Stoics against stoics in Cudworth's "A Treatise of Freewill"

In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

Low Lipoprotein(a) Concentration Is Associated with Cancer and All-Cause Deaths: A Population-Based Cohort Study (The JMS Cohort Study)

Background: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. Methods The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a)≥80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined. Results: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15–1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00–2.13). Conclusions: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results

Lipoprotein(a) in the nephrotic syndrome: molecular analysis of lipoprotein(a) and apolipoprotein(a) fragments in plasma and urine.

Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, the absolute (24.7 +/- 20.4 versus 2.16 +/- 2.99 microg/ml, P &lt; 0.0001) as well as the relative amounts of apo(a) fragments (4.6 +/-3.4% versus 2.1 +/- 3.3% of total Lp(a), P &lt; 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 +/- 622 versus 27.7 +/- 44 ng/ml per mg creatinine, P &lt; 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 +/- 0.67% and 0.62 +/- 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine