The ‘Experience of Grace’ in the Theologies of Karl Rahner and Bernard Lonergan

Thesis advisor: Frederick LawrenceThe first chapter begins by delineating Lonergan’s philosophy of development. It then applies this philosophy to a range of literature on grace and discerns, in the historical data, a basic line of intellectual progress. For this reason, this chapter implements a genetic method. More specifically, the chapter proposes an explanatory framework for understanding the contemporary transposition of scholastic metaphysics. Special attention is placed on the notion of grace as experience in relation to the evolution of theology as a science. The first chapter implements a genetic method to chart the developments in the history of the theology of grace. The last section of that chapter sketches the basic contours of a development that enabled a transposition from the second to the third stage of meaning—a development that made possible a description of grace in terms of consciousness. The second chapter addresses the question of grace and consciousness in the context of Lonergan’s thought. In this chapter, I bring to light the complexities and challenges of identifying and describing grace as a datum of human experience. I also attempt to offer the Lonergan scholar some guidance by developing a set of normative criteria that will assist him in navigating these complexities and surmounting these challenges. The chapter is not an exercise in foundational theology but is written from a dialectical and methodological viewpoint. The dialectical and methodological work of the second chapter will prepare for the task of the third chapter. Chapter three compares Rahner’s and Lonergan’s theologies of grace; it focuses on a comparison of Lonergan’s notion of ‘being-in-love unrestrictedly’ and Rahner’s notion of the ‘supernatural existential’ in order to clarify their respective positions and to demonstrate an affinity in their writings on grace. Chapter four uses Rahner’s and Lonergan’s account of grace in terms of experience, developed in chapter three, to work out a theology of religion that responds to the challenges posed by post-modernism. My thesis in chapter four is that Rahner’s and Lonergan’s theologies of grace can ground the notion of a common consciousness of grace and take seriously the claim of a genuine variety of religious experiences.Thesis (PhD) — Boston College, 2009.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Theology

Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Conventional clotting factor concentrates have, until recently, been of intermediate purity, containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients

Long-Term Fluoride Release from Dental Resins Affects STRO-1+ Cell Behavior.

Fluoride-releasing restorative dental materials can be beneficial to remineralize dentin and help prevent secondary caries. However, the effects of fluoride release from dental materials on the activity of dental pulp stem cells are not known. Here we investigate whether different fluoride release kinetics from dental resins supplemented with modified hydrotalcite (RK-F10) or fluoride-glass filler (RK-FG10) could influence the behavior of a human dental pulp stem cell subpopulation (STRO-1(+) cells) known for its ability to differentiate toward an odontoblast-like phenotype. The 2 resins, characterized by similar physicochemical properties and fluoride content, exhibited different long-term fluoride release kinetics. Our data demonstrate that long-term exposure of STRO-1(+) cells to a continuous release of a low amount of fluoride by RK-F10 increases their migratory response to transforming growth factor β1 (TGF-β1) and stromal cell-derived factor 1 (SDF-1), both important promoters of pulp stem cell recruitment. Moreover, the expression patterns of dentin sialoprotein (dspp), dentin matrix protein 1 (dmp1), osteocalcin (ocn), and matrix extracellular phosphoglycoprotein (mepe) indicate a complete odontoblast-like cell differentiation only when STRO-1(+) cells were cultured on RK-F10. On the contrary, RK-FG10, characterized by an initial fluoride release burst and reduced lifetime of the delivery, did not elicit any significant effect on both STRO-1(+) cell migration and differentiation. Taken together, our results highlight the importance of taking into account fluoride release kinetics in addition to fluoride concentration when designing new fluoride-restorative materials

Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs)

Background: No previous prospective trials have been reported with capecitabine and gemcitabine (CAP-GEM) in patients with metastatic thymic epithelial tumors (TETs). We conducted a multicenter study to determine the activity and tolerability of this regimen in pretreated TETs. Patients and methods: A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival. Results: Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1-2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4-17). The 1- and 2-year survival rates were 80% and 67%, respectively. Conclusion: We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results

Evaluation of flu vaccination coverage among healthcare workers during a 3 years’ study period and attitude towards influenza and potential covid-19 vaccination in the context of the pandemic

(1) Background: vaccination of healthcare workers (HCWs) against seasonal influenza is considered the most effective way to protect HCWs, ensure patient’s safety and to maintain essential health care services during influenza epidemics. With the present study we aimed to evaluate the efficacy of incremental bundles of measures implemented during the last three flu campaigns and to assess the attitudes towards influenza vaccination and a potential vaccine against COVID-19 among HCWs, in a large university hospital in Pisa, Italy. (2) Methods: We described measures implemented during 2018/2019, 2019/2020 and 2020/2021 and assessed their impact on flu vaccine coverage (VC) among employees and residents in Pisa university hospital. We considered sex, profession and ward to investigate differences in uptake. In addition, in 2020 a survey was developed and distributed to all employees to evaluate flu and COVID-19 vaccines attitudes. (3) Results: during the 2018/19 and 2019/20 flu campaigns the overall VC rate among HCWs was, respectively, 10.2% and 11.9%. In 2020/21 the overall VC rate jumped to 39.3% (+230.6%). Results from the survey indicated a more positive attitude towards flu vaccine as compared to COVID-19 vaccines among the 10.6% of the staff members who responded to the survey. In addition, 70.97% of HCWs totally agreed that being vaccinated against influenza would be more important than the previous years because of COVID-19 emergency. (4) Conclusions: a significant increase in VC was observed in 2020/21, especially among those sub-groups with consistently lower uptake in previous years. The COVID-19 pandemic positively influenced flu vaccination uptake during the 2020/21 season

Analytical methods for describing charged particle dynamics in general focusing lattices using generalized Courant-Snyder theory

The dynamics of charged particles in general linear focusing lattices with quadrupole, skew-quadrupole, dipole, and solenoidal components, as well as torsion of the fiducial orbit and variation of beam energy is parametrized using a generalized Courant-Snyder (CS) theory, which extends the original CS theory for one degree of freedom to higher dimensions. The envelope function is generalized into an envelope matrix, and the phase advance is generalized into a 4D symplectic rotation, or a U(2) element. The 1D envelope equation, also known as the Ermakov-Milne-Pinney equation in quantum mechanics, is generalized to an envelope matrix equation in higher dimensions. Other components of the original CS theory, such as the transfer matrix, Twiss functions, and CS invariant (also known as the Lewis invariant) all have their counterparts, with remarkably similar expressions, in the generalized theory. The gauge group structure of the generalized theory is analyzed. By fixing the gauge freedom with a desired symmetry, the generalized CS parametrization assumes the form of the modified Iwasawa decomposition, whose importance in phase space optics and phase space quantum mechanics has been recently realized. This gauge fixing also symmetrizes the generalized envelope equation and expresses the theory using only the generalized Twiss function beta. The generalized phase advance completely determines the spectral and structural stability properties of a general focusing lattice. For structural stability, the generalized CS theory enables application of the Krein-Moser theory to greatly simplify the stability analysis. The generalized CS theory provides an effective tool to study coupled dynamics and to discover more optimized lattice designs in the larger parameter space of general focusing lattices.open3

The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel

Myotonia congenita (MC) is a skeletal-muscle hyperexcitability disorder caused by loss-of-function mutations in the ClC-1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30\ua0mutations located in the poorly characterized cytosolic C-terminal domain. In this study, we characterized, through patch clamp, seven ClC-1 mutations identified in patients affected by MC of various severities and located in the C-terminal region. The p.Val829Met, p.Thr832Ile, p.Val851Met, p.Gly859Val, and p.Leu861Pro mutations reside in the CBS2 domain, while p.Pro883Thr and p.Val947Glu are in the C-terminal peptide. We showed that the functional properties of mutant channels correlated with the clinical phenotypes of affected individuals. In addition, we defined clusters of ClC-1 mutations within CBS2 and C-terminal peptide subdomains that share the same functional defect: mutations between 829 and 835 residues and in residue 883 induced an alteration of voltage dependence, mutations between 851 and 859 residues, and in residue 947 induced a reduction of chloride currents, whereas mutations on 861 residue showed no obvious change in ClC-1 function. This study improves our understanding of the mechanisms underlying MC, sheds light on the role of the C-terminal region in ClC-1 function, and provides information to develop new antimyotonic drugs

Somatic Pairing of Chromosome 19 in Renal Oncocytoma Is Associated with Deregulated ELGN2-Mediated Oxygen-Sensing Response

Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney. Somatic pairing was associated with significant disruption of gene expression within the paired regions and resulted in the deregulation of the prolyl-hydroxylase ELGN2, a key protein that regulates the oxygen-dependent degradation of hypoxia-inducible factor (HIF). Overexpression of ELGN2 in renal oncocytoma increased ubiquitin-mediated destruction of HIF and concomitantly suppressed the expression of several HIF-target genes, including the pro-death BNIP3L gene. The transcriptional changes that are associated with somatic pairing of chromosome 19 mimic the transcriptional changes that occur following DNA amplification. Therefore, in addition to numerical and structural chromosomal abnormalities, alterations in chromosomal spatial dynamics should be considered as genomic events that are associated with tumorigenesis. The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma