Rev Prof D. W. D. Shaw OBE (1928–2020)

In honour of the late Rev Prof D. W. D. Shaw, a founding member of the Editorial Board of Theology in Scotland, we are pleased to publish this tribute by Rev Prof George Newlands. This is a shortened version of George’s contribution to the Conference held at New College in 2018 to celebrate Bill’s 90th birthday

Studies in constructive theology

This submission centres on substantive issues of constructive theology, and particularly on interpreting the love of God. The focus is on the multi -layered impact of a Christology of divine love, developed through five monographs (I began to look at concepts of love as key to exegesis in theology in my Ph.D. thesis, published as EXEGESIS AND METHOD IN HILARY OF POITIERS, 1978).THEOLOGY OF THE LOVE OF GOD (1980) explores concepts of the love of God as the basic structuring element of Christian theology. In engagement with interpretations of love in the tradition, and with contemporary use of concepts of faith, hope and history, it is proposed that the nature of God as love shapes every aspect of theology. This is exemplified through analysis of the relationship between creation and redemption, understood as one dynamic movement, disrupting boundaries of redemption.IN GOD IN CHRISTIAN PERSPECTIVE (1994) the enterprise is developed further. An understanding of God as a multifaceted model draws on Christology and Trinity, faith and practice in community. God is personal, self -differentiated being, transcendent, yet also immanent in the created order as hidden divine presence. The core elements -faith and revelation, divine action and Christology -are reappraised in the light of current theological proposals. Doctrines interact in a web of connection to shape Christian practice. A Christian understanding retains the basic core of unconditional love, Christologically characterised. A contemporary concept of God draws upon these core elements, and upon a retrieval of the historical traditions from which they arise. It can be articulated in language intelligible to contemporary citizens, and its consequences spelled out within the complexity of contemporary cultures.Generosity and the Christian Future (1997) carries this thesis to a further stage through engagement with the emancipatory theologies, postmodernity, and political theory. The study re- imagines the framework of the divine love conceived as generosity. The need to be as alert to potential future as to past developments, and to relate doctrine to political theory and cultural issues, is grounded in theological -more precisely kenotic-Christological argument. Attention is paid to issues of human rights, violence, gender and the power structures of the churches themselves.JOHN AND DONALD BAILLIE TRANSATLANTIC THEOLOGY (2002), built on first access to the Baillie Papers, lies at the heart of this submission. I regard the work of the Baillies as seminal to the understanding, justification and revisioning of a progressive Christian theology. This is a theological biography of the Baillie brothers. It traces in detail the interaction of their theology within the cultures in Europe and America in which they worked - notably in the circle of the `critical realists.' It sheds light on the huge influence of the Baillies in Scotland. This tradition is a trajectory against the stream today. I judge it to offer significant resources, combining conceptual plasticity with distinctive direction, for the future.THE TRANSFORNTATIVE IMAGINATION -RETHINKING INTERCULTURAL THEOLOGY (2004). This comparative study of connections between theology and culture, through the arts, the sciences, political and human rights issues, shapes reflection on the mystery of God in a postfoundational frame. Reciprocity between ethical issues and questions of transcendence is explored. This yields a reconception of theological methodologies, in which theology, and paradoxically Christology, is seen as a catalyst rather than a trump card in interdisciplinary projects -exemplified through specific instances in the humanities, the sciences and in politics.The central theme of the divine love is spelled out in two shorter studies in less technical style. THE CHURCH OF GOD (1984) comments critically on traditions of church, ministry and sacraments in denominational cultures, stressing the Christological imperative to be an always outward looking church. MAKING CHRISTIAN DECISIONS (1985) assesses Christian input into specific ethical issues. I include also the jointly produced collections Studies in Scottish Church History (2000), BELIEVING IN THE TEXT (2004), EXPLORATIONS IN THEOLOGY 8 (1981), and FIFTY KEY CHRISTIAN THINKERS (2004), together with a selection of published articles. The submission documents a project with a distinctive accent on the love of God as Christological leitmotif. It conceives theology as a generous approach to the transcendence of God and the consequences of incarnation

Exegesis and method in Hilary of Poitiers

The purpose of the thesis is to analyse Hilary's interpretation of the Bible, particularly in his strictly exegetical works, in order to clarify the relationship betucen his exegetical method and his systematic theology as a whole.First the development of the commentary structure in the history of interpretation is traced, with particular reference "to matters of structure and interijretation relevant to Hilary's own work. There follows an analysis of the commentary on St. Matthew's Gospel, and of the central role of the interaction of literary structure and basic theological conception in the interpretation of the texts.Attention then turns to the Be Trinitate, in which the interplay of exegesis and theology in the rather different relationship arising from more strictly systematic theology is examined. This study then serves as a guide to consideration of the relationship in Hilary's exegesis of the Psalms.The results may be summarised as follows: beginning from the traditional western exegetical techniques in the work on 3t. Matthew, Hilary develops, with the aid of the theological concentration on the incarnation in the Be 'Trinitate, a greater versatility in the use of new techniques, some from the eastern tradition, the latest stages being exemplified in the work on the Psalms.After the assessment of the various stages of development Use other side if necessary. an attempt is made to relate the problem of exegesis and method in Hilary to similar problems in contemporary theology, and to indicate areas in which the use of patristic texts nay assist the development of solutions to modern problems

The regulation of mast cell growth and protease expression by cytokines

In this study the diversity of mast cell proteases and some of the factors regulating mast cell growth and protease expression were examined.Five proteases were isolated from mouse small intestinal mucosa and characterised in terms of their substrate specificities, substrate and inhibitor kinetics and immunohistochemical localisation. These studies revealed that the isolated proteases were all of mast cell origin and that they were chymotrypsin-like in their substrate specificities. The proteases were all identified as variants of mouse mast cell protease-1 which differed only in their carbohydrate moieties. Despite the fact that these enzymes shared a common core polypeptide they all differed significantly in the rate at which they hydrolysed low molecular weight synthetic substrates and in the rates at which they were inhibited by a,-proteinase inhibitor. A similar, but distinct protease was isolated from peritoneal cavity mast cells of mice. This enzyme, also a chvmase, had N-terminal sequence consistent with identification of the enzyme as mouse mast cell protease-4 which had previously only been identified by N-terminal sequence analysis of electro-blotted protein and from cDNA sequencing. This enzyme was not inhibited by, and actually degraded a]-proteinase inhibitor.Some of the factors which regulate mast cell growth, proliferation, survival and protease expression were examined in the rat. Stem cell factor (SCF) or cytokine-rich lymph node conditioned medium (LNCM) was administered to normal rats by intraperitoneal injection and the effects on a defined cell populations, the connective tissue mast cells (CTMC) of the peritoneal cavity were monitored. LNCM did not cause an increase in CTMC numbers but it did stimulate a switch in protease expression from rat mast cell protease I (RMCP I) alone to dual expression of both RMCP I and RMCP II. SCF alone caused a significant increase in CTMC numbers coupled with a decrease in RMCP I content and an increase in RMCP II content. Treatment with both LNCM and SCF together caused an even greater increase in both CTMC numbers and RMCP II expression than that seen with SCF alone. A second experiment was carried out where SCF was administered by daily intravenous injection for 14 days to both normal and parasitised rats and the effects of the treatment on CTMC and mucosal mast cell (MMC) populations was monitored. Intravenous SCF treatment resulted in a five-fold increase in peritoneal mast cell numbers with a concomitant decrease in RMCP I content. There was no significant expression of RMCP II in the CTMC of these animals.An alternative approach in examining the role of SCF in regulating mast cell populations w as the use of polyclonal antibodies raised against SCF to try and block SCF activity in both normal and parasitised rats. In normal rats, treatment with anti-SCF antibodies caused an approximately 50% decrease in the number of mast cells detected in the peritoneal cavity and totally ablated the MMCs from the small intestinal mucosa. In parasitised rats treated with anti-SCF antibodies, the mucosal mast cell hyperplasia associated with infection was significantly delayed in rats infected with Nippostrongvlus brasiliensis or Trichinella .spiralis and completely ablated in rats infected with Schistosoma mansoni. The depletion of mast cells from the intestinal mucosa was accompanied by a reduction in the tissue concentration of RMCP II. When anti-SCF antibodies were administered to rats which had already developed a mast cell hyperplasia following N. brasiliensis infection, there was again a significant depletion of both mast cells and RMCP II from the small intestine.A sensitive ELISA test was developed to measure soluble SCF in blood. This assay showed that circulating SCF levels were significantly increased by infection with both A. brasiliensis and '/'. spiralis. Taken together these results show that SCF and the cytokines in LNCM play an important role in the regulation of mast cell populations and their expression of proteases

John McIntyre and History

George Newlands takes us on a tour through McIntyre's writings on one of the central themes of his scholarship, the relationship between Christianity and history

"Travelling With Resilience: Essays for Alastair Haggart" edited by Elizabeth Templeton

Review of Elizabeth Templeton, ed., Travelling With Resilience: Essays for Alastair Haggart (Edinburgh: Scottish Episcopal Church, 2002

Examination of England’s New Medicine Service (NMS) of complex health care interventions in community pharmacy

Background: Community pharmacies are increasingly commissioned to deliver new, complex health interventions in response to the growing demands on family doctors and secondary health care services. Little is known about how these complex interventions are being accommodated and translated into the community pharmacy setting and whether their aims and objectives are realized in practice. The New Medicine Service (NMS) is a complex medicine management intervention that aims to support patients’ adherence to newly prescribed medicines for a long-term condition. Objective: This study explores the recent implementation of the NMS in community pharmacies across England. It also seeks to understand how the service is becoming manifest in practice and what lessons can be learned for future service implementation. Methods: Structured, organizational ethnographic observations and in situ workplace interviews with pharmacists and support staff were undertaken within 23 English community pharmacies. Additionally, one-toone, semi-structured interviews were carried out with 47 community pharmacists and 11 general practitioners (GPs). Observational and interview data were transcribed and analysed thematically and guided by Damschroder’s consolidated framework for implementation research. Results: The NMS workload had been implemented and absorbed into pharmacists’ daily routines alongside existing responsibilities with no extra resources and little evidence of reduction in other responsibilities. Pharmacists were pragmatic, simplifying, and adapting the NMS to facilitate its delivery and using discretion to circumvent perceived non-essential paperwork. Pharmacist understanding of the NMS was found to impact on what they believed should be achieved from the service. Despite pharmacists holding positive views about the value of the NMS, not all were convinced of its perceived benefits and necessity, with reports that many consultations did not identify any problems with the patients’ medicines. GPs were generally supportive of the initiative but were unaware of the service or potential benefits. Poorly developed existing pharmacist-GP relationships impeded implementation. Conclusions: This study identifies the multifaceted and complex processes involved in implementing a new community pharmacy service in England. Community pharmacy workflow, infrastructure, and public and professional relationships all affect NMS implementation. Greater prior engagement with the pharmacy workforce and GPs, robust piloting and a phased rollout together with ongoing support and updates, are potentials strategies to ensure future implementation of pharmacy services meet their intended aims in practice

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570