The detection of hypointensities in PGGM appears to be a very promising surrogate MRI biomarker for ALS due to its simplicity, high sensitivity and specificity, suitability for longitudinal studies, and relationship with the pathogenesis of the disease.

No abstract

ALS is characterized by oxidative damage in the brain and cerebrospinal fluid, which is exerted by pro-oxidative activity of iron. Such activity of iron can be drastically increased in the presence of inappropriate iron ligands that catalyze redox cycling of iron, thereby promoting hydroxyl radical generation. The aim of our study was to determine the relative level of inappropriate iron ligands in the cerebrospinal fluid of ALS patients. To determine the levels of inappropriate iron ligands and redox activity of iron in cerebrospinal fluid (10 samples from ALS patients and 10 controls), we applied electron paramagnetic resonance spectroscopy. We have shown that cerebrospinal fluid of ALS patients comprises two-fold increased level of inappropriate iron ligands, proportionally increasing iron redox activity and hydroxyl radical production compared to controls. In conclusion, our results strongly support the pro-oxidative/detrimental role of inappropriately chelated iron in ALS pathophysiology. The identification of biomolecules that form such iron complexes and their therapeutic targeting may represent the future of ALS treatment.

In this paper we devise some technical tools for dealing with problems connected with the philosophical view usually called mathematical instrumentalism. These tools are interesting in their own right, independently of their philosophical consequences. For example, we show that even though the fragment of Peano's Arithmetic known as IΣ 1 is a conservative extension of the equational theory of Primitive Recursive Arithmetic (P RA), IΣ 1 has a super-exponential speed-up over P RA. On the other hand, theories studied in the Program of Reverse Mathematics that formalize powerful mathematical principles have only polynomial speed-up over IΣ 1 .

No abstract