The Exodus Motif in the Gospel of Mark

This dissertation aims to demonstrate the prominent and multifaceted use of the exodus motif in Mark. Chapters 1 and 2 will examine the exodus motif in the beginning of the gospel, focusing on the opening citation and the wilderness setting in the early chapters. Here, it will be argued, the exodus is recapitulated in the life and ministry of Jesus. Chapters 3 and 4 will move to the middle of the gospel, exploring the exodus language at the heart of the transfiguration and Jesus’ journey along ‘the way’ towards Jerusalem. It will be shown that the exodus motif is inverted in this central section. This new exodus journey ends not in triumph but tragedy, not with conquest but a cross. Chapters 5 and 6 will examine the exodus motif at the end of the gospel, focusing on the Passover framework and the torn temple veil. Here, it will be maintained, the exodus is superseded by a greater redemptive act

Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life

Objectives: Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health-related quality of life (HrQoL) associated with rCDI hospitalisations. Patients and methods: A non-interventional study in 6 UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalised for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28-days (or death, if sooner); UK-specific reference costs were applied. HrQoL was assessed prospectively in a separate cohort of 30 patients hospitalised with CDI, who completed the EQ-5D-3L questionnaire during their illness. Results: The median total management cost (post-index) was £7,539 and £6,294 for rCDI and fCDI, respectively (cost difference, p=0.075); median length of stay (LOS) was 21 days and 15.5 days, respectively (p=0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£-1,873-£3,954). Subgroup analysis demonstrated the highest median costs (£8,542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital LOS, which accounted for >85% of costs in both groups. Mean EQ-5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ-VAS scores were 38% lower (47.82 and 77.3, respectively). Conclusions: CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real-world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

The Significance of Holy Land Pilgrimage for Anglican Clergy: An Anthropological Investigation.

This study aims to investigate the reactions of a group of Anglican clergy who visited the Holy land on pilgrimage in January 1995. The academic discipline is anthropological. The study employs qualitative methods of a multiple nature. Participant observation is the basis of the fieldwork. A symbolic interactionist approach forms the basis of the data analysis. A pilot study with a similar group twelve months previously laid the methodological basis for the multi-method enquiry. This was based further on my own experience over several years in leading pilgrimage parties to the Holy Land and other European pilgrimage sites. Particularly I had for twelve years led clergy parties of the sort which I accompanied in 1995. Participant observation and in-depth interviews with six main informants formed the basis of the study. Informal interviews provided further valuable data material. Further interviews afterwards at home with the main informants enabled me to gauge the ongoing impact of the pilgrimage on their lives and ministries. I review the anthropological literature on tourism, where relevant, and fully on pilgrimage. The seminal works of Victor Turner and his theories of communitas form a core discussion as the particular liminal/liminoid status of the clergy has special significance in relation to Turner's understanding of structure and anti-structure. The work of John Eade and Michael Sallnow is also central to the discussion of this thesis in their triad notion of person, place and text as underpinning the potency of the pilgrimage experience These ideas of communitas and the triad of person, place and text form substantive themes which are emically tested in the data analysis. Other themes in the data were mostly generated from the actual perceptions of the clergy pilgrims. The originality of this research is twofold. There is no previous methodological template for an ethnographic study of a group of pilgrims in any setting. As far as the Holy Land is concerned this is the first study of the impact of a pilgrimage tour there on individuals, and of clergy in particular. It also breaks new ground in being an ethnographic study of any aspect of clergy life

Relative demographic susceptibility does not explain the extinction chronology of Sahul's megafauna

The causes of Sahul's megafauna extinctions remain uncertain, although several interacting factors were likely responsible. To examine the relative support for hypotheses regarding plausible ecological mechanisms underlying these extinctions, we constructed the first stochastic, age-structured models for 13 extinct megafauna species from five functional/taxonomic groups, as well as 8 extant species within these groups for comparison. Perturbing specific demographic rates individually, we tested which species were more demographically susceptible to extinction, and then compared these relative sensitivities to the fossil-derived extinction chronology. Our models show that the macropodiformes were the least demographically susceptible to extinction, followed by carnivores, monotremes, vombatiform herbivores, and large birds. Five of the eight extant species were as or more susceptible than the extinct species. There was no clear relationship between extinction susceptibility and the extinction chronology for any perturbation scenario, while body mass and generation length explained much of the variation in relative risk. Our results reveal that the actual mechanisms leading to the observed extinction chronology were unlikely related to variation in demographic susceptibility per se, but were possibly driven instead by finer-scale variation in climate change and/or human prey choice and relative hunting success.Peer reviewe

Genomic investigation of clinically significant coagulase-negative staphylococci

Introduction. Coagulase-negative staphylococci have been recognized both as emerging pathogens and contaminants of clinical samples. High-resolution genomic investigation may provide insights into their clinical significance. Aims. To review the literature regarding coagulase-negative staphylococcal infection and the utility of genomic methods to aid diagnosis and management, and to identify promising areas for future research. Methodology. We searched Google Scholar with the terms ( Staphylococcus ) AND (sequencing OR (infection)). We prioritized papers that addressed coagulase-negative staphylococci, genomic analysis, or infection. Results. A number of studies have investigated specimen-related, phenotypic and genetic factors associated with colonization, infection and virulence, but diagnosis remains problematic. Conclusion. Genomic investigation provides insights into the genetic diversity and natural history of colonization and infection. Such information allows the development of new methodologies to identify and compare relatedness and predict antimicrobial resistance. Future clinical studies that employ suitable sampling frames coupled with the application of high-resolution whole-genome sequencing may aid the development of more discriminatory diagnostic approaches to coagulase-staphylococcal infection

Mortality risks associated with emergency admissions during weekends and public holidays: electronic health records study

Background: Higher mortality is associated with weekend hospital admission, but the contributions of varying illness severity and admission time to this ‘weekend effect’ remain unexplored. Methods: We analysed unselected emergency admissions to four Oxford University NHS hospitals, UK, January 2006-December 2014. The primary outcome was death within 30-days of admission (in/out of hospital), adjusted for multiple confounders in Cox models including or excluding test results. Findings: 257,596 individuals underwent 503,938 emergency admissions. 18,313 (4·8%) weekday and 6,070 (5·1%) weekend emergency admissions died within 30-days (p0.06). Interpretation: Adjusting for routine test results substantially reduced excess mortality associated with weekend/public holiday emergency admission. Adjusting for patient-level factors not available in our study could further reduce the residual excess mortality, which clustered around midday on Saturday/Sunday. Hospital workload was not associated with mortality. Together, these findings suggest that the ‘weekend effect’ arises from patient-level differences at admission rather than reduced hospital staffing or services

A Case of Treatment Resistance and Complications in a Patient with Stiff Person Syndrome and Cerebellar Ataxia

Background: Antibodies against glutamic acid decarboxylase (GAD) are associated with Stiff Person Syndrome (SPS). Case report: A 50-year-old woman presented with symptoms progressed over 9 years, resulting in a cerebellar ataxia and right upper limb tremor. Investigations revealed elevated serum and CSF anti-GAD antibody titres (98.6 and 53.4 μ/ml, respectively). Treatment included intravenous immunoglobulin and immunomodulation (infliximab and rituximab), improving her stiffness, but with no impact on the ataxia-related symptoms. Subsequent high-dose steroids led to diabetic ketoacidosis and unmasking of an insulin-dependent diabetes mellitus. Discussion: This case illustrates several key features: (1) the combined clinical picture of SPS and cerebellar ataxia is a rare phenotype associated with anti-GAD antibodies; (2) the cerebellar ataxia described was progressive and poorly responsive to immunomodulatory therapy; and (3) the potential for development of further autoimmune sequelae in response to immunosuppression, namely, the development of insulin-dependent diabetes in response to treatment with high-dose oral steroids