The Doctrine of Baptism as an Ecumenical Factor

This ecumenical problem of apparent unity in disunity is the starting point for this study. All aspects of the problem, however, cannot be fully investigated here, so it has been narrowed down to show how a major ecumenical organization, The World Council of Churches, through its Assemblies and Commissions has become increasingly interested in the doctrine of Holy Baptism, to investigate why it has done so, and to trace the attempts it has made to formulate a doctrine of Baptism that it is hoped will resolve the problem of unity in disunity to the satisfaction of all concerned

Natural Theology in Lutheran Theology

While it is not our purpose within the limited compass of this paper to gather together the various philosophical and theological opinions of the past and the present held by those who doubt or reject the va1idity of the doctrine in question, it will be necessary briefly to refer to some of the most important of these opinions inasmuch as they have some bearing on shaping the attitude of some Lutheran theologians of more recent times in regard to the matter of Natural Theology and Natural Law

Traces of the female self : exploring the documentation of women’s art through traces, impressions, residues and self-portraiture via contemporary art practice

Women have always been present as artists, but not necessarily included within the canon of Western art history. Studying the canon is an accepted way of understanding the context of what has gone before, and in turn positioning ourselves within contemporary art practices and theories. However there is a disconnect when most of the individuals within the canon are nothing like us. Self-portraiture can be an embodied methodology, a starting point for an investigation that goes beyond oneself. Addressing the personal through my art practice also addresses a wider community of female artists. Through a studio-based investigation I have asked: What can visual art’s inherent capacity for generating and capturing traces, residues and impressions express in a material and conceptual way to explore self-identity and contribute to the current discourse about women artists’ history? How can these themes be visually expressed in new ways through contemporary selfportraiture, addressing absence and perspective in the documentation of women’s art? I explore these questions through experimental methods of making self-portraits. This research project considers the personal, examining representation of the self as an ontological enquiry into the roles of making and being. As a practice-led study, I pursue this line of enquiry as a means for exploring current structures of power, through a new body of work aimed at further informing Australian women’s art practice and its history.Masters by Researc

Hirnmetabolische Veränderungen bei chronischem Rückenschmerz

Chronische Rückenschmerzen gehören in Deutschland zu den häufigsten und kostenintensivsten Schmerzerkrankungen. Die Patienten weisen oft lange Krankengeschichten, eine dauerhaft eingeschränkte Lebensqualität und enorme psychische Belastungen auf. Auf Basis des biopsychosozialen Modells der Schmerzchronifizierung wird davon ausgegangen, dass neben klinischen und objektivierbaren Befunden, psychische Merkmale eine zentrale Rolle für die Entstehung, Aufrechterhaltung und Prognose von Schmerzsyndromen spielen. Außerdem besteht ein Zusammenhang zwischen dem Chronifizierungsstadium und dem Behandlungserfolg bei chronischen Schmerzpatienten. Mittels funktioneller Bildgebung wurde festgestellt, dass chronische Schmerzen und die damit verbundenen psychologischen und funktionellen Beeinträchtigungen auch im Zusammenhang mit Änderungen des Neurotransmitterstoffwechsels in schmerzverarbeitenden Hirnregionen (z.B. anteriorer cingulärer Kortex (aCC), insulärer Kortex) stehen. Die Konzentrationen der im menschlichen Gehirn wichtigsten Neurotransmitter GABA (γ-Aminobuttersäure) und Glutamat sind sowohl bei chronischen Schmerzen als auch bei psychischen Erkrankungen wie Depression und Angsterkrankungen verändert. In dieser Studie wurde die Magnetresonanzspektroskopie (1H-MRS) genutzt, um Neurotransmitter im Gehirn in vivo zu quantifizieren und ein schmerzbegleitendes Ungleichgewicht zwischen erregend (glutamatergen) und hemmend (gabaergen) wirkenden Neurotransmittern bei Patienten mit chronischen unspezifischen Rückenschmerzen nachzuweisen sowie den Zusammenhang zu psychologischen und klinischen Befunden zu untersuchen. Hierzu wurden bei 19 Patienten mit chronischen, unspezifischen Schmerzen (>3 Monate) im Rückenbereich sowie bei 19 nach Alter und Geschlecht parallelisierten gesunden Kontrollpersonen psychologische (Angst, Depressivität) und Schmerzmerkmale (Chronifizierungsstadium, Schmerzintensität, Schmerzdauer) mittels Fragebögen erfasst. Akute psychiatrische Erkrankungen wurden in einem standardisierten, klinischen Interview (SKID) ausgeschlossen. Die Neurotransmitter Glutamat und GABA sowie Glutamat/GABA Verhältnisse im aCC und im insulären Kortex wurden mittels 1H-MRS quantifiziert. Es zeigte sich eine hohe Varianz der Glutamat/GABA Verhältnisse von Patienten und Kontrollpersonen in beiden gemessenen Hirnregionen. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden. Das Merkmal „Angst“ war eine signifikante Einflussvariable auf die Konzentration von Glutamat in Insula und aCC. Das Außerdem zeigte sich innerhalb der Patientengruppe ein signifikanter Einfluss der Schmerzintensität auf GABA und Glutamat in der Insula. Des Weiteren wurde mit zunehmendem Chronifizierungsstadium eine Abnahme des Neurotransmitters Glutamat im aCC nachgewiesen. Dieser Zusammenhang wurde in der vorliegenden Studie erstmals beschrieben. In Übereinstimmung mit dem aktuellen Forschungsstand lässt sich ableiten, dass dem aCC und der Insula im Prozess der Schmerzchronifizierung unterschiedliche Rollen zukommen: Veränderungen der Botenstoffe standen im aCC in Zusammenhang mit psychischen Merkmalen, in der Insula mit der Schmerzintensität. Die dargestellten Ergebnisse müssen unter Berücksichtigung folgender methodischer Limitationen interpretiert werden: mit 1H-MRS gemessene Neurotransmitterkonzentrationen repräsentieren Summenwerte der Messvolumina in den Hirnregionen, sodass kein Rückschluss auf die Herkunft der Metaboliten (Glutamat ist sowohl Metabolit im Energiestoffwechsel als auch Neurotransmitter) gezogen werden kann. Durch die Durchführung eines querschnittlichen Studiendesigns kann die Kausalität der gemessenen Zusammenhänge nicht bewertet werden. In Folgestudien sollten die nachgewiesen Effekte an größeren Stichproben und Kontrollgruppen überprüft werden. In dieser Studie konnte nachgewiesen werden, dass sowohl klinische als auch psychische Merkmale von Patienten mit chronischen Rückenschmerzen im Zusammenhang mit Änderungen von Neurotransmittern in den schmerzverarbeitenden Hirnregionen aCC und Insula stehen. Die Vorgänge der zentralnervösen Schmerzverarbeitung und Chronifizierung sowie insbesondere den Bezug zu psychosozialen Merkmalen zu verstehen, stellt eine große Herausforderung für die aktuelle Schmerzforschung dar. In unserer Studie ist es gelungen eine Reihe von Einflussfaktoren zu identifizieren und die Bedeutung einer ausführlichen, individuellen Befunderhebung von sowohl psychischen als auch klinischen Parametern zu belegen

Improved Endpoints for Cancer Immunotherapy Trials

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation

Fragebogenentwicklung zur Lebensgestaltung

"Die soziologische Forschung zum Wohlbefinden fragt nach der Bedeutung einzelner Bereiche des Lebens für die Zufriedenheit der Menschen. Dabei ist zum einen eine allgemeine Einschätzung der Zufriedenheit dieser Bereiche interessant, zum anderen auch die Gewichtung der Bereiche für diese Zufriedenheit. Diese Herangehensweise kann sich die Sozialpsychologie zunutze machen, indem sie solche Fragestellungen auf der Ebene des Individuums stellt. Der Fragebogen zur Lebensgestaltung zeigt eine Möglichkeit auf, wie die beiden Untersuchungsebenen der allgemeinen soziologischen Wichtigkeits-Einschätzung und der individuellen Gewichtung mithilfe eines einzigen Fragebogens sinnvoll erfasst werden können."[Autorenreferat]"Questionnaire Development: A Lifestyle Orientation Scale Sociological research on well-being discusses the impact that the spheres of life have on people’s contentment. This concerns both an overall estimation of their well-being and the importance of these spheres for such a well-being. Social psychology may adopt this approach and apply it to the individual level. The Lifestyle Orientation Scale presents a way to cover the two fields of interest, the general sociological importance-ratings and the individual social psychological differentiation of these ratings, in one questionnaire."[author´s abastract

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI)

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels

Improvement of IFNg ELISPOT Performance Following Overnight Resting of Frozen PBMC Samples Confirmed Through Rigorous Statistical Analysis

Immune monitoring of functional responses is a fundamental parameter to establish correlates of protection in clinical trials evaluating vaccines and therapies to boost antigen-specific responses. The IFNg ELISPOT assay is a well-standardized and validated method for the determination of functional IFNg-producing T-cells in peripheral blood mononuclear cells (PBMC); however, its performance greatly depends on the quality and integrity of the cryopreserved PBMC. Here, we investigate the effect of overnight (ON) resting of the PBMC on the detection of CD8-restricted peptide-specific responses by IFNg ELISPOT. The study used PBMC from healthy donors to evaluate the CD8 T-cell response to five pooled or individual HLA-A2 viral peptides. The results were analyzed using a modification of the existing distribution free resampling (DFR) recommended for the analysis of ELISPOT data to ensure the most rigorous possible standard of significance. The results of the study demonstrate that ON resting of PBMC samples prior to IFNg ELISPOT increases both the magnitude and the statistical significance of the responses. In addition, a comparison of the results with a 13-day preculture of PBMC with the peptides before testing demonstrates that ON resting is sufficient for the efficient evaluation of immune functioning

Validation of a HLA-A2 tetramer flow cytometric method, IFNgamma real time RT-PCR, and IFNgamma ELISPOT for detection of immunologic response to gp100 and MelanA/MART-1 in melanoma patients

<p>Abstract</p> <p>Background</p> <p>HLA-A2 tetramer flow cytometry, IFNγ real time RT-PCR and IFNγ ELISPOT assays are commonly used as surrogate immunological endpoints for cancer immunotherapy. While these are often used as research assays to assess patient's immunologic response, assay validation is necessary to ensure reliable and reproducible results and enable more accurate data interpretation. Here we describe a rigorous validation approach for each of these assays prior to their use for clinical sample analysis.</p> <p>Methods</p> <p>Standard operating procedures for each assay were established. HLA-A2 (A*0201) tetramer assay specific for gp100_209(210M)and MART-1_26–35(27L), IFNγ real time RT-PCR and ELISPOT methods were validated using tumor infiltrating lymphocyte cell lines (TIL) isolated from HLA-A2 melanoma patients. TIL cells, specific for gp100 (TIL 1520) or MART-1 (TIL 1143 and TIL1235), were used alone or spiked into cryopreserved HLA-A2 PBMC from healthy subjects. TIL/PBMC were stimulated with peptides (gp100₂₀₉, gp100_pool, MART-1_27–35, or influenza-M1 and negative control peptide HIV) to further assess assay performance characteristics for real time RT-PCR and ELISPOT methods. Validation parameters included specificity, accuracy, precision, linearity of dilution, limit of detection (LOD) and limit of quantification (LOQ). In addition, distribution was established in normal HLA-A2 PBMC samples. Reference ranges for assay controls were established.</p> <p>Results</p> <p>The validation process demonstrated that the HLA-A2 tetramer, IFNγ real time RT-PCR, and IFNγ ELISPOT were highly specific for each antigen, with minimal cross-reactivity between gp100 and MelanA/MART-1. The assays were sensitive; detection could be achieved at as few as 1/4545–1/6667 cells by tetramer analysis, 1/50,000 cells by real time RT-PCR, and 1/10,000–1/20,000 by ELISPOT. The assays met criteria for precision with %CV < 20% (except ELISPOT using high PBMC numbers with %CV < 25%) although flow cytometric assays and cell based functional assays are known to have high assay variability. Most importantly, assays were demonstrated to be effective for their intended use. A positive IFNγ response (by RT-PCR and ELISPOT) to gp100 was demonstrated in PBMC from 3 melanoma patients. Another patient showed a positive MART-1 response measured by all 3 validated methods.</p> <p>Conclusion</p> <p>Our results demonstrated the tetramer flow cytometry assay, IFNγ real-time RT-PCR, and INFγ ELISPOT met validation criteria. Validation approaches provide a guide for others in the field to validate these and other similar assays for assessment of patient T cell response. These methods can be applied not only to cancer vaccines but to other therapeutic proteins as part of immunogenicity and safety analyses.</p