Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

_Background:_ We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. _Methods:_ Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age and interval. The benefits and harms were compared with those seen with 3 established screening guidelines. _Results:_ Women with a breast cancer family history who initiated biennial screening at age 40 years had a 36% increase in life-years gained and 20% more breast cancer deaths averted, but 21% more overdiagnoses and 63% more false positives. Screening tailored to PRS vs biennial screening from50 to 74 years had smaller positive effects on life-years gained and breast cancer deaths averted but also smaller increases in overdiagnoses and false positives. Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained and breast cancer deaths averted. _Conclusions:_ Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected

The Centrality of Mathematics in the History of Western Thought

This article explores the interplay of mathematics and philosophy in Western thought as well as applications to other fields

Emanació i creació del no-res en Hasday Cresques

L'emanació és una idea que deriva de Plotí, La creació del no-res prové de 2Ma 7,28. Ambdues tenen en comú la idea que la formació del món depèn d'una primera causa: de Déu; però difereixen en la manera d'explicar aquesta formació. La doctrina de l'emanació suposa que el món sortí de la substància de Déu, mentre que la doctrina de la creació del no-res admet que el món fou creat per Déu de l'absència absoluta de tota realitat. Cresques malda per demostrar que el concepte de no-res no significa que el no-res' sigui el substrat del qual emanà el món, ans que el món existí després' de la seva no existència o privació. La idea d'emanació, cal entendre-la en el sentit que la «matèria i la forma emanaren, juntes, després de llur privació». Cresques arriba a la conclusió que eren una sola i única concepció, malgrat que fossin expressades amb paraules diferents.Emanation and creation ex nihilo are two theories about the origin of the world that are usually set against each other. Emanation is a philosophical conception derived from Plotinus, despite the fact that Arab thinkers before Averroës including Maimonides would also attribute it to Aristotle. Creation out of nothing, on the other hand, is based on the Second Book of the Maccabees (7,28), even though Maimonides and most mediaeval thinkers would trace it back to the history of creation in Genesis. Both theories have in common the idea that the formation of the world depends on a first cause, namely on God; but they differ in the way in which they explain that formation by Gods causality. According to the emanation theory, the world came out of Gods substance, while the theory of creation out of nothing affirms that the world was created by God out of nothing, that is to say, from an absolute privation or absence of all reality. Crescas deals with these two theories in one of his reflections on the theory of creation put forward by Levi ben Gerson, in which Crescas strives to demonstrate that the idea of nothing does not mean that nothing is the substratum from which the world emanated, but rather that the world existed after its non-existence or privation. Also the idea of emanation should be understood in the sense that «matter and form emanated together after their privation». Considering that the two conceptions mean the same, Crescas came to the conclusion that they are one single conception despite their being expressed in different words. On that score, he points out that emanation can be by necessity or by will, and explains the difference that exists between the two conceptions in relation to the voluntary nature of creation and its temporal beginning. In the present article, the author confines himself to a discussion of the sources and parallels of three of the points dealt with by Crescas in that reflection, namely: (1) that the expression out o

Emanació i creació del no-res en Hasday Cresques

L'emanació és una idea que deriva de Plotí, La creació del no-res prové de 2Ma 7,28. Ambdues tenen en comú la idea que la formació del món depèn d'una primera causa: de Déu; però difereixen en la manera d'explicar aquesta formació. La doctrina de l'emanació suposa que el món sortí de la substància de Déu, mentre que la doctrina de la creació del no-res admet que el món fou creat per Déu de l'absència absoluta de tota realitat. Cresques malda per demostrar que el concepte de no-res no significa que el ‘no-res' sigui el substrat del qual emanà el món, ans que el món existí ‘després' de la seva no existència o privació. La idea d'emanació, cal entendre-la en el sentit que la «matèria i la forma emanaren, juntes, després de llur privació». Cresques arriba a la conclusió que eren una sola i única concepció, malgrat que fossin expressades amb paraules diferents.Emanation and creation ex nihilo are two theories about the origin of the world that are usually set against each other. Emanation is a philosophical conception derived from Plotinus, despite the fact that Arab thinkers before Averroës —including Maimonides— would also attribute it to Aristotle. Creation out of nothing, on the other hand, is based on the Second Book of the Maccabees (7,28), even though Maimonides and most mediaeval thinkers would trace it back to the history of creation in Genesis. Both theories have in common the idea that the formation of the world depends on a first cause, namely on God; but they differ in the way in which they explain that formation by God’s causality. According to the emanation theory, the world came out of God’s substance, while the theory of creation out of nothing affirms that the world was created by God out of nothing, that is to say, from an absolute privation or absence of all reality. Crescas deals with these two theories in one of his reflections on the theory of creation put forward by Levi ben Gerson, in which Crescas strives to demonstrate that the idea of nothing does not mean that ‘nothing’ is the substratum from which the world emanated, but rather that the world existed ‘after’ its non-existence or privation. Also the idea of emanation should be understood in the sense that «matter and form emanated together after their privation». Considering that the two conceptions mean the same, Crescas came to the conclusion that they are one single conception despite their being expressed in different words. On that score, he points out that emanation can be by necessity or by will, and explains the difference that exists between the two conceptions in relation to the voluntary nature of creation and its temporal beginning. In the present article, the author confines himself to a discussion of the sources and parallels of three of the points dealt with by Crescas in that reflection, namely: (1) that the expression ‘out o

