Boyle, Spinoza and Glauber: On the Philosophical Redintegration of Saltpeter A Reply to Antonio Clericuzio

Traditionally, the so-called ‘redintegration experiment’ is at the center of the comments on the supposed Boyle/Spinoza correspondence. A. Clericuzio argued (refuting the interpretation by R.A. & M.B. Hall) in his influential publications that, in De nitro, Boyle accounted for the ‘redintegration’ of saltpeter on the grounds of the chemical properties of corpuscles and did not make any attempt to deduce them from the mechanical principles. By contrast, this paper claims that with his De nitro Boyle wanted to illustrate and promote precisely his new Corpuscular or Mechanical Philosophy, and that he did significant attempts to explain the phenomena in terms of mechanical qualities. Boyle had borrowed the ‘redintegration experiment’ from R. Glauber and used it as a tool to prove that his philosophy was the right alternative for the Peripatetic and Paracelsian theory of qualities of bodies. Consequently, Clericuzio’s characterization of the Boyle/Spinoza controversy as a discussion between a strict mechanical philosopher and a chemist is problematic and should be revised

Galileo Galilei, Holland and the pendulum clock

The pendulum clock was one of the most important metaphors for early modern philosophers. Christiaan Huygens (1629-1695) discovered his pendulum clock in 1656 based on the principle of isochronism discovered by Galileo (1564-1642). This paper aims at exploring the broad historical context of this invention, showing the role of some key figures such as Andreas Colvius (1594-1671), Elia Diodati (1576-1661), Hugo Grotius (1583-1645) and Constantijn Huygens, the father of Christiaan Huygens. Secondly, it suggests - based on this context - that it is hard to believe that Huygens did not know about Galileo’s idea to construct a pendulum regulated clock. Finally, this article illustrates how the Dutch philosopher Spinoza (1632-1677) might have been inspired by Huygens’ discovery of the synchronization of the pendulum clocks in his views on the agreement between bodies in the universe.The pendulum clock was one of the most important metaphors for early modern philosophers. Christiaan Huygens (1629-1695) discovered his pendulum clock in 1656 based on the principle of isochronism discovered by Galileo (1564-1642). This paper aims at exploring the broad historical context of this invention, showing the role of some key figures such as Andreas Colvius (1594-1671), Elia Diodati (1576-1661), Hugo Grotius (1583-1645) and Constantijn Huygens, the father of Christiaan Huygens. Secondly, it suggests - based on this context - that it is hard to believe that Huygens did not know about Galileo’s idea to construct a pendulum regulated clock. Finally, this article illustrates how the Dutch philosopher Spinoza (1632-1677) might have been inspired by Huygens’ discovery of the synchronization of the pendulum clocks in his views on the agreement between bodies in the universe.---Galileo Galilei, Holanda e o relógio de pênduloO relógio de pêndulo foi uma das metáforas mais importantes para os filósofos modernos. Christiaan Huygens (1629-1695) inventou o relógio de pêndulo em 1656 baseado no princípio do isocronismo descoberto por Galileo (1564-1642). Este artigo busca explorar o amplo contexto histórico dessa invenção, demonstrando o papel de algumas figuras-chave como Andreas Colvius (1594-1671), Elia Diodati (1576-1661), Hugo Grotius (1583-1645) e Constantijn Huygens, o pai de Christiaan Huygens. Em segundo lugar, sugere-se - baseado nesse contexto - que é difícil acreditar que Huygens não sabia da ideia de Galileo de construir um relógio regulado por um pêndulo. Por fim, este artigo ilustra como o filósofo holandês Espinosa (1632-1677) pode ter se inspirado nessa invenção de Huygens da sincronização do relógio de pêndulo em suas visões sobre o acordo entre os corpos no universo.---Original em inglês

Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>Data from a randomized multinational phase 3 trial of 320 adults with acute myeloid leukemia (AML) demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) but lacked power to detect an overall survival (OS) difference.</p> <p>Purpose</p> <p>To assess the consistency of treatment benefit across patient subsets and the robustness of data with respect to trial centers and endpoints.</p> <p>Methods</p> <p>Forest plots were constructed with hazard ratios (HRs) of HDC/IL-2 treatment effects versus no treatment (control) for prospectively defined patient subsets. Inconsistency coefficients (I²) and interaction tests (X²) were used to detect any differences in benefit among subsets. Robustness of results to the elimination of individual study centers was performed using "leave-one-center-out" analyses. Associations between treatment effects on the endpoints were evaluated using weighted linear regression between HRs for LFS and OS estimated within countries.</p> <p>Results</p> <p>The benefit of HDC/IL-2 over controls was statistically consistent across all subsets defined by baseline prognostic variables. I²and <it>P</it>-values of X²ranged from 0.00 to 0.51 and 0.14 to 0.91, respectively. Treatment effects were statistically significant in 14 of 28 subsets analyzed. The "leave-one-center-out" analysis confirmed that no single center dominated (<it>P</it>-values ranged from 0.004 to 0.020 [mean 0.009]). The HRs representing the HDC/IL-2 effects on LFS and OS were strongly correlated at the country level (R²= 0.84).</p> <p>Limitations</p> <p>Small sample sizes in some of the subsets analyzed.</p> <p>Conclusions</p> <p>These analyses confirm the consistency and robustness of the HDC/IL-2 effect as compared with no treatment. LFS may be an acceptable surrogate for OS in future AML trials. Analyses of consistency and robustness may aid interpretation of data from multicenter trials, especially in populations with rare diseases, when the size of randomized clinical trials is limited.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00003991">NCT00003991</a></p

Galileo Galilei, Holland and the pendulum clock

The pendulum clock was one of the most important metaphors for early modern philosophers. Christiaan Huygens (1629-1695) discovered his pendulum clock in 1656 based on the principle of isochronism discovered by Galileo (1564-1642). This paper aims at exploring the broad historical context of this invention, showing the role of some key figures such as Andreas Colvius (1594-1671), Elia Diodati (1576-1661), Hugo Grotius (1583-1645) and Constantijn Huygens, the father of Christiaan Huygens. Secondly, it suggests - based on this context - that it is hard to believe that Huygens did not know about Galileo’s idea to construct a pendulum regulated clock. Finally, this article illustrates how the Dutch philosopher Spinoza (1632-1677) might have been inspired by Huygens’ discovery of the synchronization of the pendulum clocks in his views on the agreement between bodies in the universe

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations

Changes in oxidative stress in response to different levels of energy restriction in obese ponies

The present study evaluated the effect of different levels of energy restriction on metabolic parameters in obese ponies. Relative weight changes, markers of lipid metabolism, and oxidant/antioxidant balance were monitored. Eighteen obese (body condition score≥7/9) Shetland ponies were studied over a 23.5 week trial, divided into 3 periods. First a 4 week adaptation period in which each animal was fed 100% of their maintenance energy requirements needed to maintain stable obese body weight (MERob). Then a 16.5 weeks weight loss period in which ponies were assigned to receive either 100% (control group, CONTROL), 80% (slow weight loss group, SLOW) or 60% (rapid weight loss group, RAPID) of their MERob. During the 3 week end phase period all animals were again fed 100% of their MERob. Relative weight loss was higher in RAPID (P<0.001) compared to SLOW. No linear relationship was found as a doubling in caloric restriction was accompanied with a tripling in weight loss. Relative weight gain afterwards in the end phase period was higher in RAPID (P<0.001) compared to SLOW and CONTROL. During the weight loss period, triacylglycerol and non-esterified fatty acids levels were highest in RAPID, as were α-tocopherol and ferric reducing ability of plasma. After 8 weeks of weight loss, advanced oxidation protein products were higher in RAPID compared to SLOW and CONTROL (P<0.001). In conclusion, the level of energy restriction influences the extent of changes in oxidant/antioxidant balance. Practically, more severe energy restriction regimens may be associated with a greater regain of weight post restriction

Surrogate markers and survival in women receiving first-line combination anthracycline chemotherapy for advanced breast cancer

Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC) . From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R2=34%), complete tumour response (P=0.02, R2=12%), progressive disease (P<0.001, R2=38%) and time to progression (P<0.0001, R2=56%); R2 is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good

A literature review of the predictive validity of European dental school selection methods

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Non peer reviewedPostprin