Treatment of non-muscle invasive bladder cancer with Bacillus Calmette–Guerin (BCG): Biological markers and simulation studies

AbstractIntravesical Bacillus Calmette–Guerin (BCG) vaccine is the preferred first line treatment for non-muscle invasive bladder carcinoma (NMIBC) in order to prevent recurrence and progression of cancer. There is ongoing need for the rational selection of i) BCG dose, ii) frequency of BCG administration along with iii) synergistic adjuvant therapy and iv) a reliable set of biochemical markers relevant to tumor response. In this review we evaluate cellular and molecular markers pertinent to the immunological response triggered by the BCG instillation and respective mathematical models of the treatment. Specific examples of markers include diverse immune cells, genetic polymorphisms, miRNAs, epigenetics, immunohistochemistry and molecular biology ‘beacons’ as exemplified by cell surface proteins, cytokines, signaling proteins and enzymes. We identified tumor associated macrophages (TAMs), human leukocyte antigen (HLA) class I, a combination of Ki-67/CK20, IL-2, IL-8 and IL-6/IL-10 ratio as the most promising markers for both pre-BCG and post-BCG treatment suitable for the simulation studies.The intricate and patient-specific nature of these data warrants the use of powerful multi-parametral mathematical methods in combination with molecular/cellular biology insight and clinical input

Effects for Efficiency: Asymptotic Speedup with First-Class Control

We study the fundamental efficiency of delimited control. Specifically, we show that effect handlers enable an asymptotic improvement in runtime complexity for a certain class of functions. We consider the generic count problem using a pure PCF-like base language $\lambda_b$ and its extension with effect handlers $\lambda_h$. We show that $\lambda_h$ admits an asymptotically more efficient implementation of generic count than any $\lambda_b$ implementation. We also show that this efficiency gap remains when $\lambda_b$ is extended with mutable state. To our knowledge this result is the first of its kind for control operators

Comparing Libraries for Generic Programming in Haskell

Datatype-generic programming is defining functions that depend on the structure, or ``shape\u27\u27, of datatypes. It has been around for more than 10 years, and a lot of progress has been made, in particular in the lazy functional programming language Haskell. There are more than 10 proposals for generic programming libraries or language extensions for Haskell. To compare and characterize the many generic programming libraries in a typed functional language, we introduce a set of criteria and develop a generic programming benchmark: a set of characteristic examples testing various facets of datatype-generic programming. We have implemented the benchmark for nine existing Haskell generic programming libraries and present the evaluation of the libraries. The comparison is useful for reaching a common standard for generic programming, but also for a programmer who has to choose a particular approach for datatype-generic programming. [Technical report version.

Comparing Libraries For Generic Programming In Haskell

Datatype-generic programming is defining functions that depend on the structure, or ``shape\u27\u27, of datatypes. It has been around for more than 10 years, and a lot of progress has been made, in particular in the lazy functional programming language Haskell. There are more than 10 proposals for generic programming libraries or language extensions for Haskell. To compare and characterize the many generic programming libraries in a typed functional language, we introduce a set of criteria and develop a generic programming benchmark: a set of characteristic examples testing various facets of datatype-generic programming. We have implemented the benchmark for nine existing Haskell generic programming libraries and present the evaluation of the libraries. The comparison is useful for reaching a common standard for generic programming, but also for a programmer who has to choose a particular approach for datatype-generic programming