Total Body Irradiation (TBI) in Pediatric Patients: A Single-center Experience after 30 Years of Low-dose Rate Irradiation

Abstract : Purpose: : To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. Patients and Methods: : 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. Results: : The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG ≥3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. Conclusion: : As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indication

Essential work of fracture of poly(ϵ-caprolactone)/boehmite alumina nanocomposites: Effect of surface coating

The essential work of fracture (EWF) approach has been adopted to reveal the effect of nanofillers on the toughness of poly(ε-caprolactone)/boehmite alumina (PCL/BA) nanocomposites. Synthetic BA particles of different surface treatments were dispersed in the PCL matrix by extrusion melt compounding. The morphology of composites was studied by scanning electron microscopy. Differential scanning calorimetry and wide angle X-ray scattering were used to detect changes in the crystalline structure of PCL. Besides the mode I type EWF tests, dynamic mechanical analysis (DMA) and quasi-static tensile tests were applied to study the effect of BA nanofillers on the mechanical properties. BA was homogenously dispersed and acted as heterogeneous crystallization nucleant and non-reinforcing filler in PCL. The tensile modulus and yield strength slightly increased, whereas the yield strain decreased with increasing BA content (up to 10 wt%). Effect of the BA surface treatment with octylsilane (OS) was negligible by contrast to alkylbenzene sulphonic acid (OS2). Like the tensile mechanical data, the essential and non-essential work of fracture parameters did not change significantly, either. Improved PCL/BA adhesion in case of OS2 treatment excluded the usual EWF treatise. This was circumvented by making use of energy partitioning between yielding and necking. The yielding related essential work of fracture decreased while the non-essential one increased with BA content and with better interfacial adhesion. This was attributed to the effect of matrix/filler debonding

Development and Characterization of Next-Generation Contact Materials for Nanoelectromechanical Switches

Nanoelectromechanical (NEM) switches were identified by the semiconductor industry as a low-power beyond CMOS technology. However, the reliability of the contact interface currently limits the commercialization of NEM switches, as the electrical contact has to be able to physically open and close up to a quadrillion (10^15) times without failing due to adhesion (by sticking shut) or contamination (reducing switch conductivity). These failure mechanisms are not well understood, and materials that exhibit the needed performance have not been demonstrated. Thus, commercially viable NEM switches demand the development of novel contact materials along with efficient methods to evaluate the performance of these materials. To assess contact material candidates under NEM switch-like conditions, we developed a novel, high-throughput electrical contact screening method based on atomic force microscopy (AFM) that enables billions of contact cycles in laboratory timeframes. We compared the performance of self-mated and dissimilar single asperity Pt and PtxSi contacts under forces and environments representative of NEM switch operation and cycled up to 10 million times. The contact resistance increased by up to three decades due to cycling-induced growth of insulating tribopolymer in the case of Pt-Pt contacts whereas PtxSi exhibited reduced tribopolymer formation. We also pursued the development of novel contact material candidates that are highly conductive, minimally adhesive, chemically inert, mechanically robust, and amenable to CMOS fabrication processes. One promising candidate material is platinum silicide (PtxSi). The controlled diffusion of thin films of amorphous silicon and platinum allowed us to tune the chemical composition of PtxSi over a wide range (

Selektionsvorteil von Kopf- und Halstumorzellen durch differenzielle Lokalisation und Expression von PD-L1 nach Radiatio

Tumoren im Kopf- und Halsbereich stellen mit über 630.000 Neuerkrankungen pro Jahr weltweit ein zentrales Thema in der Forschung dar. Trotz einer Vielzahl an Behandlungsmöglichkeiten wie ein chirurgischer Eingriff, Chemo-, Strahlen- oder eine Immuntherapie, konnte die Überlebensrate in den letzten Jahren nicht signifikant verbessert werden. Fraglich ist, weshalb die Heterogenität beim Ansprechen auf die Therapien so groß ist, die entarteten Zellen Behandlungen überleben können und bei bis zu 30 % der Patienten/-innen eine Hyperprogression auftritt. In der vorliegenden Arbeit wurde untersucht, in welchen Bestandteilen der radioresistenten und radiosensitiven Kopf- und Halstumorzelllinien der Programmed Death Ligand 1 vor und nach einer Bestrahlung vorkommt und ob dieser intrinsische Funktionen in den Tumorzellen erfüllen könnten. Dabei zeigte sich eine PD-L1 Expression auf der Membran aller Zelllinien. Nach einer Bestrahlung mit 8 Gy, konnte bei den radiosensitiven Krebszellen eine Abnahme der PD-L1 Expression auf der Zelloberfläche, bei den radioresistenten Zellen gegenläufig eine Zunahme der PD-L1 Expression an der Membran nachgewiesen werden. Gleichzeitig führte eine Radiatio zu einem Anstieg des zytoplasmatischen PD-L1 Gehalts und einem Abfall der nukleären PD-L1 Expression in radioresistenten Kopf- und Halstumorzelllinien. Weiterhin konnte festgestellt werden, dass der relative Anteil PD-L1 positiver Zellen nach einer Bestrahlung deutlich höher war als bei den unbestrahlten Kontrollzellen. Daneben wiesen die PD-L1 positiven Zellen eine veränderte Morphologie, welche sich durch eine vergrößerte und spindelförmige Gestalt der Krebszellen darstellte, auf. Zusammenfassend deuten die Ergebnisse darauf hin, dass intrazelluläres PD-L1 intrinsische Funktionen erfüllen könnte, welche den Tumorzellen einen bedeutenden Überlebensvorteil schaffen und eine Resistenz gegen Therapien vermitteln könnten

