Unlocking legal validity. Some remarks on the artificial ontology of law

Following Kelsen’s influential theory of law, the concept of validity has been used in the literature to refer to different properties of law (such as existence, membership, bindingness, and more) and so it is inherently ambiguous. More importantly, Kelsen’s equivalence between the existence and the validity of law prevents us from accounting satisfactorily for relevant aspects of our current legal practices, such as the phenomenon of ‘unlawful law’. This chapter addresses this ambiguity to argue that the most important function of the concept of validity is constituting the complex ontological paradigm of modern law as an institutional-normative practice. In this sense validity is an artificial ontological status that supervenes on that of existence of legal norms, thus allowing law to regulate its own creation and creating the logical space for the occurrence of ‘unlawful law’. This function, I argue in the last part, is crucial to understanding the relationship between the ontological and epistemic dimensions of the objectivity of law. For given the necessary practice-independence of legal norms, it is the epistemic accessibility of their creation that enables the law to fulfill its general action-guiding (and thus coordinating) function

THE CONCEPT OF LAW AND EFFICACY

Jedno od značenja izraza ‘učinkovitost’ odnosi se na činjenicu da se adresati pravnih normi stvarno ponašaju onako kako to od njih zahtijevaju pravne norme. To se značenje izraza obično koristi u filozofskopravnim raspravama glede toga je li učinkovitost bitan element pojma prava. Prema pravnom pozitivizmu, učinkovitost je u nekim slučajevima i na određene načine uvjet važenja (vrijeđenja) pravnih normi i pravnih sustava. S druge strane, pravni je realizam sklon potpunom poistovjećivanju pravnog važenja s učinkovitosti ili njegovu svođenju na učinkovitost. Prema tome, u oba je filozofskopravna pravca učinkovitost u pravilu uključena u oblikovanje njihovih pojmova prava. Međutim, dok pravnopozitivističko shvaćanje ne utječe na najuobičajenije značenje važenja pravne norme (pripadanje pravne norme pravnom sustavu), a utvrđivanjem učinkovitosti kao kriterija postojanja pravnog sustava ne dodaje mnogo objašnjenju pojma prava, pravnorealističko se shvaćanje suočava s ozbiljnim prigovorima glede svoje objašnjavalačke prikladnosti.One of the senses of the term ‘efficacy’ refers to the fact that norm-addresses actually behave as is required of them by legal norms. This sense of the term is one which is generally used within the jurisprudential discussions about whether efficacy is the essential element of the concept of law. According to legal positivism, efficacy is in some cases and in certain ways the condition of legal validity of both legal norms and legal systems. On the other hand, legal realism tends to entirely identify legal validity or reduce it to efficacy. Thus, in both jurisprudential approaches, efficacy tends to play a role in shaping their respective concepts of law. However, while the legal positivistic view does not affect the most standard sense of legal validity of the legal norm (i.e. the legal norms’ membership in the legal system), and does not add much to the explanation of the concept of law by identifying efficacy as the criterion of legal systems’ existence, the legal realistic view is faced with some serious objections regarding its explanatory adequacy

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools

BACKGROUND: We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. METHODS: Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. RESULTS: We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 ± 76.1 mm(3 )in SHRs and 16.9 ± 22.7 mm(3 )in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. CONCLUSIONS: We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and increase NPC proliferation profoundly. NPC proliferation was not aggravated by the presence of activated microglia. Intraluminal tMCAo in SHRs gave a more reliable infarct with neocortical involvement, but affected territories supplied by the anterior cerebral, anterior choroidal and hypothalamic arteries

Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer

In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg m−2 with cisplatin 60 mg m−2. In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg m−2 administered over 3 h followed by a 3-h infusion of cisplatin 60 mg m−2. Patients were retreated every 2 weeks unless granulocytes were <0.75×109 or platelets <75×109. Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32–78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2–29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20–29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin- and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting