The separation problem for regular languages by piecewise testable languages

Separation is a classical problem in mathematics and computer science. It asks whether, given two sets belonging to some class, it is possible to separate them by another set of a smaller class. We present and discuss the separation problem for regular languages. We then give a direct polynomial time algorithm to check whether two given regular languages are separable by a piecewise testable language, that is, whether a $B{\Sigma}1(<)$ sentence can witness that the languages are indeed disjoint. The proof is a reformulation and a refinement of an algebraic argument already given by Almeida and the second author

The Terracotta ‘Enthroned Goddess’ of Sicily

Terracotta statuettes were a popular ex-voto in Greek antiquity, varying in size and design. The use of a mold for terracotta figurines was introduced by Greek colonists in the 7th century B.C. to the indigenous people of Sicily. From that moment onwards there was an ongoing interaction between the cultic expressions of these different peoples, which reflected the changed social structures and the production and economic values of votive terracottas. This reciprocal interaction is visible in ..

Depressive and psychotic symptoms in schizophrenia:Focus on networks and treatment

This thesis has two main aims. First, to review and increase knowledge concerning symptom interaction in patients with schizophrenia, with a specific focus on co-occurring depressive symptoms and its neural correlates in major depressive disorder (Part I and II). Second, to review and investigate different treatment aspects and outcomes in schizophrenia (quality of life, depressive symptoms and mortality) (Part III). In sum, both network studies showed the importance of depressive symptoms in the symptom networks of patients with schizophrenia and showed the stability of such a network structure. Although the network approaches has several issues of debate, it is a promising new way of thinking about psychopathology. The network approach is an example of a new conceptualisation of psychopathology as dynamic systems that change over time. Additionally, this view on mental illness facilitates a more transdiagnostic approach, in which emotion regulation should be an important target for future studies. Given the frequent co-occurrence of depressive symptoms in patients with schizophrenia, its centrality, its correlations with suicidality and influence on quality of life, it is highly important to adequately treat co-occurring depressive symptoms and episodes. Systematically following the provided treatment guide to treat depressive symptoms or episodes might be useful. Additionally, meta-analyses showed that schizophrenia patients who do not use antipsychotics have a higher mortality risk compared to patients that use antipsychotics. In a similar way, continuous use of clozapine was related to a lower mortality risk compared to patients using other antipsychotics

Genetic Adaptation and Welfare

Beilharz says: The evolutionary processes, if they are not obstructed or misdirected, must lead to such a degree of adaptation that welfare will have to be taken for granted, just as we can do no better than to take for granted the welfare of any wild animal in its natural habitat. From this statement, one might conclude all we have to do is wait, and the animals will eventually adapt to intensive systems. Concerning animals put into new kinds of environments, he states that, if individuals do not have the capacity to adjust phenotypically, adaptation of the population will require a rapid genetic response to prevent dying out of the population. This comment may suggest that one does not have to wait very long for the animals to adapt successfully to intensive systems. He also notes that it is likely that a rapid genetic response is accompanied by much suffering. From this, one might conclude that suffering during such a process is only natural, and is therefore justified. Beilharz writes further that the procedure of adaptation may have to be approached in stages, if the environmental conditions aimed at are radically different from those to which the animals are now adapted. Because he fails to tell us whether intensive husbandry systems belong in this last category of environmental conditions, one might conclude that it is not necessary to adapt animals in stages if they are to be kept under intensive conditions. Therefore, because these statements of Beilharz could be misused to defend the practice of keeping animals under the stress of intensive conditions, under the rationalization that this is part of a long-term rational plan, I want to discuss each of these statements in the following comment

Genetic Adaptation and Welfare

Van Rooijen comments on Beilharz’s suggestion (IJSAP 3(2), 117) that it may be possible to adapt domestic animals to existing husbandry systems rather than adapt the systems to the animals. For example, Beilharz cites Tschanz, who has written that the best measurement of adaptation to an environment is reproduction. Van Rooijen provides an example of two bulls – one living freely with a group of cows and one used as a sperm donor, where welfare and reproductive success are not necessarily in harmony. He concludes that the evolutionary fitness and welfare of farm animals do not necessarily coincid

