Adjoint harmonic balance method for forced response analysis in turbomachinery

This paper describes the derivation and implementation of the discrete adjoint equations based on frequency domain methods (linear harmonics and harmonic balance) within a turbomachinery CFD code. Applications to model problems are presented which demonstrate the potential of the method for multidisciplinary turbomachinery problems, e.g. aeroelastics or aeroacoustics

Klinische Beurteilung der Wirksamkeit und Toxizität der Lu-177-PSMA-Ligandentherapie bei kastrationsresistentem Prostatakarzinom

Das Prostatakarzinom ist weltweit eine der häufigsten malignen Neoplasien des Mannes und gewinnt in unserer Gesellschaft im demographischen Wandel zunehmend an Bedeutung. Insbesondere die Behandlung der Männer mit einem kastrationsresistenten, metastasierten Prostatakarzinom stellt eine besondere Herausforderung dar und bringt, als Tumorerkrankung im Endstadium, spezifische Ansprüche an seine Therapie mit sich. Die Lu-177-PSMALigandentherapie ist eine Radionuklidtherapie, die aktuell als individueller Heilversuch zur Therapie des kastrationsresistenten, metastasierten Prostatakarzinoms eingesetzt wird und durch eine Bindung an das prostataspezifische Membranantigen (PSMA) der Tumorzellen eine endogene Bestrahlung des Tumors bewirkt. Ziel dieser Dissertation war eine retrospektive Analyse der Wirksamkeit und Toxizität der Lu-177-PSMA-Ligandentherapie in einem Patientenkollektiv von 56 Patienten, die im Zeitraum vom 01.11.2014 bis zum 31.12.2018 an der Uniklinik Köln behandelt wurden. Alle untersuchten Patienten hatten ein kastrationsresistentes, metastasiertes Prostatakarzinom und waren multipel vortherapiert. Die Datenerhebung erfolgte aus den elektronischen und analogen Patientenakten. Die primären Studienendpunkte dieser Analyse waren die Auswirkungen der Lu-177-PSMALigandentherapie auf das Gesamtüberleben der Patienten und das Therapieansprechen im PSMA-PET/CT klassifiziert nach RECIST und PERCIST Kriterien. Primärer Surrogatendpunkt war das Therapieansprechen, gemessen am PSA-Abfall und klassifiziert nach PCWGKriterien. Als sekundäre Studienendpunkte wurden die Sicherheit und Verträglichkeit der Therapie anhand einer Klassifikation nach CTCAE gewählt. Die 56 Patienten des Kollektivs erhielten mindestens einen und maximal vier Therapiezyklen. Insgesamt wurden 139 Therapiezyklen mit einer mittleren Therapieaktivität von 6,8 GBq pro Zyklus durchgeführt. 26 Patienten (54%) hatten einen PSA-Abfall ≥ 50% unter Therapie und damit eine „Response“, 13 (27%) hatten eine „Stable Disease“ und 9 (19%) eine „Progression“ nach PCWG1-Kriterien. 39 Patienten (70%) hatten einen PSA-Abfall in beliebiger Höhe. 10 Patienten, die nach dem ersten Therapiezyklus „Non-Responder“ nach PCWG1- Kriterien waren, wechselten nach dem zweiten Therapiezyklus in die „Response“. In der Bildauswertung der Lymphknoten- und Organmetastasen im PSMA-PET/CT hatten 10 Patienten (37%) eine „Partial Response“ nach RECIST und 15 (54%) eine „Partial Metabolic Response“ nach PERCIST. Die verbreitetste Therapietoxizität war eine Anämie. Sie trat bei 17 Patienten (32%) auf, wovon 15 (28%) eine Verschlechterung um einen Grad nach CTCAE und zwei (4%) eine Verschlechterung um zwei Grad nach CTCAE hatten. Eine schwere Hämatotoxizität (Grad 3) trat insgesamt bei vier Patienten (8%) auf. Kein Patient erlitt eine schwere Hepatotoxizität oder Nephrotoxizität und es gab keine therapieassoziierten Todesfälle. Das mediane Überleben im Kollektiv lag bei 16 Monaten. 26 Patienten sind im Beobachtungszeitraum verstorben. Patienten mit einem PSA-Abfall unter Lu-177-PSMA-Ligandentherapie hatten ein signifikant längeres medianes Überleben (p<0,05) als Patienten ohne PSA-Abfall (22 vs. 7 Monate). Drüber hinaus zeigten die Parameter PSA-Abfall ≥ 50% (p=0,001), > 2 erhaltene Therapiezyklen (p=0,001), eine kumulative Gesamttherapieaktivität > 15GBq (p=0,001) und eine AP ≤ 220 [U/l] vor Therapiebeginn (p=0,001) einen statistisch signifikanten Zusammenhang mit einem längeren medianen Überleben, der auch in der multivariaten Cox- Regression bestehen blieb. Die vorliegende retrospektive Arbeit zeigt somit ein gutes Therapieansprechen und eine geringe Therapietoxizität der Lu-177-PSMA-Ligandentherapie bei Patienten mit einem kastrationsresistenten, metastasierten Prostatakarzinom. Die Daten weisen darauf hin, dass mindestens zwei Therapiezyklen durchgeführt und die maximal verträgliche Dosis appliziert werden sollte, um einen Therapieeffekt zu erzielen. Vor allem die gute Therapieverträglichkeit und die unkomplizierte Anwendung sind Qualitäten von großer Bedeutung bei einer palliativen Therapiemaßnahme wie dieser und verschafft der Lu-177-PSMA-Ligandentherapie einen nennenswerten Vorteil gegenüber anderen Drittlinientherapien. Diese Dissertation bestätigt also die bisherigen Ergebnisse der Literatur und unterstützt die Auffassung, dass es ein modernes Therapieverfahren mit großem Zukunftspotential ist

