Lösungsverhalten von Schülerinnen und Schülern bei einfachen linearen Gleichungen: Eine empirische Untersuchung im 9. Schuljahr und eine Entwicklung eines kategoriellen Computerdiagnosesystems

Diese Dissertation widmet sich dem Bereich des Lösens von einfachen linearen Gleichungen, der in der Schulmathematik in der 7. und 8. Jahrgangsstufe systematisch behandelt wird. Die Arbeit besteht aus drei Teilen: einem Theorieteil, einer empirische Untersuchung und einer informatischen und mathematikdidaktischen Softwareentwicklung. Im Theorieteil werden die historische Entwicklung der Schulalgebra, die Anforderungen, die an die Schülerinnen und Schüler im Algebraunterricht gestellt werden und die damit verknüpften Lernschwierigkeiten dargestellt. Im zweiten Teil wird die empirische Untersuchung, die im Frühjahr 1997 in 56 Klassen (bzw. Kursen von Integrierten Gesamtschulen) der 9. Jahrgangsstufe mit 448 Schülerinnen und 416 Schüler durchgeführt wurde, einschliesslich erster Auswertungen und Ergebnisse beschrieben. Im dritten Teil wird die selbstentwickelte Software beschrieben, mit deren Hilfe es überhaupt erst möglich wurde, den Lösungsprozess der Schülerinnen und Schüler genauer zu analysieren. Die verschiedenen Auswertungen und Ergebnisse werden ausführlich dargelegt und zukünftige Perspektiven für den Mathematikunterricht aufgezeigt. Bei meiner empirischen Untersuchung folge ich forschungsmethodisch der deskriptiven Fehleranalyse und nutze Methoden der Künstlichen-Intelligenz-Forschung. Der Computer kommt auf dreierlei Art ins Spiel: Ein selbstentwickeltes Datenbanksystem ermöglicht die Ein- und Ausgabe der Testdaten. Ein dazu programmiertes Prologregelwerk übernimmt die erste Auswertung. Mit dem Standardsoftwarepaket SPSS wird die damit erzeugte Datenbank schließlich statistisch ausgewertet. Ziel dieser Arbeit ist es, einen Überblick über Schwierigkeitsgrade von Aufgaben, Fehlermuster bei Aufgaben und verwendete Strategien zum Lösen zu erhalten. Durch den Einsatz der selbstentwickelten Software wird es möglich, auch große Datenmengen zu untersuchen und zusätzlich zum Lösungsprodukt (den vorliegenden schriftlichen Schülerlösungen) auchThese thesis deal with the solving of simple linear equations. Solving equations is a discipline which is systematically taught in the 7th and 8th grade. The dissertation consists of three parts: a part of theory, an empirical study and a software development. The theoretical part describes the historic development of school algebra, the assignments for students in school algebra and the difficulties in this context. The second part describes the empirical study including analysis and results. This study is based on the data of 56 9th grade classes (448 female and 416 male students) and was ascertained in spring 1997. The third part consists of the description of the self-developed software which enabled me to evaluate the solving process performed by the students. The various analysis and results are described in detail and future perspectives for mathematical education are pointed out. My empirical study is based on the method of descriptive error-analysis. Perceptions of artifical intelligence research are used. The computer is used in three ways. A self-developed database system enables the in- and output of the test data. A Prolog-programmed system performs the first classification. The standard package SPSS does the final analysis on the data base. The aim of my empirical study is to attain an overview on the different levels of difficulty, to perform error analysis and to explain solving strategies. Using the self-developed system enables to analyse large databases and to perform the analysis of the solving process as well as the solving product. Furthermore, these thesis create a basis for further development of adaptive diagnosis systems and intelligent tutorial systems in the syntactic-algorithmical field of school mathematics

Health economic evaluation of moist wound care in chronic cutaneous leishmaniasis ulcers in Afghanistan

Background: The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major. Methods: A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan. Results: Average costs per patients were US$11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound treatment [MWT]) and US$25 (SE = 0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens’ drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33) in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of the cases starting at a willingness-to-pay of 80 cent per wound free day. Conclusions: Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure

THSD7A Positivity Is Associated with High Expression of FAK in Prostate Cancer

Prostate cancer is one of the most common malignancies, and there are a wide range of treatment options after diagnosis. Most prostate cancers behave in an indolent manner. However, a given sub-group has been shown to exhibit aggressive behavior; therefore, it is desirable to find novel prognostic and predictive (molecular) markers. THSD7A expression is significantly associated with unfavorable prognostic parameters in prostate cancer. FAK is overexpressed in several tumor types and is believed to play a role in tumor progression and metastasis. Furthermore, there is evidence that THSD7A might affect FAK-dependent signaling pathways. To examine whether THSD7A expression has an impact on the expression level of FAK in its unphosphorylated form, a total of 461 prostate cancers were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity and low FAK expression were associated with adverse pathological features. THSD7A positivity was significantly associated with high FAK expression. To our knowledge we are the first to show that THSD7A positivity is associated with high FAK expression in prostate cancer. This might be proof of the actual involvement of THSD7A in FAK-dependent signaling pathways. This is of special importance because THSD7A might also serve as a putative therapeutic target in cancer therapy

THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC

SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis “prostate cancer”. For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage (p < 0.001), positive nodal status (p < 0.001) and high Gleason-score (p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer

Diagnostic Performance of Kwak, EU, ACR, and Korean TIRADS as Well as ATA Guidelines for the Ultrasound Risk Stratification of Non-Autonomously Functioning Thyroid Nodules in a Region with Long History of Iodine Deficiency: A German Multicenter Trial

Simple Summary In Germany, thyroid nodules can be detected by ultrasound examinations in over 30% of the adult population, mainly as a result of prolonged nutritive iodine deficiency. Although only a small proportion of the nodules are malignant, it is important to have a reliable examination method that not only can detect these few thyroid carcinomas with a high degree of certainty, but also not be unnecessarily invasive for the much larger number of benign nodules. Ultrasound is the method of choice, and ultrasound-based risk stratification systems are important tools in clinical care. However, many different systems have been introduced within the last decade. The aim of this study was to evaluate five common ultrasound risk stratification systems for their diagnostic accuracy of thyroid nodules from an area with long history of iodine deficiency. Abstract Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30% of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency

A randomized controlled phase IIb wound healing trial of cutaneous leishmaniasis ulcers with 0.045% pharmaceutical chlorite (DAC N-055) with and without bipolar high frequency electro-cauterization versus intralesional antimony in Afghanistan

Background: A previously published proof of principle phase IIa trial with 113 patients from Kabul showed that bipolar high-frequency (HF) electro-cauterization (EC) of cutaneous leishmaniasis (CL) ulcers and subsequent moist wound treatment (MWT) closed 85% of all Leishmania (L.) tropica lesions within 60 days. Methods: A three-armed phase IIb, randomized and controlled clinical trial was performed in Mazar-e-Sharif. L. tropica- or L. major-infected CL patients received intradermal sodium stibogluconate (SSG) (Group I); HF-EC followed by MWT with 0.045% DAC N-055 (Group II); or MWT with 0.045% DAC N-055 in basic crème alone (Group III). The primary outcome was complete epithelialisation before day 75 after treatment start. Results: 87 patients enrolled in the trial were randomized into group I (n = 24), II (n = 32) and III (n = 31). The per-protocol analysis of 69 (79%) patients revealed complete epithelialisation before day 75 in 15 (of 23; 65%) patients of Group I, in 23 (of 23; 100%) patients of Group II, and in 20 (of 23; 87%) patients of Group III (p = 0.004, Fisher’s Exact Test). In the per-protocol analysis, wound closure times were significantly different between all regimens in a pair-wise comparison (p = 0.000039, Log-Rank (Mantel-Cox) test). In the intention-to-treat analysis wound survival times in Group II were significantly different from those in Group I (p = 0.000040, Log-Rank (Mantel-Cox) test). Re-ulcerations occurred in four (17%), three (13%) and seven (30%) patients of Group I, II or III, respectively (p = 0.312, Pearson Chi-Square Test). Conclusions: Treatment of CL ulcers with bipolar HF-EC followed by MWT with 0.045% DAC N-055 or with DAC N-055 alone showed shorter wound closure times than with the standard SSG therapy. The results merit further exploration in larger trials in the light of our current knowledge of in vitro and in vivo activities of chlorite. Clinicaltrials.gov ID: NCT00996463. Registered: 15th October 2009

Routine implementation costs of larviciding with Bacillus thuringiensis israelensis against malaria vectors in a district in rural Burkina Faso

Background: The key tools in malaria control are early diagnosis and treatment of cases as well as vector control. Current strategies for malaria vector control in sub-Saharan Africa are largely based on long-lasting insecticide-treated nets (LLINs) and to a much smaller extent on indoor residual spraying (IRS). An additional tool in the fight against malaria vectors, larval source management (LSM), has not been used in sub-Saharan Africa on a wider scale since the abandonment of environmental spraying of DDT. Increasing concerns about limitations of LLINs and IRS and encouraging results from large larvicide-based LSM trials make a strong case for using biological larviciding as a complementary tool to existing control measures. Arguments that are often quoted against such a combined approach are the alleged high implementation costs of LSM. This study makes the first step to test this argument. The implementation costs of larval source management based on Bacillus thuringiensis israelensis (Bti) (strain AM65-52) spraying under different implementation scenarios were analysed in a rural health district in Burkina Faso. Methods: The analysis draws on detailed cost data gathered during a large-scale LSM intervention between 2013 and 2015. All 127 villages in the study setup were assigned to two treatment arms and one control group. Treatment either implied exhaustive spraying of all available water collections or targeted spraying of the 50 % most productive larval sources via remote-sensing derived and entomologically validated risk maps. Based on the cost reports from both intervention arms, the per capita programme costs were calculated under the assumption of covering the whole district with either intervention scenario. Cost calculations have been generalized by providing an adaptable cost formula. In addition, this study assesses the sensitivity of per capita programme costs with respect to changes in the underlying cost components. Results: The average annual per capita costs of exhaustive larviciding with Bti during the main malaria transmission period (June–October) in the Nouna health district were calculated to be US$1.05. When targeted spraying of the 50$ 0.77. Additionally, a high sensitivity of per capita programme costs against changes in total surface of potential larval sources and the number of spraying repetitions was found. Discussion: The per capita costs for larval source management interventions with Bti are roughly a third of the annual per capita expenditures for anti-malarial drugs and those for LLINs in Burkina Faso which are US$ 3.80 and 3.00, respectively. The average LSM costs compare to those of IRS and LLINs for sub-Saharan Africa. The authors argue that in such a setting LSM based on Bti spraying is within the range of affordable anti-malarial strategies and, consequently, should deserve more attention in practice. Future research includes a cost-benefit calculation, based on entomological and epidemiological data collected during the research project

Alternative splicing regulates stochastic NLRP3 activity

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3. exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity