"Antiscepticism and Easy Justification" - Ch 5 of Seemings and Epistemic Justification

In this chapter I investigate epistemological consequences of the fact that seeming-based justification is elusive, in the sense that the subject can lose this justification simply by reflecting on her seemings. I argue that since seeming-based justification is elusive, the antisceptical bite of phenomenal conservatism is importantly limited. I also contend that since seeming-based justification has this feature, phenomenal conservatism isn’t actually afflicted by easy justification problems

"Phenomenal Conservatism" - Ch 2 of Seemings and Epistemic Justification

In this chapter I introduce and analyse the tenets of phenomenal conservatism, and discuss the problem of the nature of appearances. After that, I review the asserted epistemic merits phenomenal conservatism and the principal arguments adduced in support of it. Finally, I survey objections to phenomenal conservatism and responses by its advocates. Some of these objections will be scrutinised and appraised in the next chapters

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib. Keywords: GSD Ib; Glycogen storage disease type Ib; Neutropenia; SGLT2 inhibitors; SLC37A

Immigration Enforcement and Fairness to Would-Be Immigrants

This chapter argues that governments have a duty to take reasonably effective and humane steps to minimize the occurrence of unauthorized migration and stay. While the effects of unauthorized migration on a country’s citizens and institutions have been vigorously debated, the literature has largely ignored duties of fairness to would-be immigrants. It is argued here that failing to take reasonable steps to prevent unauthorized migration and stay is deeply unfair to would-be immigrants who are not in a position to bypass visa regulations. Importantly, the argument here is orthogonal to the debate as to how much and what kinds of immigration ought to be allowed

Severe depletion of mitochondrial DNA in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromus- cular disorder in childhood leading to a dramatic loss of muscle strength. Functional investigations with high-reso- lution polarography and enzyme measurements of the res- piratory chain revealed lowered activities in muscle tissue of SMA patients. To gain a better understanding of this low energy supply we analyzed the amount of mitochon- drial DNA (mtDNA) in skeletal muscle of 20 unrelated children with genetically proven SMA and 31 controls. Quantitative Southern blot analysis revealed a severe and homogeneous decrease in the content of muscle mtDNA in relation to nuclear DNA in SMA patients (90.3±7.8%), whereas by immunofluorescence no decrease in the num- ber of mitochondria was detected. In addition, a two- to threefold reduction of the nuclear-encoded complex II (succinate dehydrogenase) activity was detected in SMA muscle tissue. Western blot analysis showed a significant reduction of both mitochondrial- and nuclear-encoded cy- tochrome c oxidase subunits. Our results indicate that mtDNA depletion in SMA is a consequence of severe at- rophy, and has to be differentiated by measurement of complex II from an isolated reduction of mtDNA as found in patients with mitochondriocytopathies and the so- called mtDNA depletion syndrome

"Cognitive Penetrability" - Ch 3 of Seemings and Epistemic Justification

In this chapter I introduce the thesis that perceptual appearances are cognitively penetrable and analyse cases made against phenomenal conservatism hinging on this thesis. In particular, I focus on objections coming from the externalist reliabilist camp and the internalist inferentialist camp. I conclude that cognitive penetrability doesn’t yield lethal or substantive difficulties for phenomenal conservatism

Rubber friction: role of the flash temperature

When a rubber block is sliding on a hard rough substrate, the substrate asperities will exert time-dependent deformations of the rubber surface resulting in viscoelastic energy dissipation in the rubber, which gives a contribution to the sliding friction. Most surfaces of solids have roughness on many different length scales, and when calculating the friction force it is necessary to include the viscoelastic deformations on all length scales. The energy dissipation will result in local heating of the rubber. Since the viscoelastic properties of rubber-like materials are extremely strongly temperature dependent, it is necessary to include the local temperature increase in the analysis. At very low sliding velocity the temperature increase is negligible because of heat diffusion, but already for velocities of order 0.01 m/s the local heating may be very important. Here I study the influence of the local heating on the rubber friction, and I show that in a typical case the temperature increase results in a decrease in rubber friction with increasing sliding velocity for v > 0.01 m/s. This may result in stick-slip instabilities, and is of crucial importance in many practical applications, e.g., for the tire-road friction, and in particular for ABS-breaking systems.Comment: 22 pages, 27 figure

Realism, Objectivity, and Evaluation

I discuss Benacerraf's epistemological challenge for realism about areas like mathematics, metalogic, and modality, and describe the pluralist response to it. I explain why normative pluralism is peculiarly unsatisfactory, and use this explanation to formulate a radicalization of Moore's Open Question Argument. According to the argument, the facts -- even the normative facts -- fail to settle the practical questions at the center of our normative lives. One lesson is that the concepts of realism and objectivity, which are widely identified, are actually in tension