An Efficient Implementation of Second Quantization-Based Many-Body Methods for Electrons and its Application to Coupled-Cluster with Arbitrary Excitation Level

This thesis deals with selected aspects of a new implementation of many-body methods which can be formulated in the framework of second quantization, in particular the coupled-cluster (CC) method with arbitrary excitation level. Coupled-cluster is one of the most successful and widely used quantum chemical methods for accurate calculations on small to medium-sized molecules. Since it employs a nonlinear parametrization of the wave function, its implementation is rather difficult, in particular if higher (i.e. more than double) excitations are to be included. The latter is necessary to obtain highly accurate results and also as a prerequisite for the generalization to multi-reference cases. The implementation described here has a twofold focus. One is on generality and flexibility regarding the method to be implemented, the other is on efficiency. To achieve flexibility, it is useful to have a machinery which automatically derives working equations for a given method. We realize this by applying techniques of second quantization. This work treats in particular the last step of this procedure, namely the simplification of the resulting equations by the identification of equivalent terms. The algorithm used here is based on the interpretation of algebraic terms as graphs. The derived CC equations then have to be solved iteratively. The efficiency of the program is mainly determined by the evaluation of the occurring expressions, which has to be done in each iteration step. The evaluation is split up in a sequence of tensor contractions. Their generic implementation is complicated by the particular structure of the involved tensors. We reduce each contraction to a sequence of matrix multiplications, which requires a previous data rearranging. But since matrix multiplication is the most efficient operation on modern computers, this additional effort pays off. Preliminary tests show that our program is at least as fast as the most efficient general coupled-cluster implementation so far, and the relation is expected to improve for calculations with larger basis sets where the matrix multiplication becomes the time-determining step. Finally, we give an outlook to possible further developments. In particular, the preparation of the equations before the actual evaluation (factorization) offers much potential for optimizations which we do not exploit at the moment, in contrast to the program with which we compare, which employs at least a partial optimization at this point

A Randomized Controlled Trial Comparing two Cognitive-Behavioral Programs for Adolescent Girls with Subclinical Depression: A School-Based Program (Op Volle Kracht) and a Computerized Program (SPARX)

