with lifestyle and users being able to understand the information from trackers and willing to wear them. People with HD reported a more positive attitude toward wearable activity trackers than their family members or caregivers (P=.02). A total of 15 participants participated in 3 focus groups. Device compatibility and accuracy, data security, impact on relationships, and the ability to monitor and self-manage lifestyle behaviors have emerged as important considerations in device use and user preferences