Getting Acquainted with Kant

My question here concerns whether Kant claims that experience has nonconceptual content, or whether, on his view, experience is essentially conceptual. However there is a sense in which this debate concerning the content of intuition is ill-conceived. Part of this has to do with the terms in which the debate is set, and part to do with confusion over the connection between Kant’s own views and contemporary concerns in epistemology and the philosophy of mind. However, I think much of the substance of the debate concerning Kant’s views on the content of experience can be salvaged by reframing it in terms of a debate about the dependence relations, if any, that exist between different cognitive capacities. Below, in Section 2, I clarify the notion of ‘content’ I take to be at stake in the interpretive debate. Section 3 presents reasons for thinking that intuition cannot have content in the relevant sense. I then argue, in Section 4, that the debate be reframed in terms of dependence. We should distinguish between Intellectualism, according to which all objective representation (understood in a particular way) depends on acts of synthesis by the intellect, and Sensibilism, according to which at least some forms of objective representation are independent of any such acts (or the capacity for such acts). Finally, in Section 5, I further elucidate the cognitive role of intuition. I articulate a challenge which Kant understands alethic modal considerations to present for achieving cognition, and argue that a version of Sensibilism that construes intuition as a form of acquaintance is better positioned to answer this challenge than Intellectualism

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities

The risk of adverse cardiovascular outcomes after bariatric surgery in patients with morbid obesity with and without obstructive sleep apnea

Background: Weight loss after bariatric surgery in obese patients reduces adverse cardiovascular (CV) outcomes; however, it is not known if similar benefits are maintained in patients with and without obstructive sleep apnea (OSA). We investigated whether weight loss after laparoscopic adjustable gastric banding (LAGB) results in similar CV event rates in patients with and without OSA. Methods: Differences in LAGB-induced weight loss on CV outcomes (myocardial infarction, heart failure, stroke, atrial fibrillation [AF] and pulmonary embolism) in those with OSA and matched non-OSA patients were determined by Kaplan-Meier and Cox regression analysis and predictors of CV events identified. Results:Out of 828 obese patients [body mass index (BMI) ≥35 kg/m2] who underwent LAGB and were followed for 11 years, OSA was present in 217 (26%).The mean age was 44±11 years, mean BMI 49±8 kg/m2 and median follow-up 63.6 months; the mean reduction in BMI was 10 kg/m2 at 3 years. Patients with no history of OSA had minimal CV events compared to those with OSA (Fig A and B, at 5 years 1% vs 22%, p Conclusions: Patients with OSA, despite weight loss after LABG, continued to have higher CV events, particularly heart failure and AF. Further investigation is warranted into whether compliance with OSA treatment helps reduce CV events

Gender differences in risk of stroke in patients with restless legs syndrome

Background Patients with Restless Legs Syndrome (RLS) have been recently reported to have a higher risk of stroke when compared to non-RLS patients, but the difference appears to be related to the duration of RLS. We hypothesize that diabetes mellitus, a condition that accelerates cardiovascular diseases, may enhance the risk of stroke more in RLS than in non-RLS patients. Methods and Results Patients diagnosed with RLS based on the International Restless Legs Syndrome Study Group criteria from a community-based sleep study center were compared to a 1:2 propensity matched non-RLS group. The association of diabetes and stroke in RLS and non-RLS patients in men and women were performed using Chi-Square and Cochran-Mantel-Haenszel Tests. Results Stroke was diagnosed in 29 out of 385 (7.5%) patients with RLS (mean age 55.1±0.7 years, 45% female) which was significantly higher than 32 out of 770 (4.2%; p=0.02) patients without RLS (mean age 54±0.5 years, 46% females). The presence of diabetes in the RLS group was associated with a 3 fold increased risk of stroke (OR 2.96, 95% Confidence Interval 1.05-8.37, p=0.03) compared to a 1.1 fold increased risk in non-RLS patients (OR: 1.08, 95% CI 0.44-2.65; p=0.87). This was significantly higher in female diabetics with RLS (18.2%) than in male diabetics (7.0%, p=0.03) or nondiabetics (5.7% in females vs 3.9% in males, p=0.52). Predictors of stroke in patients with RLS were the presence of hypertension, diabetes and female sex. Hypertension, diabetes and atrial fibrillation were predictors of stroke in non-RLS patients. Conclusions Gender differences exist in the risk of stroke in RLS patients with a 3.0 fold higher risk of stroke in diabetic women compared to diabetic men. In non-RLS patients, no significant difference in risk of stroke was found between women and men. Mechanisms underlying increased risk of stroke in RLS patients need to be defined and whether better diabetes control help reduce the stroke risk in RLS patients needs to be further investigated

Impact of obstructive sleep apnea severity on cardiac events in patients with normal or prolonged ventricular repolarization

BACKGROUND: Prolonged cardiac repolarization is associated with increased risk of ventricular arrhythmias which are aggravated by several triggering factors including excess catecholamine state and electrolyte abnormalities. We studied the impact of severity of obstructive sleep apnea (OSA) on ventricular tachyarrhythmias and mortality in patients with normal or prolonged ventricular repolarization as this is not well defined. METHODS: 338 patients [59% male, mean age: 61 ± 13] undergoing polysomnography between January 2012 to June 2015 who also had a 12-lead ECG were divided into 4 groups: Group 1-no evidence of OSA, Group 2-mild, Group 3-moderate, Group 4-severe, based on apnea-hypopnea index (AHI) none\u3c5, mild 5-14, moderate 15-29, severe \u3e29 respectively. The differences in prevalence of non-sustained ventricular tachycardia between the 4 groups and incidence of ventricular fibrillation (VF) and overall mortality were determined using Cochran-Armitage Trend and Chi-Square. In addition, differences in VT and VF and overall mortality were determined between the 4 groups and compared to those with normal or prolonged repolarization (defined as JTc interval [JTc=QTc -QRS] \u3e380ms for female and \u3e360ms for male). RESULTS: Out of 338 patients, [51% with preexisting heart failure] the prevalence of VT increased with OSA severity from 44% in Group 1 to 46%, 50%, 67% in Group 2 to 4 [p=0.004] respectively. In patients with normal repolarization, prevalence of VT increased with OSA severity from 33% in Group 1 to 50%, 60% and 84% in Group 2 to 4 [p=0.001]. However, in patients with prolonged repolarization, there was no additional impact of OSA severity on VT in Group 1 to 4: 50%, 45%, 45%, 60% [p=0.094]. The risk of VF or death increased with worsening OSA severity from Groups 1 -4: 2.7%, 5.4%, 5.8%, 9.8%, however this was not significantly significant [p=0.53]. CONCLUSIONS: In patients with underlying cardiac disease, the prevalence of VT increases with OSA severity mainly in patients with normal repolarization but have minimum effect on patients with prolonged repolarization. There is a trend toward higher risk of VF or death with worsening sleep apnea that needs to be confirmed in a larger population

Myo-inositol, probiotics and micronutrient supplementation from preconception for glycemia in pregnancy: NiPPeR international multi-center double-blind randomized controlled trial

Objective: Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited. Research design and methods: This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test). Results: Between 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] loge mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted β = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates. Conclusions: Supplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth

Myo-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial

ObjectiveBetter preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited.Research design and methodsThis double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test).ResultsBetween 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P e mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted β = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates.ConclusionsSupplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth

Role of maternal tryptophan metabolism in allergic diseases in the offspring

10.1111/cea.13953Clinical and Experimental AllergyCLEA