Limited research has indicated the effectiveness of the school-based Cognitive Behavioral Therapy (CBT) prevention program ‘Op Volle Kracht (OVK)’ and the computerized CBT program ‘SPARX’ in decreasing depressive symptoms. Therefore, a randomized controlled trial of the effectiveness of OVK and SPARX was conducted among Dutch female adolescents (n = 208, mean age = 13.35) with elevated depressive symptoms. Participants were randomly assigned to one of four conditions: OVK only (n = 50), SPARX only (n = 51), OVK and SPARX combined (n = 56) and a monitoring control condition (n = 51). Participants in the first three conditions received OVK lessons and/or the SPARX game. Depressive symptoms were assessed before interventions started, weekly during the interventions, and immediately after the interventions ended, with follow-up assessments at 3, 6 and 12 months. Intention to treat results showed that depressive symptoms decreased in all conditions (F(12, 1853.03) = 14.62, p < .001), with no difference in depressive symptoms between conditions. Thus, all conditions, including the monitoring control condition, were equally effective in reducing depressive symptoms. Possible explanations for the decrease of depressive symptoms in all conditions are discussed and suggestions for future research are provided. Dutch Trial Register: NTR3737

Polarized Proton Beams from Laser-induced Plasmas

We report on the concept of an innovative source to produce polarized proton/deuteron beams of a kinetic energy up to several GeV from a laser-driven plasma accelerator. Spin effects have been implemented into the PIC simulation code VLPL to make theoretical predictions about the behavior of proton spins in laser-induced plasmas. Simulations of spin-polarized targets show that the polarization is conserved during the acceleration process. For the experimental realization, a polarized HCl gas-jet target is under construction using the fundamental wavelength of a Nd:YAG laser system to align the HCl bonds and simultaneously circular polarized light of the fifth harmonic to photo-dissociate, yielding nuclear polarized H atoms. Subsequently, their degree of polarization is measured with a Lamb-shift polarimeter. The final experiments, aiming at the first observation of a polarized particle beam from laser-generated plasmas, will be carried out at the 10 PW laser system SULF at SIOM/Shanghai.Comment: 7 pages, 7 figure

Filling the Gap:A Feasibility Study of a COPD-Specific Breathlessness Service

Refractory breathlessness is a devastating symptom in chronic obstructive pulmonary disease (COPD). Symptom-focused breathlessness services, involving palliative care teams, offer individualized support but are not yet widely available for people with nonmalignant disease among which COPD. Our primary aim was to demonstrate the feasibility of setting up a breathlessness service specifically for COPD patients within a respiratory outpatient clinic. Our secondary aims were to assess how many sessions patients need to complete the intervention; to obtain an indication of effect size (on the Chronic Respiratory Questionnaire (CRQ), subset mastery domain); and to evaluate patient and professional satisfaction. We conducted a non-randomized single-center feasibility study. Participants had COPD and refractory breathlessness. During at least one session with a respiratory nurse and a pulmonologist, and one session with a physiotherapist, patients learned non-pharmacological interventions to manage breathlessness. Of 34 screened patients, 19 were included. All completed the intervention. A median of two clinical visits and two telephone calls were needed to complete the intervention. The mean improvement of 1.55 in CRQ, mastery domain, significantly exceeded the clinically important difference of 0.5. The service was rated as excellent by the eight patients who completed the survey. The health professional team gave positive feedback on the experience of delivering the intervention. Delivery of a breathlessness service for COPD outpatients with refractory breathlessness appears feasible, easy to implement in a respiratory outpatient clinic, and has the potential to be effective. A randomized controlled clinical trial is needed to test effectiveness and cost-effectiveness in this context

Chironomid-based temperature reconstruction for the Eemian Interglacial (MIS 5e) at Sokli, northeast Finland

Peer reviewe

Changes in Alcohol-Related Brain Networks Across the First Year of College: A Prospective Pilot Study Using fMRI Effective Connectivity Mapping

The upsurge in alcohol use that often occurs during the first year of college has been convincingly linked to a number of negative psychosocial consequences and may negatively affect brain development. In this longitudinal functional magnetic resonance imaging (fMRI) pilot study, we examined changes in neural responses to alcohol cues across the first year of college in a normative sample of late adolescents. Participants (N=11) were scanned three times across their first year of college (summer, first semester, second semester), while completing a go/no-go task in which images of alcoholic and non-alcoholic beverages were the response cues. A state-of-the-art effective connectivity mapping technique was used to capture spatiotemporal relations among brain regions of interest (ROIs) at the level of the group and the individual. Effective connections among ROIs implicated in cognitive control were greatest at the second assessment (when negative consequences of alcohol use increased), and effective connections among ROIs implicated in emotion processing were lower (and response times were slower) when participants were instructed to respond to alcohol cues compared to non-alcohol cues. These preliminary findings demonstrate the value of a prospective effective connectivity approach for understanding adolescent changes in alcohol-related neural processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/123049/1/Changes in Alcohol-Related Brain Networks Across the First Year of College_A Prospective Pilot Study Using fMRI Effective Connectivity Mapping.pd

Simulation of Polarized Beams from Laser-Plasma Accelerators

The generation of polarized particle beams still relies on conventional particle accelerators, which are typically very large in scale and budget. Concepts based on laser-driven wake-field acceleration have strongly been promoted during the last decades. Despite many advances in the understanding of fundamental physical phenomena, one largely unexplored issue is how the particle spins are influenced by the huge magnetic fields of plasma and, thus, how highly polarized beams can be produced. The realization of laser-plasma based accelerators for polarized beams is now being pursued as a joint effort of groups from Forschungszentrum J\"ulich (Germany), University of Crete (Greece), and SIOM Shanghai (China) within the ATHENA consortium. As a first step, we have theoretically investigated and identified the mechanisms that influence the beam polarization in laser-plasma accelerators. We then carried out a set of Particle-in-cell simulations on the acceleration of electrons and proton beams from gaseous and foil targets. We could show that intense polarized beams may be produced if pre-polarized gas targets of high density are employed. In these proceedings we further present that the polarization of protons in HT and HCl gas targets is largely conserved during laser wake-field acceleration, even if the proton energies enter the multi-GeV regime. Such polarized sources for electrons, protons, deuterons and $^{3}$He ions are now being built in J\"ulich. Proof-of-principle measurements at the (multi-)PW laser facilities PHELIX (GSI Darmstadt) and SULF (Shanghai) are in preparation.Comment: submitted to IO

Effectiveness of the home-based alcohol prevention program "In control: No alcohol!": study protocol of a randomized controlled trial

Contains fulltext : 99285.pdf (postprint version ) (Open Access)Background: In the Netherlands, children start to drink at an early age; of the Dutch 12-year olds, 40% reports lifetime alcohol use, while 9.7% reports last-month drinking. Starting to drink at an early age puts youth at risk of developing several alcohol-related problems later in life. Recently, a home-based prevention program called "In control: No alcohol!" was developed to delay the age of alcohol onset in children. The main aim of this project is to conduct a Randomized Controlled Trial (RCT) to evaluate the effectiveness of the program. Methods/Design: The prevention program will be tested with an RCT among mothers and their 6 grade primary school children (11-12 years old), randomly assigned to the prevention or control condition. The program consists of five printed magazines and an activity book designed to improve parental alcohol-specific socialization. Parent-child dyads in the control group receive a factsheet information brochure, which is the standard alcohol brochure of the Trimbos Institute (the Netherlands Institute for Mental Health and Addiction). Outcome measures are initiation of alcohol use (have been drinking at least one glass of alcohol), alcohol-specific parenting, susceptibility to drinking alcohol, alcohol expectancies, self-efficacy, and frequency and intensity of child alcohol use. Questionnaires will be administered online on secured Internet webpages, with personal login codes for both mothers and children. Mothers and children in both the experimental and control condition will be surveyed at baseline and after 6, 12, and 18 months (follow-ups). Discussion: The present study protocol presents the design of an RCT evaluating the effectiveness of the home-based "In control: No alcohol!" program for 6 grade primary school children (11-12 years old). It is hypothesized that children in the prevention condition will be less likely to have their first glass of alcohol, compared to the control condition. When the prevention appears to be effective, it can easily and relatively quickly be implemented as a standard alcohol prevention program on a large scale.8 p