Genetic Adaptation and Welfare

Beilharz says: The evolutionary processes, if they are not obstructed or misdirected, must lead to such a degree of adaptation that welfare will have to be taken for granted, just as we can do no better than to take for granted the welfare of any wild animal in its natural habitat. From this statement, one might conclude all we have to do is wait, and the animals will eventually adapt to intensive systems. Concerning animals put into new kinds of environments, he states that, if individuals do not have the capacity to adjust phenotypically, adaptation of the population will require a rapid genetic response to prevent dying out of the population. This comment may suggest that one does not have to wait very long for the animals to adapt successfully to intensive systems. He also notes that it is likely that a rapid genetic response is accompanied by much suffering. From this, one might conclude that suffering during such a process is only natural, and is therefore justified. Beilharz writes further that the procedure of adaptation may have to be approached in stages, if the environmental conditions aimed at are radically different from those to which the animals are now adapted. Because he fails to tell us whether intensive husbandry systems belong in this last category of environmental conditions, one might conclude that it is not necessary to adapt animals in stages if they are to be kept under intensive conditions. Therefore, because these statements of Beilharz could be misused to defend the practice of keeping animals under the stress of intensive conditions, under the rationalization that this is part of a long-term rational plan, I want to discuss each of these statements in the following comment

Optimizing systemic therapy in metastatic breast cancer:implementation in daily practice and exploration of new drug targets

This thesis aims to study several aspects regarding metastatic breast cancer treatment. Approximately 15% of breast cancers express the HER2 receptor. This HER2 positivity makes it possible to treat patients with trastuzumab. Trastuzumab is a monoclonal antibody directed against HER2. Treatment and survival characteristics of patients with HER2 positive metastatic breast cancer are studied. Data of patients in the northern part of the Netherlands who have been treated with trastuzumab for metastatic breast cancer are collected by the Netherlands Cancer Registry. Tumor material of the primary breast tumors are also collected. The HER2 status has been determined using the most recent diagnostic criteria. Most of the tumors are indeed HER2 positive. It seems to be cost-effective to use a confirming diagnostic test in tumors of patients who are tested HER2 positive with the standard diagnostic test. This will also reduce the number of patients who are unfairly treated with trastuzumab. Most of the selected patients have been treated with the registered combination of trastuzumab with chemotherapy. Survival of these patients is comparable with the survival found in the previous conducted clinical trials. A limited number of patients has been treated with trastuzumab and vinorelbine containing chemotherapy. This combination was not registered for this indication, however eventually this combination has also been proven effective. Furthermore the interaction between the androgen receptor and the immune microenvironment in HER2 positive breast tumors has been studied. Furthermore the tumor micro environment in males with breast cancer has been explored

Strategies for clinical and public health management of sexually transmitted infections

This thesis reports on four different research topics at a sexually transmitted infections (STI) clinic: 1) evaluation of diagnostic tests, 2) clinical management, 3) public health surveillance, and 4) public health interventions. Three commercially available type-discriminating herpes simplex virus (HSV) antibody tests were evaluated in sera from patients with a recurrent genital HSV-1 or a recurrent genital HSV-2 episode. Also, the use of Gram-stained urethral smears to test for urogenital chlamydia was assessed. The prevalence, spontaneous clearance, and genotypes of pharyngeal C. trachomatis among STI clinic patients were examined. To find potential evidence for the possibility of LGV transmission from the urethra to the rectum, the positivity rate for urogenital LGV was established in a selection of men who have sex with men (MSM). Another study assessed the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) prevalence in MSM at the Amsterdam STI clinic. STI testing outcomes among three different populations at the Amsterdam STI clinic are evaluated. First the yield of hepatitis C screening in HIV-positive MSM and MSM opting-out of HIV testing is discussed. Next, the outcomes of STI screening in MSM requesting post-exposure prophylaxis (PEP) for HIV and finally, in victims of a sexual assault are evaluated. Lastly, two new interventions – chlamydia testing at home for young, low-risk heterosexual persons and an online partner notification website - are evaluated. Evaluations as described in this thesis are invaluable for STI clinics to make the right evidence-based decisions