Improved actions, the perfect action, and scaling by perturbation theory in Wilsons renormalization group: the two dimensional O(N)O(N)-invariant non linear σ\sigma-model in the hierarchical approximation

We propose a method using perturbation theory in the running coupling constant and the idea of scaling to determine improved actions for lattice field theories combining Wilson's renormalization group with Symanzik's improvement program . The method is based on the analysis of a single renormalization group transformation. We test it on the hierarchical $O(N)$ invariant $\sigma$ model in two dimensions.Comment: 13 pages in LaTeX, 5 uuencoded PS figures included with epsfig.sty (including of ps-files fixed

Analyse der Effekte der MEK1S212N-Mutation hinsichtlich Signaltransduktion und Phänotyp in Rattenfibroblasten und HEK293-Zellen

Der MAPK-Signalweg ist einer der zentralen Forschungsschwerpunkte in der aktuellen Krebsforschung. Etwa 30 % der Krebserkrankungen (Nandan und Yang 2011; Hoshino et al. 1999) lassen sich auf Mutationen in diesem Signalweg zurückführen. Darunter befindet sich auch die Gruppe der kolorektalen Karzinome, die die dritthäufigste Ursache für vorzeitige Todesfälle durch Tumoren in Deutschland ausmachen (Robert Koch-Institut 2019). MEK-Proteine nehmen eine zentrale Stellung innerhalb des MAPK-Signalwegs zwischen Raf und ERK ein. Mutationen in MEK1 können so z. B. die Proliferation einer Zelle stark beeinflussen (Jindal et al. 2017). In der Kolonkarzinomzelllinie LIM1215 ist bei einer Panel-DNA-Sequenzierung die MEK1S212N-Mutation gefunden worden. Diese Zelllinie ist aus dem HNPCC eines Patienten mit Lynch-Syndrom generiert worden. Ziel dieser Arbeit ist es, festzustellen, ob die Mutation eine funktionelle Rolle im Darmkrebs spielt. Dafür soll geklärt werden, ob eine Expression von MEK1(S212N) in vitro in den eigens dafür eingesetzten Zellsystemen zu einer Steigerung von phosphoryliertem ERK1/2 führt und damit eine konstitutiv aktive Form des MEK1 darstellt. Weiterhin sollen im murinen 208F-Zellsystem eventuelle Änderungen der Zellmorphologie in Abhängigkeit der Expression von MEK1(S212N) detektiert werden. Es sind verschiedene MEK1-Konstrukte generiert und in Trägerplasmide kloniert worden, um mittels lentiviraler Partikel die Zelllinien Hek293 und 208F stabil zu transduzieren. Anschließend sind mittels Western Blot und Mikroskopie die Auswirkungen von MEK1S212N auf die biochemischen und morphologischen Eigenschaften der Zellen analysiert worden. Die in der vorliegenden Arbeit vorgestellten Daten belegen, dass die MEK1S212N-Mutation in einzelnen Karzinomen nachgewiesen werden kann. Es ist außerdem gelungen, mit den genannten Methoden stabile transgene Zellen herzustellen, die das MEK1-Konstrukt ausreichend stark überexprimierten. Jedoch ist mit den gewählten Methoden keine Veränderung der Signalwegaktivität oder Veränderung der Zellmorphologie durch eine Expression dieser Mutation nachgewiesen worden. Die funktionelle Relevanz für die betroffenen Zellen und das Gewebe bleibt unklar.  The MAPK signaling pathway is a major focus of current cancer research. About 30 % of all cancers show activating mutations in the MAPK signaling pathway (Nandan and Yang 2011, Hoshino et al. 1999). A major example of tumors in which MAPK pathway mutations are important is colorectal cancer (CRC). CRC is the third most common cause of death by cancer in Germany (Robert Koch-Institute 2019). The MEK isoforms play a central role between ERK and Raf in the MAPK signaling pathway. Mutations in the MEK1 gene have been shown to alter the proliferation of cell (Jindal et al. 2017). By genome panel sequencing it was found that a colorectal cancer cell line harbours a MEK1S212N mutation. This cell line was derived from a hereditary non-polyposis colorectal cancer (HNPCC) of a patient who suffered from Lynch syndrome. The aim of the present thesis was to characterize the hitherto uncharacterized MEK1S212N mutation in order to assess if it may be implicated in the development of CRC. The central questions were if mutations of MEK1 are present in tumors, and if the expression of MEK1S212N in vitro leads to increased activation of the downstream protein, ERK1/2. To address this question, the MEK1 gene of a cohort of carcinomas was sequenced. Furthermore, different constructs of MEK1 mutants were generated and cloned into lentiviral plasmids. These transgenes were then introduced in Hek293 and 208F cells, and the effect of the synthesis of mutant MEK1 proteins was subsequently investigated using biochemical and morphological methods. The data presented in this thesis shows that MEK1S212N was detected in a few carcinomas. Furthermore, it was possible to generate stable transgene cell lines that significantly express the MEK constructs. However, with the methods used in this thesis, no change in the activity of the signaling pathway and no change of the cell morphology due to the expression of MEK1S212N could be detected. With these results, the functional relevance for affected cells and tissues remains unclear

Self-consistent Calculation of Real Space Renormalization Group Flows and Effective Potentials

