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Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach (2013)

Wolfgang Jäger Igor Moskalev Claudia Janssen Tetsutaro Hayashi Shannon Awrey Kilian M. Gust Alan I. So Kaixin Zhang Ladan Fazli Estelle Li Joachim W. Thüroff Dirk Lange Peter C. Black

Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.

Evidence regarding clinical use of microvolt T-wave alternans (2011)

Stefan H. Hohnloser Takanori Ikeda Richard J. Cohen

Background: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. Objective: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. Methods: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (≤15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). Results: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. Conclusion: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD. Key words: Arrhythmia; Sudden cardiac death; Cardiac arrest; ICD; T-wave alternans; Surrogate endpoint; Ventricular tachyarrhythmic event; Primary prevention

'Kiezdeutsch goes School' : a multiethnic variety of German from an educational perspective (2008)

Kerstin Paul Ulrike Freywald Eva Wittenberg

This article presents linguistic features of and educational approaches to a new variety of German that has emerged in multi-ethnic urban areas in Germany: Kiezdeutsch (‘Hood German’). From a linguistic point of view, Kiezdeutsch is very interesting, as it is a multi-ethnolect that combines features of a youth language with those of a contact language. We will present examples that illustrate the grammatical productivity and innovative potential of this variety. From an educational perspective, Kiezdeutsch has also a high potential in many respects: school projects can help enrich intercultural communication and weaken derogatory attitudes. In grammar lessons, Kiezdeutsch can be a means to enhance linguistic competence by having the adolescents analyse their own language. Keywords: German, Kiezdeutsch, multi-ethnolect, migrants’ language, language change, educational proposals

The performance of approximating ordinary differential equations by neural nets (2008)

Josef Fojdl Rüdiger W. Brause

The dynamics of many systems are described by ordinary differential equations (ODE). Solving ODEs with standard methods (i.e. numerical integration) needs a high amount of computing time but only a small amount of storage memory. For some applications, e.g. short time weather forecast or real time robot control, long computation times are prohibitive. Is there a method which uses less computing time (but has drawbacks in other aspects, e.g. memory), so that the computation of ODEs gets faster? We will try to discuss this question for the assumption that the alternative computation method is a neural network which was trained on ODE dynamics and compare both methods using the same approximation error. This comparison is done with two different errors. First, we use the standard error that measures the difference between the approximation and the solution of the ODE which is hard to characterize. But in many cases, as for physics engines used in computer games, the shape of the approximation curve is important and not the exact values of the approximation. Therefore, we introduce a subjective error based on the Total Least Square Error (TLSE) which gives more consistent results. For the final performance comparison, we calculate the optimal resource usage for the neural network and evaluate it depending on the resolution of the interpolation points and the inter-point distance. Our conclusion gives a method to evaluate where neural nets are advantageous over numerical ODE integration and where this is not the case. Index Terms—ODE, neural nets, Euler method, approximation complexity, storage optimization.

Handwriting analysis for diagnosis and prognosis of Parkinson’s disease (2006)

Atilla Ünlü Rüdiger W. Brause Karsten Krakow

At present, there are no quantitative, objective methods for diagnosing the Parkinson disease. Existing methods of quantitative analysis by myograms suffer by inaccuracy and patient strain; electronic tablet analysis is limited to the visible drawing, not including the writing forces and hand movements. In our paper we show how handwriting analysis can be obtained by a new electronic pen and new features of the recorded signals. This gives good results for diagnostics. Keywords: Parkinson diagnosis, electronic pen, automatic handwriting analysis

On the scope of the referential hierarchy in the typology of grammatical relations (2008)

Balthasar Bickel

In the late seventies, Bernard Comrie was one of the first linguists to explore the effects of the referential hierarchy (RH) on the distribution of grammatical relations (GRs). The referential hierarchy is also known in the literature as the animacy, empathy or indexibability hierarchy and ranks speech act participants (i.e. first and second person) above third persons, animates above inanimates, or more topical referents above less topical referents. Depending on the language, the hierarchy is sometimes extended by analogy to rankings of possessors above possessees, singulars above plurals, or other notions. In his 1981 textbook, Comrie analyzed RH effects as explaining (a) differential case (or adposition) marking of transitive subject ("A") noun phrases in low RH positions (e.g. inanimate or third person) and of object ("P") noun phrases in high RH positions (e.g. animate or first or second person), and (b) hierarchical verb agreement coupled with a direct vs. inverse distinction, as in Algonquian (Comrie 1981: Chapter 6).

Prosodic tautomorphemicity in Sino-Tibetan (2003)

Balthasar Bickel

Sino-Tibetan is a prime example of how strongly a language family can typologically diversify under the pressure of areal spread features (Matisoff 1991, 1999). One of the manifestation of this is the average length of prosodic words. In Southeast Asia, prosodic words tend to average on one or one-and-a-half syllables. In the Himalayas, by contrast, it is not uncommon to encounter prosodic words containing five to ten syllables. The following pair of examples illustrates this.

Capturing particulars and universals in clause linkage: a multivariate analysis (2010)

Balthasar Bickel

Absolute and statistical universals (2007)

Balthasar Bickel

Language universals are statements that are true of all languages, for example: “all languages have stop consonants”. But beneath this simple definition lurks deep ambiguity, and this triggers misunderstanding in both interdisciplinary discourse and within linguistics itself. A core dimension of the ambiguity is captured by the opposition “absolute vs. statistical universal”, although the literature uses these terms in varied ways. Many textbooks draw the boundary between absolute and statistical according to whether a sample of languages contains exceptions to a universal. But the notion of an exception-free sample is not very revealing even if the sample contained all known languages: there is always a chance that an as yet undescribed language, or an unknown language from the past or future, will provide an exception.

Dulong texts : seven fully analyzed narrative and procedural texts (2001)

Randy J. LaPolla

Dulong is a Tibeto-Burman language spoken in Gongshan Dulong and Nu Autonomous county in Yunnan, China, by members of the Dulong nationality (pop.: 6,000), and part of the Nu nationality (roughly 6,000 people).

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