The use of Terrestrial Laser Scanning in characterizing active tectonic processes from postseismic slip to the long term growth of normal faults

This thesis investigates two main hypotheses regarding uncertainty in the measurement of paleoseismic offsets used to estimate fault activity and paleoearthquake magnitudes on normal faults: (1) That variations in fault geometry have a significant effect on throw-rates and fault offsets; and (2) that postseismic deformation can be a significant component of the total fault slip for moderate magnitude earthquakes. These hypotheses are tested using high resolution terrestrial laser scan datasets of normal fault topographic offsets and surface ruptures. The first hypothesis is addressed by studying the crustal scale Campo Felice active normal fault in the Central Apennines, Italy. Variation in throw-rate along strike since the last glacial maximum (15 ka ±3) is measured from an offset periglacial surface at two hundred and fifty sites using cross sectional data derived from a high resolution terrestrial laser scan (TLS) dataset. The measurements are used to create a detailed throw-rate profile. Field measurements of fault geometry (strike, dip and kinematic slip direction) are also gathered. Variation in fault throw-rate is found to correlate with fault strike. A study of weathered band thickness on the exposed Miocene limestone bedrock fault scarp, thought to have been created by single past slip events on the fault also appears to correlate with fault strike. A strain-rate profile is calculated using the throw-rate profile and the field measurements of kinematic slip. In contrast to throw-rate, strainrate is independant of changes in fault strike and dip. It is suggested that strain-rate in comparison to throw-rate provides a more robust measure of fault activity as it is unaffected by changes in fault geometry. The outcome of this study is that paleoseismic studies on active faults should take into account fault geometry before choosing sites which may have anomalously high or low paleoseismic offsets. Fault geometry introduces significant uncertainty into the estimation of inferred paleoearthquake magnitudes from paleoseismic offsets and hence seismic hazard analysis. The second hypothesis is addressed through the study of near-field postseismic deformation (surface rupture afterslip) following the 6th April 2009 6.3 Mw L’Aquila earthquake, created by slip on the Paganica normal fault in the Central Italian Apennines. A novel use of TLS technology allowed the postseismic deformation at four sites along the L’Aquila surface rupture to be measured between 8 – 126 days after the earthquake. Complimentary measurements of postseismic deformation at a fifth site using a robotic total station were combined with the TLS datasets to describe the along strike variation in postseismic deformation. The near-field postseismic deformation measured occurred mostly in the immediate hangingwall of the surface rupture and increased with decreasing rate over time. The postseismic deformation measured is comparable to theoretical and empirical models which have been used to describe afterslip for previous earthquakes. The magnitude of near-field postseismic deformation was up to 60% that of the coseismic offset in the near-field and suggests that postseismic deformation can form a significant component of paleoseismic offsets of moderate magnitude. Postseismic deformation was also found to be greatest above regions of the fault zone where a high coseismic slip gradient existed, suggesting that postseismic deformation occurs at the periphery of the coseismic slip patch within the fault zone. Regression relationships which relate surface offset to moment magnitude are populated by field observations of surface offsets where earthquake magnitude is known. These regression relationships are then used to infer paleoearthquake magnitudes from paleoseismic offsets. The field studies used to populate regression relationships do not routinely take into account the potential effects of fault geometry and significant postseismic slip. As a result paleoearthquake magnitudes inferred from such regression relationships are maybe over estimated. It is suggested that future regression relationships of surface offset and moment magnitude should factor in the effects of fault geometry and postseismic deformation in order to produce a relationship in which surface offset (both coseismic and postseismic) is described for a range of magnitudes and, where possible, any local effects of fault geometry are removed from the input dataset. The production of such a relationship will allow paleoseismologists to measure combined coseismic and postseismic offsets from field studies and to infer paleoearthquake magnitude with decreased uncertainty

Serial analysis of genes expressed in normal human glomerular mesangial cells

Advances in sequencing based genomics like the Human Genome Mapping Project (HGMP) have meant that the majority of the estimated human genes have been at least partially sequenced. The variation in expression of a set of essentially identical genes will provide information on the molecular basis of phenotype. Serial analysis of gene expression (SAGE) is based on the ability to assign an individual transcript to a ten base pair 'tag', and the technology facilitating rapid sampling of such tags. Glomerular mesangial cells (MC) are considered to play a major role in the development of renal disease and in vitro culturing of MC's has become a model system with which to study the molecular mechanisms of glomerular pathology. To this end, a SAGE project was undertaken to identify genes expressed in normal human mesangial cells (NHMC). Primary normal human mesangial cells were cultured for periods up to 96 hrs. A total of 46,219 tags were sampled (14,953 unique tags). Tags were mapped to 20,382 sequences. Of these 79% of tags mapped to characterised cDNAs, 16% tags mapped to ESTs. 5% of tags failed to match any database entry. The most abundant tags mapped to ribosomal genes or genes associated with the cytoskeleton. Represented in the top ten tags were the matricellular genes transgelin (1.2%), SPARC (1%) type IV collagen (0.5%) and fibronectin (0.53%), which support the notion that the MC is a producer and re-modeller of the glomerular extracellular matrix (ECM). The contractile nature of MC was apparent with the high abundance of contractile proteins like myosins and tropomyosins. Also apparent in the transcriptome were lineage specific isoforms of several genes, supporting the myoblastoid linage of MC. Comparing the transcriptomes of the MC to other libraries revealed a high correlation between cells in the same lineage as MC, such as astrocytes, smooth muscle cells and fibroblasts when compared to libraries sampled from heart, liver and various other unrelated cell lines. Understanding gene expression in the mesangial cell facilitates a greater understanding of its role in renal pathology

Countering small bribes: principles and good practice guidance for dealing with small bribes including facilitation payments

This guidance is part of a series of publications produced by Transparency International UK (TI-UK) providing advice on good practice in countering bribery and corruption. The aim of this guidance is to help companies to address the significant challenge of countering small bribes, including facilitation payments. It is also designed to be of assistance to regulators, law-makers, prosecuting agencies and professional advisers which may wish to refer to a Transparency International position when forming their own decisions. The guidance draws on Transparency International’s extensive experience in developing global anti-bribery practice for the private sector as well as the advice and practical experience of the project’s Expert Advisory Committee, and interviews with representatives of companies

Multimodality and Memory in the Mise en page of Guillaume de Machaut's Mass

Guillaume de Machaut’s mass survives in only five manuscripts, which all form part of the surprisingly homogeneous ‘complete works’ set of Machaut manuscripts. In this contribution, I argue that the details of mise en page in these manuscripts are reflective both of scribal memorial processes and multimodality in action: in this work where one of the major modes (image) is absent, the musical notation itself takes on an additional aesthetic role, that of visual beauty. In these manuscripts, the mass takes its place within the music section, surrounded there by lays, motets, virelais, and rondeaux, these surrounded (or preceded) by courtly ‘dits’ and lyrics not set to music. Four of these five manuscripts are illuminated, and all provide musical notation: all, therefore, are overtly multimodal. Despite the lavish illumination in the manuscripts, the mass is never adorned with a miniature, nor is it mentioned in Machaut’s ‘Prologue’ to his works. The aesthetic beauty of the mise en page of the mass, therefore, is derived from the musical notation, while the text-music setting shows a distinct divide between the two contrasting compositional techniques of the mass

Women’s experiences of receiving care for pelvic organ prolapse: a qualitative study

Background Pelvic organ prolapse is a common urogenital condition affecting 41–50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women’s needs, throughout their patient journey. This study explored women’s experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. Methods Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women’s experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. Results Three themes emerged relating to women’s experiences of a) Evaluating what is normal b) Hobson’s choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals’ preferences which were subtly reflected through the framing of the offer. Women’s embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women’s preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. Conclusions As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 μg mL–1, P =.223; 3.6 vs 3.5 μg mL–1, P =.569; 50.1 vs 46.8 μg mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival

Implementing pelvic floor muscle training for women with pelvic organ prolapse: a realist evaluation of different delivery models.

Background Pelvic Floor Muscle Training (PFMT) has been shown to be effective for pelvic organ prolapse in women, but its implementation in routine practice is challenging due to lack of adequate specialist staff. It is important to know if PFMT can be delivered by different staff skill mixes, what barriers and facilitators operate in different contexts, what strategies enable successful implementation and what are the underlying mechanisms of their action. PROPEL intervention was designed to maximise the delivery of effective PFMT in the UK NHS using different staff skill mixes. We conducted a realist evaluation (RE) of this implementation to understand what works, for whom, in what circumstances and why. Methods Informed by the Realist and RE-AIM frameworks, the study used a longitudinal, qualitative, multiple case study design. The study took place in five, purposively selected, diverse NHS sites across the UK and proceeded in three phases to identify, test and refine a theory of change. Data collection took place at 4 time points over an 18 month implementation period using focus groups and semi-structured interviews with a range of stakeholders including service leads/managers, senior practitioners, newly trained staff and women receiving care in the new service models. Data were analysed using thematic framework approach adapted to identify Context, Mechanism and Outcome (CMO) configurations of the RE. Results A heightened awareness of the service need among staff and management was a mechanism for change, particularly in areas where there was a shortage of skilled staff. In contrast, the most established specialist physiotherapist-delivered PFMT service activated feelings of role protection and compromised quality, which restricted the reach of PFMT through alternative models. Staff with some level of prior knowledge in women’s health and adequate organisational support were more comfortable and confident in new role. Implementation was seamless when PFMT delivery was incorporated in newly trained staff’s role and core work. Conclusion Roll-out of PFMT delivery through different staff skill mixes is possible when it is undertaken by clinicians with an interest in women’s health, and carefully implemented ensuring adequate levels of training and ongoing support from specialists, multi-disciplinary teams and management

A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines.

BACKGROUND: ENU-mutagenesis is a powerful technique to identify genes regulating mammalian development. To functionally annotate the distal region of mouse chromosome 4, we performed an ENU-mutagenesis screen using a balancer chromosome targeted to this region of the genome. RESULTS: We isolated 11 lethal lines that map to the region of chromosome 4 between D4Mit117 and D4Mit281. These lines form 10 complementation groups. The majority of lines die during embryonic development between E5.5 and E12.5 and display defects in gastrulation, cardiac development, and craniofacial development. One line displayed postnatal lethality and neurological defects, including ataxia and seizures. CONCLUSION: These eleven mutants allow us to query gene function within the distal region of mouse chromosome 4 and demonstrate that new mouse models of mammalian developmental defects can easily and quickly be generated and mapped with the use of ENU-mutagenesis in combination with balancer chromosomes. The low number of mutations isolated in this screen compared with other balancer chromosome screens indicates that the functions of genes in different regions of the genome vary widely