Persons, Agents, and the End-of-life Decisions

Extensive discussions about the nature and value of personhood, of metaphysical and normative aspects of becoming a person and ceasing to be one, having been conducted at the very center of the debates on abortion, therapeutic human cloning, embryo experimentation, and so on, for decades have proven notoriously difficult and their insights disappointingly inconclusive. In the paper I would like to turn our attention to the other end of the life span and explore the moral implications of acknowledging to, or witholding from, someone the status of a person, i.e. a rational being, for the choice between prolonging her life and facilitating her death. The philosophical challenge facing the opponent of euthanasia can then be put as follows: suppose the patient's decision to have her life terminated is both voluntary and prudent; further suppose that neither her decision nor the carrying out of it by a health professional violates anyone's rights or fails to discharge anyone's duties. What else could possibly make the doctor's compliance with the patient's request wrong and what other moral objections could possibly be raised against the proposal to provide a legal protection for such an option for the terminally-ill patients

The False Promise of Thought Experimentation in Moral and Political Philosophy

Prof. Miščević has long been an ardent defender of the use of thought experiments in philosophy, foremost metaphysics, epistemology and philosophy of mind. Recently he has, in his typically sophisticated manner, extended his general account of philosophical thought-experimenting to the domain of normative politics. Not only can the history of political philosophy be better understood and appreciated, according to Miščević, when seen as a more or less continuous, yet covert, practice of thought-experimenting, the very progress of the discipline may crucially depend on finding the right balance between the constraints of (biological, psychological, economic, political, and so on) reality and political-moral ideals when we set to design our basic political notions and institutions. I have much less confidence in this project than prof. Miščević does. As a subspecies of moral TE, political TE share all their problems plus exhibit some of their own. In the paper, I present and discuss two types of evidence that threaten to undermine political philosophers’ trust in thought-experiments and the ethical/political intuitions elicited by them: (i) the dismal past record of thought-experimentation in moral and political philosophy; and (ii) the variety, prevalence, and stubbornness, of bias in ordinary social/political judgment

Hepatocyte growth factor, a key tumor-promoting factor in the tumor microenvironment

The tumor microenvironment plays a key role in tumor development and progression. Stromal cells secrete growth factors, cytokines and extracellular matrix proteins which promote growth, survival and metastatic spread of cancer cells. Fibroblasts are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor (HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major component of their secretome. Indeed, cancer-associated fibroblasts have been shown to promote growth, survival and migration of cancer cells in an HGF-dependent manner. Fibroblasts also confer resistance to anti-cancer therapy through HGF-induced epithelial mesenchymal transition (EMT) and activation of pro-survival signaling pathways such as ERK and AKT in tumor cells. Constitutive HGF/MET signaling in cancer cells is associated with increased tumor aggressiveness and predicts poor outcome in cancer patients. Due to its role in tumor progression and therapeutic resistance, both HGF and MET have emerged as valid therapeutic targets. Several inhibitors of MET and HGF are currently being tested in clinical trials. Preclinical data provide a strong indication that inhibitors of HGF/MET signaling overcome both primary and acquired resistance to EGFR, HER2, and BRAF targeting agents. These findings support the notion that co-targeting of cancer cells and stromal cells is required to prevent therapeutic resistance and to increase the overall survival rate of cancer patients. HGF dependence has emerged as a hallmark of therapeutic resistance, suggesting that inhibitors of biological activity of HGF should be included into therapeutic regimens of cancer patients

Early verb development in one austrian child

The purpose of this paper is to trace the early development of verbs (first 50 verb lemmas) in one Austrian child. The paper focusses on verb morphology, and especially on the emergence of first verb paradigms

Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Euthanasia Laws, Slippery Slopes, and (Un)reasonable Precaution

