Array programming with NumPy.

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.

Bone marrow disease in rhabdomyosarcoma visualized by 2-[18F]fluorodeoxyglucose positron emission tomography/computed tomography.

Bone marrow metastases-noted in 6% of patients with rhabdomyosarcoma-have been linked to very poor outcomes. Bilateral bone marrow sampling from iliac crests has been the gold standard for bone marrow examination in rhabdomyosarcoma, but sampling errors due to patchy bone marrow involvement may limit its sensitivity. Here, we report the case of a 6-year-old boy with embryonal rhabdomyosarcoma of the skull base and multiple 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG)-avid bone marrow metastases visualized by positron emission tomography and computed tomography (2-[18F]FDG PET/CT). His bone marrow aspirates were tumor-free. This case illustrates the diagnostic value of 2-[18F]FDG PET/CT in the detection of bone marrow metastases in rhabdomyosarcoma patients, which may re-shape the definition of bone marrow disease and, ultimately, alter disease staging and risk stratification.

An Empirical Survey on the Adaption of Neoadjuvant Chemotherapy in Bladder Cancer.

INTRODUCTION: The aim of the study was to determine the adaption of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) in Germany, Austria, and Switzerland and especially underlying reasons for potential low adherence to guidelines. METHODS: We conducted a non-validated survey among 336 urologic departments in Germany, Austria, and Switzerland. RedCap questionnaires were electronically distributed and included 23 items concerning the general NAC administration standards and guideline compliance in patient counseling regarding the actual treatment. RESULTS: The return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as the standard of care, only 49% of eligible patients actually receive NAC. An advanced disease stage (≥cT3) and a high tumor volume were mentioned to support the application of NAC, whereas 35% of responders worry about deterioration of patients' preoperative status due to NAC. Furthermore, 26.7% of respondents are concerned about the low extent of survival benefit. CONCLUSION: Application of NAC in eligible MIBC patients in Germany, Austria, and Switzerland remains low. Although the majority of urologic departments discuss NAC and acknowledge the need for intensified treatment in advanced disease stages, not all eligible patients will actually receive NAC before radical cystectomy.

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

OBJECTIVES: To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. PATIENTS AND METHODS: In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. RESULTS: Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR: 91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). CONCLUSION: Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Prospective evaluation of return to work, health-related quality of life and psychosocial distress after radical cystectomy: 1-year follow-up in 230 employed German bladder cancer patients.

PURPOSE: To evaluate return to work (RTW), health-related quality of life (HRQoL) and psychosocial distress (PD) after radical cystectomy (RC) and creation of an ileal conduit (IC) or an orthotopic ileal neobladder (NB) for bladder cancer. METHODS: The study relied on prospectively collected data for 842 patients, who underwent 3 weeks of inpatient rehabilitation (IR) after surgery between April 2018 and December 2019. HRQoL (EORTC QLQ-C30) and PD (Questionnaire on Stress in Cancer Patients [QSC-R10]) were evaluated at the beginning (T1) and end (T2) of IR as well as both 6 (T3) and 12 months after surgery (T4). Regression analyses were performed to identify predictors of HRQoL and RTW, respectively. RESULTS: Two hundred thirty patients (IC n = 51, NB n = 179) were employed before surgery (27.3%). HRQoL improved steadily, while high PD was present in 51.0% of patients at T4. RTW rate was 86.8 and 80.6% at T3 and T4, respectively. Linear regression analysis identified RTW as the only predictor for better HRQoL at T4 (OR [odds ratio] 12.823, 95% CI [confidence interval] 2.927-22.720, p = 0.012). Multivariate regression analysis identified age ≤ 59 years (OR 7.842; 95% CI 2.495-24.645; p < 0.001) as an independent positive predictor and lymph node metastasis (OR 0.220; 95% CI 0.054-0.893; p = 0.034) as an independent negative predictor of RTW at T4. CONCLUSION: Global HRQoL improved steadily during the follow-up and RTW rates are high. However, patients often reported high PD, reflecting a need for additional psychosocial support within aftercare.

Avoiding Prostate Biopsies in Patients at Low Risk for Prostate Cancer: A Prospective Evaluation of a PSA-Density-Based Safety Net.

INTRODUCTION AND OBJECTIVES: Decision-making to perform prostate biopsy should include individual risk assessment. Patients classified as low risk by the Rotterdam Prostate Cancer Risk Calculator are advised to forego biopsy (PBx). There is concern about missing clinically significant prostate cancer (csPCa). A clear pathway for follow-up is needed. MATERIAL AND METHODS: Data for 111 consecutive patients were collected. Patients were encouraged to adhere to a PSA-density-based safety net after PBx was omitted. Cut off values indicating a re-evaluation were PSA density >0.15 ng/mL/ccm in PBx-naïve patients and >0.2 ng/mL/ccm in men with past-PBx. Primary endpoint was whether men had their PSA taken regularly. Secondary endpoint was whether a new multiparametric MRI was performed when PSA-density increased. Tertiary endpoint was whether biopsy was performed when risk stratification revealed an increased risk. RESULTS: Median follow-up was 12 months (IQR 9-15 months). The primary endpoint was reached by 97.2% (n = 106). The secondary endpoint was reached by 30% (n = 3). The tertiary endpoint was reached by 50% (n = 2). Histopathologic analyses revealed csPCa in none of these cases. Risk stratification did not change (p = 0.187) with the majority of patients (89.2%, n = 99). CONCLUSION: The concern of missing csPCa when omitting PBx in the risk-stratified pathway may be negated. Changes in risk stratification during follow-up should lead to subsequent PBx. We suggest implementing a safety net based on PSA density and digital rectal examination (DRE).

Comparison of prostate cancer detection rates in patients undergoing MRI/TRUS fusion prostate biopsy with two different software-based systems.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy is a routinely used diagnostic tool for prostate cancer (PCa) detection. However, a clear superiority of the optimal approach for software-based MRI processing during biopsy procedures is still unanswered. To investigate the impact of robotic approach and software-based image processing (rigid vs. elastic) during MRI/transrectal ultrasound (TRUS) fusion prostate biopsy (FBx) on overall and clinically significant (cs) PCa detection. METHODS: The study relied on the instructional retrospective biopsy data collected data between September 2013 and August 2017. Overall, 241 men with at least one suspicious lesion (PI-RADS ≥ 3) on multiparametric MRI underwent FBx. The study protocol contains a systematic 12-core sextant biopsy plus 2 cores per targeted lesion. One experienced urologist performed 1048 targeted biopsy cores; 467 (45%) cores were obtained using rigid processing, while the remaining 581 (55%) cores relied on elastic image processing. CsPCa was defined as International Society of Urological Pathology (ISUP) grade ≥ 2. The effect of rigid versus elastic FBx on overall and csPCa detection rates was determined. Propensity score weighting and multivariable regression models were used to account for potential biases inherent to the retrospective study design. RESULTS: In multivariable regression analyses, age, prostate-specific antigen (PSA), and PIRADS ≥ 3 lesion were related to higher odds of finding csPCa. Elastic software-based image processing was independently associated with a higher overall PCa (odds ratio [OR] = 3.6 [2.2-6.1], p < 0.001) and csPCa (OR = 4.8 [2.6-8.8], p < 0.001) detection, respectively. CONCLUSIONS: Contrary to existing literature, our results suggest that the robotic-driven software registration with elastic fusion might have a substantial effect on PCa detection.

Psychosocial Distress in the Early Recovery Period after Radical Prostatectomy.

PURPOSE: This study aimed to evaluate psychosocial distress in the context of continence and oncological outcome during the early recovery period after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: Retrospectively collected data from 587 patients who underwent inpatient rehabilitation after RP in 2016 and 2017 were analyzed. Psychosocial distress (measured by using a Questionnaire on Stress in Cancer Patients [QSC-R10]) and continence status (urine loss on a 24-h pad test and urine volume on uroflowmetry) were evaluated at the beginning (T1) and end (T2) of a 3-week inpatient rehabilitation. Multivariate logistic regression was performed to identify predictors for high distress (QSC-R10 score ≥15). RESULTS: The median patient age was 65 years. At the start of rehabilitation, 204 patients (34.8%) demonstrated high distress. Psychosocial distress decreased significantly (p < 0.001) from a median of 11.0 at T1 (median 16 days after surgery) to a median of 6.0 at T2 (median 37 days after surgery). Complete continence increased significantly (p < 0.001) from 39.0% at T1 to 58.9% at T2. The median urine volume increased significantly (p < 0.001) from 161 mL at T1 to 230 mL at T2. Often, distress is higher in younger patients, whereas incontinence is higher in older patients. Multivariate logistic regression analysis identified age ≤69 years (p = 0.001) and tumor stage ≥pT3 (p = 0.006) as independent predictors of high distress. CONCLUSIONS: Distress and incontinence decreased significantly during the 3 weeks of inpatient rehabilitation after RP. Patient age ≤69 years and tumor stage ≥pT3 are independent predictors of high psychosocial distress.

How Many Cores Should Be Sampled during Systematic Prostate Biopsy in Case of Negative Multiparametric Magnetic Resonance Imaging? Analysis of 274 Men with Clinical Suspicion of Prostate Cancer.

INTRODUCTION: This study aimed to investigate the number of cores needed in a systematic biopsy (SB) in men with clinical suspicion of prostate cancer (PCa) but negative prebiopsy multiparametric magnetic resonance imaging and to test prostate-specific antigen (PSA) density as an indicator for reduced SB. METHODS: Two hundred and seventy-four patients were analyzed, extracted from an institutional database. Detection rates of any PCa and clinically significant (CS) PCa for different reduced biopsy protocols were compared by using Fisher's exact test. RESULTS: In total, 12-core SB revealed PCa in 103 (37.6%) men. Detection rates of reduced biopsy protocols were 74 (27%, 6-core) and 82 (29.9%, 8-core). Regarding CSPCa, 12-core SB revealed a detection rate of 26 (9.5%). Reduced biopsy protocols detected less CSPCa: 15 (5.5%) and 18 (6.6%), respectively. All differences were statistically significant, p < 0.05. PSA density ≥0.15 did not help to filter out men in whom a reduced biopsy may be sufficient. CONCLUSIONS: Twelve-core SB still has the highest detection rate of any PCa and CSPCa compared to reduced biopsy protocols. If the investigator and patient agree - based on individual risk calculation - to perform a biopsy, this SB should contain at least 12 cores regardless of PSA density.

Early continence after ileal neobladder: objective data from inpatient rehabilitation.

PURPOSE: To evaluate early continence of patients who underwent inpatient rehabilitation after radical cystectomy (RC) and orthotopic bladder substitution (ONB). METHODS: We conducted a retrospective analysis on the data of 283 patients who underwent a three weeks inpatient rehabilitation after RC and ONB for bladder cancer between January 2016 and July 2017. All patients were treated with a special multimodal continence therapy. The continence status was evaluated by measuring urine loss by a 24-h pad test and urine volume on uroflowmetry at the beginning (T1) and at the end (T2) of inpatient rehabilitation. Multivariate linear regression analysis was performed to identify independent predictors of urine loss. RESULTS: Median patient age was 63 years. NS was documented for 142 patients (50.2%). Median urine loss decreased significantly (p < 0.001) in the 24-h pad test, from 442 gm at T1 (median 29 days after surgery) to 88 gm at T2 (median 50 days after surgery). Urine volume increased significantly (p < 0.001) from a median of 78 ml at T1 to a median of 157 ml at T2. Age (p = 0.002), diabetes (p = 0.031), obesity (p = 0.003), and nerve sparing (p = 0.011) were identified as independent predictors for urine loss at the end of inpatient rehabilitation. CONCLUSION: Continence improved significantly during the three weeks of inpatient rehabilitation. Younger age, the absence of diabetes or obesity, and NS resulted in better continence in the early postoperative period after ONB.

Probability of Prostate Cancer Diagnosis following Negative Systematic and Targeted MRI: Transrectal Ultrasound Fusion Biopsy: A Real-Life Observational Study.

INTRODUCTION: The risk of occult prostate carcinoma (PCa) after negative multiparametric MRI (mpMRI)-transrectal fusion biopsy (F-Bx) is unknown. To determine the false-negative predictive value, we examined PCa detection after prior negative F-Bx. METHODS: Between December 2012 and November 2016, 491 patients with suspected PCa and suspicious mpMRI findings underwent transrectal F-Bx. Patients with benign pathology (n = 191) were eligible for our follow-up (FU) survey. Patient characteristics and clinical parameters were correlated to subsequent findings of newly detected PCa. RESULTS: Complete FU with a median of 31 (interquartile range: 17-39) months was available for 176/191 (92.2%) patients. Of those, 54 men had either surgical interventions on the prostate or re-Bxs. Newly detected PCa was evident in 14/176 (7.95%) patients stratified to ISUP ≤2 in 10 and ≥3 in 4 cases. The comparison of patients with newly detected PCa to those without cancerous findings in FU showed significant differences in prostate-specific antigen (PSA) density (0.16 vs. 0.13 ng/mL2) and prostate volume (45 vs. 67 mL, both p < 0.05). Both factors are significant predictors for newly detected cancer after initial negative F-Bx. CONCLUSION: Only PSA density (>0.13 ng/mL2) and small prostate volume are significant predictors for newly detected PCa after initial negative F-Bx. Despite negative mpMRI/TRUS F-Bx results, patients should be further monitored due to a risk of developing PCa over time. Notwithstanding the limitation of our study that not all patients underwent another Bx, we assume that the false-negative rate is low but existing. Our data represent a real-world scenario.

[Pediatric bone marrow alterations]. / Knochenmarkveränderungen am kindlichen Skelett.

The age-dependent development of the bone marrow follows a constant pattern and has an impact on the localization and morphology of various bone marrow processes. Physiological, reactive and benign bone marrow alterations must be differentiated from inflammatory or malignant infiltrations. In many cases, a specific age distribution pattern and typical morphological characteristics in magnetic resonance imaging (MRI) enable a diagnostic classification. The only adequate imaging modality that can provide information about the bone marrow composition is MRI.

Institutional Adoption and Apprenticeship of Fusion Targeted Prostate Biopsy: Does Experience Affect the Cancer Detection Rate?

INTRODUCTION: There are limited data on the learning curve of magnetic resonance imaging/transrectal ultrasound (MRI/TRUS)-fusion targeted prostate biopsies (tBx). OBJECTIVE: The aim of this study was to investigate the difference in prostate cancer (PCa) detection rate between an experienced urologist and novice resident performing tBx. METHODS: A total of 183 patients underwent tBx from 2012 to 2016 for a total of 518 tBx cores. Biopsies in this study were performed by an experienced urologist (investigator A) or a novice resident (investigator B). The outcome was the detection of PCa on tBx. Using a multivariable logistic regression model, we estimated odds ratios for the detection of PCa. Inverse probability treatment weighting (IPTW) was used to balance patients' baseline characteristics and compare detection rates of PCa. Before performance of tBx, all patients underwent MRI. RESULTS: On multivariable logistic regression analysis, investigator experience was associated with a higher odds of detection of PCa (OR = 1.003; 95% confidence interval 1.002-1.006, p = 0.037). After IPTW adjustment, there was no significant difference between the detection rate of investigator A (23%) and investigator B (32%; p = 0.457). CONCLUSIONS: Data revealed a positive association between investigator experience and the odds of PCa detection, although there was no difference in the detection rates of the investigators.

Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter?

BACKGROUND: The use of adjuvant chemotherapy (AC) in pure urothelial carcinoma of the bladder is established. Regarding variant histology, there is a gap in knowledge concerning the optimal treatment after radical cystectomy (RC). The objective of this study was to assess the effect of AC on overall survival (OS) in patients who had pure urothelial carcinoma, urothelial carcinoma with concomitant variant histology, or another pure variant histology. METHODS: Within the National Cancer Data Base, 15,397 patients who underwent RC for nonmetastatic, localized carcinoma of the bladder and had positive lymph nodes (T2N+) or locally advanced stage (≥T3N0/N+) were identified, excluding those who had previously received neoadjuvant chemotherapy. Multivariable Cox regression models were used to examine the specific effect of AC on OS stratified by each distinct histologic subtype, including pure urothelial carcinoma, micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. To account for immortal time bias, Cox regression analyses and Kaplan-Meier analyses were conducted with a landmark at 3 months. RESULTS: In multivariable landmark analyses, AC compared with initial observation was associated with an OS benefit for patients who had pure urothelial carcinoma (hazard ratio, 0.87; 95% confidence interval, 0.82-0.91), whereas no differences were observed with regard to those who had variant histology. CONCLUSIONS: Multivariable Cox regression landmark analysis revealed a survival benefit from AC for patients with a pure urothelial carcinoma. However, a survival benefit of AC for patients who had urothelial carcinoma with concomitant variant histology or other pure variant histology was not demonstrated.

Impact of tumor, treatment, and access on outcomes in bladder cancer: Can equal access overcome race-based differences in survival?

BACKGROUND: There are race-based differences in bladder cancer survival. To better understand this phenomenon, this study was designed to assess the statistical contributions of tumor, treatment, and access variables to race-based differences in survival. METHODS: Data were extracted from the National Cancer Data Base on black and white adults with muscle-invasive bladder cancer from 2004 to 2015. The impact of tumor, access, and treatment variables on differences in survival was inferred by the performance of sequential propensity score-weighted analyses in which black and white patients were balanced with respect to demographics and health status (comorbidities) tumor characteristics, treatment, and access-related variables. The propensity score-weighted hazard of death (black vs white) was calculated after each iteration. RESULTS: This study identified 44,577 patients with a median follow-up of 77 months. After demographics and health status were balanced, black race was associated with 18% worse mortality (hazard ratio, 1.18; 95% confidence interval [CI], 1.12-1.25; P < .001). Balancing by tumor characteristics reduced this to 16%, balancing by treatment reduced this to 10%, and balancing by access-related variables resulted in no difference. Access-related variables explained 40% (95% CI, 22.9%-57.0%) of the excess risk of death in blacks, whereas treatment factors explained 35% (95% CI, 22.2%-46.9%). The contribution of tumor characteristics was not significant. CONCLUSIONS: In the models, differences in survival for black and white patients with bladder cancer are best explained by disparities in access and treatment, not tumor characteristics. Access to care is likely a key factor in racial disparities in cancer.

Quality of Care in the Treatment of Localized Intermediate and High Risk Prostate Cancer at Minority Serving Hospitals.

PURPOSE: We investigated the quality of care at minority serving hospitals compared to other institutions for men with localized intermediate and high risk prostate cancer. MATERIALS AND METHODS: Using the National Cancer Database we identified 536,539 men 40 years old or older who presented with localized intermediate and high risk prostate cancer in the United States between 2004 and 2015. Institutions were ranked according to the proportion of black and Hispanic patients treated at a given institution, and the top decile institutions were defined as minority serving hospitals. We used multivariable analyses to characterize the association between minority serving hospitals and 3 end points, including receipt of definitive treatment, time to definitive treatment and receipt of androgen deprivation therapy in young (65 years or younger) and healthy (no comorbidity) men treated with external beam radiation therapy. RESULTS: A total of 162 and 1,168 hospitals were defined as minority and nonminority serving hospitals, respectively. On multivariable analyses treatment at minority serving hospitals was associated with decreased odds of receiving definitive treatment (adjusted OR 0.73, 95% CI 0.62-0.85, p <0.001). Adjusted mean ± SE time to treatment was significantly longer at minority serving hospitals compared to nonminority serving hospitals (4.9 ± 2.2 days, p = 0.024). Among young and healthy men there was no association between treatment at a minority serving hospital and receipt of androgen deprivation therapy in conjunction with external beam radiation (AOR 0.90, 95% CI 0.75-1.09, p = 0.291). CONCLUSIONS: Treatment at a minority serving hospital was associated with lower odds of receiving definitive therapy and longer time to definitive therapy for localized intermediate and high risk prostate cancer despite adjustment for race. This suggests that some racial disparities in prostate cancer may be explained by the sites at which racial and/or ethnic minorities receive care.

Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era.

INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the "pre-immunotherapy era") and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC. RESULTS: There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013. CONCLUSION: Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.

Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium.

Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

Dynamic reactions of liposomes.

Dynamic chemical reactions at the surface of liposomes are of fundamental interest to the understanding of physiological processes at biological membranes and can be exploited to prepare responsive soft materials. In this paper we describe a covalent yet reversible reaction between liposomes. To this end we explored the reversible thioester exchange reaction of membrane embedded amphiphilic thioesters with dithiols from solution. It was found that thioester exchange leads to the formation of covalent inter-liposomal cross-links and aggregation of liposomes. Liposome aggregation has a characteristic lag phase and the rate of aggregation depends on the concentration of dithiols as well as on the concentration of liposomes in solution. The reversibility of the aggregation could be demonstrated by dissociation of the liposome clusters by the addition of a monothiol. Furthermore we developed a fluorescence anisotropy assay to monitor the thioester exchange reaction on the membrane surface. To the best of our knowledge, the formation of a dynamic covalent network of liposomes is unprecedented.