Emanació i creació del no-res en Hasday Cresques

L'emanació és una idea que deriva de Plotí, La creació del no-res prové de 2Ma 7,28. Ambdues tenen en comú la idea que la formació del món depèn d'una primera causa: de Déu; però difereixen en la manera d'explicar aquesta formació. La doctrina de l'emanació suposa que el món sortí de la substància de Déu, mentre que la doctrina de la creació del no-res admet que el món fou creat per Déu de l'absència absoluta de tota realitat. Cresques malda per demostrar que el concepte de no-res no significa que el no-res' sigui el substrat del qual emanà el món, ans que el món existí després' de la seva no existència o privació. La idea d'emanació, cal entendre-la en el sentit que la «matèria i la forma emanaren, juntes, després de llur privació». Cresques arriba a la conclusió que eren una sola i única concepció, malgrat que fossin expressades amb paraules diferents.Emanation and creation ex nihilo are two theories about the origin of the world that are usually set against each other. Emanation is a philosophical conception derived from Plotinus, despite the fact that Arab thinkers before Averroës including Maimonides would also attribute it to Aristotle. Creation out of nothing, on the other hand, is based on the Second Book of the Maccabees (7,28), even though Maimonides and most mediaeval thinkers would trace it back to the history of creation in Genesis. Both theories have in common the idea that the formation of the world depends on a first cause, namely on God; but they differ in the way in which they explain that formation by Gods causality. According to the emanation theory, the world came out of Gods substance, while the theory of creation out of nothing affirms that the world was created by God out of nothing, that is to say, from an absolute privation or absence of all reality. Crescas deals with these two theories in one of his reflections on the theory of creation put forward by Levi ben Gerson, in which Crescas strives to demonstrate that the idea of nothing does not mean that nothing is the substratum from which the world emanated, but rather that the world existed after its non-existence or privation. Also the idea of emanation should be understood in the sense that «matter and form emanated together after their privation». Considering that the two conceptions mean the same, Crescas came to the conclusion that they are one single conception despite their being expressed in different words. On that score, he points out that emanation can be by necessity or by will, and explains the difference that exists between the two conceptions in relation to the voluntary nature of creation and its temporal beginning. In the present article, the author confines himself to a discussion of the sources and parallels of three of the points dealt with by Crescas in that reflection, namely: (1) that the expression out o

Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History.

BACKGROUND: We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. METHODS: Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age (30, 35, 40, 45, and 50 years) and interval (annual, hybrid, biennial, triennial). The benefits (breast cancer deaths averted, life-years gained) and harms (false-positive mammograms, overdiagnoses) were compared with those seen with 3 established screening guidelines. RESULTS: Women with a breast cancer family history who initiated biennial screening at age 40 years (vs 50 years) had a 36% (model range = 29%-40%) increase in life-years gained and 20% (model range = 16%-24%) more breast cancer deaths averted, but 21% (model range = 17%-23%) more overdiagnoses and 63% (model range = 62%-64%) more false positives. Screening tailored to PRS vs biennial screening from 50 to 74 years had smaller positive effects on life-years gained (20%) and breast cancer deaths averted (11%) but also smaller increases in overdiagnoses (10%) and false positives (26%). Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained (29%) and breast cancer deaths averted (18%). CONCLUSIONS: Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected