THE IMPACT OF THE BASEL III CAPITAL REQUIREMENTS ON THE PROFITABILITY AND LENDING BEHAVIORS OF GLOBAL SYSTEMICALLY IMPORTANT BANKS

The global financial crisis prompted a period of widespread regulatory changes geared towards creating a safer financial system. The Basel III regulation emerged post-crisis and adjusted the minimum capital requirements for banks, attempting to ensure that they would be better equipped to absorb losses in the case of the next potential crisis. Advocates of this regulation believe that our financial system is far safer when these higher capital requirements are in place, and some advocates believe these requirements should be even higher. On the other hand, critics of this regulation argue that as a result of these requirements, banks profit less and their lending behaviors are impacted negatively. The research question of this thesis was formed as a response to these critics and asks: What effect do the Basel III capital requirements have on bank profitability and lending behavior. This thesis uses a regression analysis to determine whether these capital requirements have had an impact on the profitability and lending behaviors of global systemically important banks.Bachelor of Scienc

Spatial considerations during cryopreservation of a large volume sample

AbstractThere have been relatively few studies on the implications of the physical conditions experienced by cells during large volume (litres) cryopreservation – most studies have focused on the problem of cryopreservation of smaller volumes, typically up to 2 ml.This study explores the effects of ice growth by progressive solidification, generally seen during larger scale cryopreservation, on encapsulated liver hepatocyte spheroids, and it develops a method to reliably sample different regions across the frozen cores of samples experiencing progressive solidification.These issues are examined in the context of a Bioartificial Liver Device which requires cryopreservation of a 2 L volume in a strict cylindrical geometry for optimal clinical delivery. Progressive solidification cannot be avoided in this arrangement. In such a system optimal cryoprotectant concentrations and cooling rates are known. However, applying these parameters to a large volume is challenging due to the thermal mass and subsequent thermal lag. The specific impact of this to the cryopreservation outcome is required.Under conditions of progressive solidification, the spatial location of Encapsulated Liver Spheroids had a strong impact on post-thaw recovery. Cells in areas first and last to solidify demonstrated significantly impaired post-thaw function, whereas areas solidifying through the majority of the process exhibited higher post-thaw outcome. It was also found that samples where the ice thawed more rapidly had greater post-thaw viability 24 h post-thaw (75.7 ± 3.9% and 62.0 ± 7.2% respectively).These findings have implications for the cryopreservation of large volumes with a rigid shape and for the cryopreservation of a Bioartificial Liver Device

Robust automatic hexahedral cartilage meshing framework enables population-based computational studies of the knee

Osteoarthritis of the knee is increasingly prevalent as our population ages, representing an increasing financial burden, and severely impacting quality of life. The invasiveness of in vivo procedures and the high cost of cadaveric studies has left computational tools uniquely suited to study knee biomechanics. Developments in deep learning have great potential for efficiently generating large-scale datasets to enable researchers to perform population-sized investigations, but the time and effort associated with producing robust hexahedral meshes has been a limiting factor in expanding finite element studies to encompass a population. Here we developed a fully automated pipeline capable of taking magnetic resonance knee images and producing a working finite element simulation. We trained an encoder-decoder convolutional neural network to perform semantic image segmentation on the Imorphics dataset provided through the Osteoarthritis Initiative. The Imorphics dataset contained 176 image sequences with varying levels of cartilage degradation. Starting from an open-source swept-extrusion meshing algorithm, we further developed this algorithm until it could produce high quality meshes for every sequence and we applied a template-mapping procedure to automatically place soft-tissue attachment points. The meshing algorithm produced simulation-ready meshes for all 176 sequences, regardless of the use of provided (manually reconstructed) or predicted (automatically generated) segmentation labels. The average time to mesh all bones and cartilage tissues was less than 2 min per knee on an AMD Ryzen 5600X processor, using a parallel pool of three workers for bone meshing, followed by a pool of four workers meshing the four cartilage tissues. Of the 176 sequences with provided segmentation labels, 86% of the resulting meshes completed a simulated flexion-extension activity. We used a reserved testing dataset of 28 sequences unseen during network training to produce simulations derived from predicted labels. We compared tibiofemoral contact mechanics between manual and automated reconstructions for the 24 pairs of successful finite element simulations from this set, resulting in mean root-mean-squared differences under 20% of their respective min-max norms. In combination with further advancements in deep learning, this framework represents a feasible pipeline to produce population sized finite element studies of the natural knee from subject-specific models

Emerging Gene-Editing Modalities for Osteoarthritis

Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments

Limited validity of the Hospital Anxiety and Depression Scale (HADS) in dementia: evidence from a confirmatory factor analysis

OBJECTIVES: The Hospital Anxiety and Depression Scale (HADS) is a well-validated, self-report measure of both anxiety and depression. It is frequently used with people with dementia. However, its structural validity has never been examined in this population. The current study used confirmatory factor analysis (CFA) to assess this. METHODS: Baseline data from two intervention studies for people with mild to moderate dementia were combined (N = 268). CFA was used to test whether a one, two or three factor structure best fit the data. Indices of model misspecification were examined to test for poor quality items, and models re-specified accordingly. Finally, measurement invariance across gender and different levels of cognitive impairment was assessed. RESULTS: A one-factor structure did not fit the data. Two and three factor structures fitted the data equally well. Model fit was improved by removal of two items. Measurement invariance was adequate across gender, but poor across groups with differing levels of cognitive impairment. CONCLUSION: The HADS is acceptable and feasible but difficult to interpret in a dementia population. We suggest that it should be interpreted as measuring two separate factors of anxiety and depression and not one 'distress' factor. However, two items may need to be removed, affecting cut-off scores. Poor measurement invariance means the HADS may not be a good tool for measuring differences in anxiety and depression between those with mild and those with moderate cognitive impairment

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation

ATRX dysfunction Induces replication defects in primary mouse cells

The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells

Challenges, solutions and future directions in the evaluation of service innovations in health care and public health

HeadlineEvaluating service innovations in health care and public health requires flexibility, collaboration and pragmatism; this collection identifies robust, innovative and mixed methods to inform such evaluations.This is the final version of the article. It first appeared from the National Institute for Helath Research via http://dx.doi.org/10.3310/hsdr0416

Long-term clinical and cost-effectiveness of collaborative care (versus usual care) for people with mental-physical multimorbidity : a cluster-randomised trial.

Background Collaborative care can support the treatment of depression in people with long-term conditions, but long-term benefits and costs are unknown. Aims To explore the long-term (24-month) effectiveness and cost-effectiveness of collaborative care in people with mental-physical multimorbidity. Method A cluster randomised trial compared collaborative care (integrated physical and mental healthcare) with usual care for depression alongside diabetes and/or coronary heart disease. Depression symptoms were measured by the symptom checklist-depression scale (SCL-D13). The economic evaluation was from the perspective of the English National Health Service. Results 191 participants were allocated to collaborative care and 196 to usual care. At 24 months, the mean SCL-D13 score was 0.27 (95% CI, −0.48 to −0.06) lower in the collaborative care group alongside a gain of 0.14 (95% CI, 0.06-0.21) quality-adjusted life-years (QALYs). The cost per QALY gained was £13 069. Conclusions In the long term, collaborative care reduces depression and is potentially cost-effective at internationally accepted willingness-to-pay thresholds

Changes in quality of life (QoL) and other patient-reported outcome measures (PROMs) in living-donor and deceased-donor kidney transplant recipients and those awaiting transplantation in the UK ATTOM programme: a longitudinal cohort questionnaire survey with additional qualitative interviews.

OBJECTIVE: To examine quality of life (QoL) and other patient-reported outcome measures (PROMs) in kidney transplant recipients and those awaiting transplantation. DESIGN: Longitudinal cohort questionnaire surveys and qualitative semi-structured interviews using thematic analysis with a pragmatic approach. SETTING: Completion of generic and disease-specific PROMs at two time points, and telephone interviews with participants UK-wide. PARTICIPANTS: 101 incident deceased-donor (DD) and 94 incident living-donor (LD) kidney transplant recipients, together with 165 patients on the waiting list (WL) from 18 UK centres recruited to the Access to Transplantation and Transplant Outcome Measures (ATTOM) programme completed PROMs at recruitment (November 2011 to March 2013) and 1 year follow-up. Forty-one of the 165 patients on the WL received a DD transplant and 26 received a LD transplant during the study period, completing PROMs initially as patients on the WL, and again 1 year post-transplant. A subsample of 10 LD and 10 DD recipients participated in qualitative semi-structured interviews. RESULTS: LD recipients were younger, had more educational qualifications and more often received a transplant before dialysis. Controlling for these and other factors, cross-sectional analyses at 12 months post-transplant suggested better QoL, renal-dependent QoL and treatment satisfaction for LD than DD recipients. Patients on the WL reported worse outcomes compared with both transplant groups. However, longitudinal analyses (controlling for pre-transplant differences) showed that LD and DD recipients reported similarly improved health status and renal-dependent QoL (p<0.01) pre-transplant to post-transplant. Patients on the WL had worsened health status but no change in QoL. Qualitative analyses revealed transplant recipients' expectations influenced their recovery and satisfaction with transplant. CONCLUSIONS: While cross-sectional analyses suggested LD kidney transplantation leads to better QoL and treatment satisfaction, longitudinal assessment showed similar QoL improvements in PROMs for both transplant groups, with better outcomes than for those still wait-listed. Regardless of transplant type, clinicians need to be aware that managing expectations is important for facilitating patients' adjustment post-transplant