The educational effects of pre and post-work in out-of-school laboratories

Since the 1980’s, education had to face various challenges such as new technologies, new ways of information gathering but also a reconsideration of conventional educational approaches. As a result, more emphasis has been placed on laboratory work in school science. In many industry nations, this trend was likewise bolstered by unexpected poor results in international comparative assessments (e.g. PISA, TIMSS), as well as students’ poor perception of science and, in relation to that, negative effects on career choices. To combat this growing trend, in Germany many out-of-school science laboratories were established in the recent years to foster interest in science. However, despite their positive temporary effects, approaches to increase effects or to develop long term positive changes are in demand. This research investigates how the out-of-school laboratory effects are affected by a preparation and post enhancement based upon previous studies. Therefore, an online portal was developed which provided cognitive and affective content in order to prepare and post enhance students for their visit in an out-of-school laboratory. The research-based study was aimed at students from grade 10 of lower and upper secondary level who perform one-day experimental activities at the out-of-school laboratory located at the Helmholtz-Zentrum Dresden-Rossendorf research center. In doing so, a comparative analysis was conducted between students who used the online portal and control group members who just regularly visited the laboratory without a special preparation or post enhancement. The evaluation follows a pre, post, and follow-up approach. Based on the results of this research, it could be confirmed that the online portal, as a tool to prepare and post enhance students, had a significant impact. Moreso, students’ situational interest was positively promoted through the online portal. This also applied for related features, like students’ self-concept as well as their perceptions of the out-of-school laboratory environment and even slight effects on their individual interest. As it turned out regarding the desired situational interest, females benefitted most. However, again most results suggest that evoked effects diminish over time. Even though this likely can be traced back to the characteristics of the post enhancement of the online portal, outcomes regarding students’ interest in science and a career in physics indicate the post enhancement’s ability to ensure sustainability. Within the sample three classes were identified based on their interests. Accordingly, for all classes’ members the portal fosters their situational interest. This especially applies for less scientific interested students. Assessments on the portal’s perception by the students revealed a high degree of willingness to prepare for the laboratory visit and to spend the time required. A large majority appreciated the online portal for their laboratory work. An extended preparation, like presented in this study, is still regarded as acceptable to the students. Nevertheless, a compulsory preparation and post enhancement is highly recommended. On the whole, it can be concluded that the online portal respectively a preparation and post enhancement is beneficial for activities out-of-school.:1. Science, Education, & Society 2. Out-of-school laboratories 3. Out-of-school science education 4. Applied educational psychological concepts 5. Studies on out-of-school science laboratories 6. Research Questions and Hypotheses 7. Methods 8. The Study 9. Statistics 10. Determination of the student groups 11. Verification of the hypothesis 12. Investigations on the online portal 13. Discussion 14. Summary 15. Limitations of the study 16. Implications and recommendationsAnfang der 1980er-Jahre ergaben sich im Bildungssektor eine Reihe von Herausforderungen, die im Zusammenhang mit neuen Technologien, neuen Wegen des Informationsaustausches, aber auch des Hinterfragens traditioneller Bildungsansätze standen. Im Ergebnis dessen kam der experimentellen Arbeit im naturwissenschaftlichen Unterricht eine stärkere Rolle zu. Unerwartet schwache Ergebnisse internationaler Vergleichsstudien (z.B. PISA, TIMSS) sowie ein schlechtes Image der Naturwissenschaften und damit einhergehende negative Auswirkungen auf die Kurs- und Berufswahl verstärkten diesen Trend in vielen Industrienationen. Vor diesem Hintergrund und mit dem Ziel, Interesse an Naturwissenschaften zu fördern, wurden in Deutschland in den vergangenen Jahren zahlreiche Schülerlabore etabliert. Trotz der Tatsache, dass die Einrichtungen positive Effekte erzielen, sind diese teilweise gering oder schwächen mit der Zeit ab. Wie bisherige Studien vermuten lassen, scheint die Vor- und Nachbereitung von Veranstaltungen im Schülerlabor eine Lösung hierfür zu bieten. Anhand der vorgestellten Studie soll dies untersucht werden. In diesem Zusammenhang wurde ein Online-Portal für Schülerinnen und Schüler entwickelt. Basierend auf kognitiven und affektiven Inhalten bietet es Teilnehmern die Möglichkeit, ihren Schülerlaborbesuch vor- und nachzubereiten. Die Studie richtete sich an Schüler ab der 10. Klasse der Sekundarstufe 1 und 2, die einen Experimentiertag im Schülerlabor DeltaX am Helmholtz-Zentrum Dresden-Rossendorf absolvierten. Dabei wurden in Form einer Vergleichsstudie Teilnehmer mit und ohne Nutzung des Online-Portals gegenübergestellt. Die entsprechenden Daten der Untersuchung wurden durch eine Fragebogenerhebung im Pre-Post-Follow-up-Design erhoben. Die Ergebnisse der Studie bestätigen den signifikanten Einfluss des Online-Portals. So zeigen sich durchaus positive Effekte hinsichtlich der Entwicklung des aktuellen Interesses der Schülerinnen und Schüler. Gleiches gilt auch im Hinblick auf verwandte Konstrukte wie das Fähigkeitsselbstkonzept, die wahrgenommenen Merkmale der Laborumgebung und auch abgeschwächt für dispositionale Interessen. Bezogen auf die angestrebte Förderung des aktuellen Interesses zeigte sich, dass vor allem Schülerinnen profitieren. Allerdings ließ sich für die meisten der hervorgerufenen Effekte ein Absinken im Verlauf der Zeit erkennen. Möglicherweise ist das auf die Umsetzung der Nachbereitung im Rahmen des Online-Portals zurückzuführen. Die Ergebnisse lassen die Vermutung zu, dass die Nachbereitung bezüglich des Interesses an Naturwissenschaften und an einem physikalischen Beruf das Potenzial besitzt, mehr Nachhaltigkeit hervorzurufen. Um Vorinteressen der Teilnehmer zu berücksichtigen, konnten drei unterschiedliche naturwissenschaftliche Interessensklassen identifiziert werden. Es stellte sich heraus, dass die Entwicklung des aktuellen Interesses aller drei Interessenklassen durch das Online-Portal gefördert wird. Dies gilt vor allem für die gering naturwissenschaftlich interessierten Schülerinnen und Schüler. Untersuchungen, die sich auf das Online-Portal selbst bezogen, offenbarten zum einen ein hohes Maß an Bereitschaft, sich auch mit dem dafür notwendigen zeitlichen Aufwand auf den Experimentiertag im Schülerlabor vorzubereiten. Zum anderen schätzt die breite Mehrheit der Teilnehmer das Online-Portal für ihre Arbeit im Schülerlabor. Selbst eine umfangreichere Vorbereitung wird von den Schülerinnen und Schülern als akzeptabel betrachtet. Es wird dennoch dazu geraten, die Vor- und Nachbereitung obligatorisch durchzuführen. Insgesamt zeigen die Ergebnisse dieser Studie den positiven Einfluss des Online-Portals bzw. der Vor- und Nachbereitung auf außerschulische Aktivitäten.:1. Science, Education, & Society 2. Out-of-school laboratories 3. Out-of-school science education 4. Applied educational psychological concepts 5. Studies on out-of-school science laboratories 6. Research Questions and Hypotheses 7. Methods 8. The Study 9. Statistics 10. Determination of the student groups 11. Verification of the hypothesis 12. Investigations on the online portal 13. Discussion 14. Summary 15. Limitations of the study 16. Implications and recommendation

Significance of Apoptosis in the Process of Tumorigenesis in Colorectal Mucosa and Adenomas in FAP Patients

The relation between proliferation and apoptosis was studied in colorectal mucosal biopsies (N=41), tubular adenomas (TA) (N=104) and tubulovillous adenomas (TVA) (N=34) from 37 FAP patients. Proliferative activity was determined by cell cycle distribution analysis. In addition, transcriptional capacity was determined by chromatin in situ testing. For both, DNA flow cytometry was used. Cycling cells were identified by immunohistochemical staining with monoclonal antibody Ki67. The existence of subdiploid apoptotic cells was derived from DNA and/or DNA/protein patterns. In a follow‐up group, the mucosa is characterised by a balance between proliferation (S % + G2M % = 19) and apoptotic cells (% = 17). The percentage of Ki67 positive cells (16%) corresponds to the percentages mentioned above. In TA, the amount of apoptotic cells remains unaltered, in TVA it decreases to 8%. At the same time, the percentage of Ki67 positive cells increases significantly in both TA and TVA (39%, 42%). With patients who underwent surgery due to clinical signs without histological evidence for malignancy, apoptotic cells in TA continue to decrease significantly (9%), without any changes in cycling cells. Only in the carcinoma‐bearing bowel, cycling cells increase to 52%. Here, the percentage of apoptotic cells in TVA reaches the lowest level (5%). A connection between proliferation and apoptosis was observed in mucosa and TVA. The process of tumorigenesis is characterised by a stepwise increase in resistance to apoptosis followed by an increase in cycling cells