The article examines the so-called slippery slope argument (SSA) against the legalization of active voluntary euthanasia (AVE). According to the SSA, by legalizing AVE, the least morally controversial type of euthanasia, we will take the first step onto a slippery slope and inevitably end up in the moral abyss of widespread abuse and violations of the rights of the weakest and most vulnerable patients. In the first part of the paper, empirical evidence to the contrary is presented and analyzed: None of the forecasted regrettable trends can be elicited from the body of existing statistical data. Accordingly, we have no good reason to believe either that we already are, or are sooner or later going to be, sliding into a moral abyss. A related question is then considered: Would it not be wiser and safer to stick to the status quo and preserve the existing legal ban on AVE even if the risk of its abuse is uncertain and may well turn out to be relatively low? It is argued that such an appeal to precautionary reasoning fails to justify an outright legal ban on AVE for at least two reasons: (i) it grossly underestimates the hidden moral costs of current legal arrangements (competent terminal patients suffer both disrespect for their autonomous will and deprivation of the good of a timely death) and (ii) the ban is both too inefficient and disproportionate to qualify as a reasonable measure of precaution

Moral Thought-Experiments, Intuitions, and Heuristics

Philosophical thought-experimentation has a long and influential history. In recent years, however, both the traditionally secure place of the method of thought experimentation in philosophy and its presumed epistemic credentials have been increasingly and repeatedly questioned. In the paper, I join the choir of the discontents. I present and discuss two types of evidence that in my opinion undermine our close-to-blind trust in moral thought experiments and the intuitions that these elicit: the disappointing record of thought-experimentation in contemporary moral philosophy, and the more general considerations explaining why this failure is not accidental. The diagnosis is not optimistic. The past record of moral TEs is far from impressive. Most, if not all, moral TEs fail to corroborate their target moral hypotheses. Moral intuitions appear to be produced by moral heuristics which we have every reason to suspect will systematically misfi re in typical moral TEs. Rather than keep relying on moral TEs, we should therefore begin to explore other, more sound alternatives to thought-experimentation in moral philosophy

Terorizmi in (drugi) ekstremizmi

The article pursues two goals: to provide a working definition of terrorism and to critically evaluate the argumentative strategies leading to its near-universal moral condemnation. The author advocates for a definition of terrorism tailored to the needs of moral evaluation: the indiscriminate use of violence—or the serious threat thereof— with the aim or purpose of coercing (authorities) into implementing more or less radical political or social changes. Regarding the second, the author acknowledges that terrorists, through deliberate, but indiscriminate physical and psychological violence, assume a heavy moral burden. However, the argument is made that terrorism is not significantly different in this respect from other forms of politically motivated violence that are generally tolerated or even celebrated and admired, such as armed uprisings, and wars. Whether terrorism ultimately collapses under this moral burden will depend on the concrete justification, interpretation, and application of the principle of civilian immunity—a task far more challenging upon reflection than its commonly assumed. Finally, there are no compelling reasons to equate terrorism with extremism, especially when one considers how much more lenient we are toward other forms of politically motivated violence, which are, at best, morally equivalent to terrorism and, at worst, inferior.V pričujočem članku zasleduje avtor dva cilja – najprej podati delovno definicijo terorizma, nato pa kritično ovrednotiti argumentacijske strategije, ki vodijo do njegove skoraj soglasne moralne obsodbe. V zvezi s prvim zagovarja potrebam moralnega ovrednotenja prikrojeno definicijo terorizma kot ne-razlikovalne uporabe nasilja – ali resno mišljene grožnje z njim – z namenom/ciljem (od oblasti) izsiliti bolj ali manj korenite politične oz. družbene spremembe. V zvezi z drugim priznava, da si teroristi z načrtnim fizičnim in psihičnim nasiljem nad civilisti naprtijo težko moralno breme, a dokazuje, da terorizem v tem ni pomembno drugačen od drugih, praviloma toleriranih in neredko celo slavljenih in občudovanih vrst politično motiviranega nasilja, od oboroženih uporov in revolucij do državljanskih in meddržavnih vojn. Ali se bo terorizem pod navedenim moralnim bremenom nazadnje zlomil ali ne, bo v prvi vrsti odvisno od konkretne utemeljitve, tolmačenja in uporabe načela imunosti civilistov – ta naloga pa se po premisleku izkaže za precej trši oreh, kot dajeta slutiti njegova samoumevnost in vsesplošna popularnost. In končno, za enačenje terorizma in ekstremizma ni prepričljivih razlogov, sploh če pomislimo, koliko strpnejši smo do drugih pojavnih oblik politično motiviranega nasilja, ki so terorizmu v najboljšem primeru moralno enakovredne ali pa še to n