We show how to compute real space renormalization group flows in lattice field theory by a self-consistent method. In each step, the integration over the fluctuation field (high frequency components of the field) is performed by a saddle point method. The saddle point depends on the block-spin. Higher powers of derivatives of the field are neglected in the actions, but no polynomial approximation in the field is made. The flow preserves a simple parameterization of the action. In this paper we treat scalar field theories as an example.Comment: 52 pages, uses pstricks macro, three ps-figure

Economic evaluation alongside a randomized controlled trial of blended cognitive-behavioral therapy for patients suffering from major depressive disorder

OBJECTIVE: This study aimed to investigate the cost-effectiveness of blended cognitive-behavioral therapy (CBT) compared to standard CBT for adult patients suffering from major depressive disorder (MDD). DESIGN: A cost-utility analysis alongside the randomized controlled ENTER trial. SETTING: Center for Telepsychiatry, Mental Health Services in the Region of Southern Denmark, Denmark. PARTICIPANTS: The study included 76 patients suffering from MDD. INTERVENTIONS: The patients in the intervention group received blended CBT treatment comprising a combination of online modules and face-to-face consultations with a psychologist. The patients in the control group received standard CBT treatment, that is, solely face-to-face consultations with a psychologist. The treatment period was 12 weeks. OUTCOME MEASURES: Cost-effectiveness was reported as incremental cost-effectiveness ratio. A micro-costing approach was applied to evaluate the savings derived. Changes in quality-adjusted life-years (QALYs) were estimated using the EuroQol 5-Dimensions 5-Levels questionnaire at the baseline and the six-month follow-up. RESULTS: Data for 74 patients were included in the primary analysis. The adjusted QALY difference between blended CBT and standard CBT was −0.0291 (95% CI: −0.0535 to −0.0047), and the adjusted difference in costs was -£226.32 (95% CI: −300.86 to −151.77). Blended CBT was estimated to have a 6.6% and 3.1% probability of being cost-effective based on thresholds of £20,000 and £30,000. CONCLUSION: Compared to standard CBT, blended CBT represents a cost-saving but also a loss in QALYs for patients suffering from MDD. However, results should be carefully interpreted, given the small sample size. Future research involving larger replication studies focusing on other aspects of blended CBT with more patient involvement is advised. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov: S-20150150

Basic newborn care and neonatal resuscitation: a multi-country analysis of health system bottlenecks and potential solutions.

BACKGROUND: An estimated two-thirds of the world's 2.7 million newborn deaths could be prevented with quality care at birth and during the postnatal period. Basic Newborn Care (BNC) is part of the solution and includes hygienic birth and newborn care practices including cord care, thermal care, and early and exclusive breastfeeding. Timely provision of resuscitation if needed is also critical to newborn survival. This paper describes health system barriers to BNC and neonatal resuscitation and proposes solutions to scale up evidence-based strategies. METHODS: The maternal and newborn bottleneck analysis tool was applied by 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops engaged technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" that hinder the scale up of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for BNC and neonatal resuscitation. RESULTS: Eleven of the 12 countries provided grading data. Overall, bottlenecks were graded more severely for resuscitation. The most severely graded bottlenecks for BNC were health workforce (8 of 11 countries), health financing (9 out of 11) and service delivery (7 out of 9); and for neonatal resuscitation, workforce (9 out of 10), essential commodities (9 out of 10) and service delivery (8 out of 10). Country teams from Africa graded bottlenecks overall more severely. Improving workforce performance, availability of essential commodities, and well-integrated health service delivery were the key solutions proposed. CONCLUSIONS: BNC was perceived to have the least health system challenges among the seven maternal and newborn intervention packages assessed. Although neonatal resuscitation bottlenecks were graded more severe than for BNC, similarities particularly in the workforce and service delivery building blocks highlight the inextricable link between the two interventions and the need to equip birth attendants with requisite skills and commodities to assess and care for every newborn. Solutions highlighted by country teams include ensuring more investment to improve workforce performance and distribution, especially numbers of skilled birth attendants, incentives for placement in challenging settings, and skills-based training particularly for neonatal resuscitation

Kangaroo mother care: a multi-country analysis of health system bottlenecks and potential solutions.

BACKGROUND: Preterm birth is now the leading cause of under-five child deaths worldwide with one million direct deaths plus approximately another million where preterm is a risk factor for neonatal deaths due to other causes. There is strong evidence that kangaroo mother care (KMC) reduces mortality among babies with birth weight <2000 g (mostly preterm). KMC involves continuous skin-to-skin contact, breastfeeding support, and promotion of early hospital discharge with follow-up. The World Health Organization has endorsed KMC for stabilised newborns in health facilities in both high-income and low-resource settings. The objectives of this paper are to: (1) use a 12-country analysis to explore health system bottlenecks affecting the scale-up of KMC; (2) propose solutions to the most significant bottlenecks; and (3) outline priority actions for scale-up. METHODS: The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale-up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for KMC. RESULTS: Marked differences were found in the perceived severity of health system bottlenecks between Asian and African countries, with the former reporting more significant or very major bottlenecks for KMC with respect to all the health system building blocks. Community ownership and health financing bottlenecks were significant or very major bottlenecks for KMC in both low and high mortality contexts, particularly in South Asia. Significant bottlenecks were also reported for leadership and governance and health workforce building blocks. CONCLUSIONS: There are at least a dozen countries worldwide with national KMC programmes, and we identify three pathways to scale: (1) champion-led; (2) project-initiated; and (3) health systems designed. The combination of all three pathways may lead to more rapid scale-up. KMC has the potential to save lives, and change the face of facility-based newborn care, whilst empowering women to care for their preterm newborns