Alexandra : Echoes of His Sins

LV meridional wall stress was assessed using validated formula: The endocardial borders were traced in the end-systolic frame of the 2D images from the 3 apical views. Speckles were tracked frame by-frame throughout the LV wall during the cardiac cycle and basal, mid, and apical regions of interest were created. Segments that failed to track were manually adjusted by the operator. GLS was calculated as the mean strain of 18 segments.

This method has been validated and well described by Kusunose et al[ 28 ] and Su et al[ 29 ] as a reliable way to assess GLS in patients with AF. Record was made of those patients who had undergone renal transplantation and those who remained on renal dialysis. All-cause mortality was defined as death from any cause. Average length of follow up was 7. Deceased patients were identified from the medical records at Princess Alexandra Hospital, Brisbane, Australia and ANZDATA registry and were matched according to first name, last name, identification number and date of birth.

Individuals with incomplete data were contacted through general practitioners or telephone interview with their families and were excluded if data was missing 17 patients. One hundred and twelve deceased patients were identified. All other patients were considered to be alive at the end of the follow-up period.

Forty six cardiac deaths were identified. Univariate analysis was performed to assess relationships between baseline demographic, biochemical, echocardiographic parameters and the clinical outcomes of CV and all-cause mortality. Cox proportionate hazard models were used to determine significant predictors of all-cause and CV mortality. To further compare the predictive value of EF and GLS, nested cox models with separate addition of EF and GLS to a baseline model containing significant demographic and biochemical co-variates were constructed.

The independence and incremental value of each measure of LV function over baseline was assessed using likelihood-ratio tests. Interaction terms were examined for GLS and other significant predictors of mortality. P values less than 0. Competing-risks regression was performed to adjust for renal transplantation during follow-up as a competing risk in the survival analyses.

The clinical and echocardiographic characteristics of patients are presented in Table 1. The median duration on dialysis during follow-up was 1. This includes cardiac arrest There was no difference in mortality rates among patients with preserved or impaired EF. In contrast, EF was not predictive of all-cause or CV deaths. Following adjustment with multivariable analysis, worsening GLS remained a significant predictor of all-cause mortality HR 1. The predictive power of GLS and EF was also assessed in separate nested Cox models to obtain additional prognostic information on each measure of LV function.

Similarly, discriminatory analysis with c-statistics showed the addition of GLS to baseline models improved risk prediction of all-cause mortality [0. However, there was no association between GLS and overall mortality in this subgroup. Due to the limited number of patients and events, we did not proceed to evaluate the independent association of GLS and CV mortality with multiple regression models. Sensitivity analysis using a competing risk regression model was used to delineate the confounding effect of renal transplantation on the outcomes.

The predictive value of GLS for survival was superior to other established CV risk factors and without confounding effects of receiving renal transplant. Few studies have assessed the prognostic value of myocardial strain assessment in CKD. We previously reported the relationship between GLS with renal impairment and all-cause mortality and found that GLS was a sensitive discriminator over significant clinical risk factors in predicting all-cause mortality[ 19 ].

In a cohort of 88 stable hemodialysis patients with preserved EF and a mean follow-up of More recently, Kramann et al demonstrated the ability of strain parameters to identify uremic cardiomyopathy and predict CV mortality in dialysis patients[ 20 ]. The current study had a more inclusive cohort encompassing stable hemodialysis, peritoneal dialysis and pre-dialysis stage 4 and 5 CKD patients and involved a much longer duration of follow-up. Several observational and prospective studies in unselected populations with heart failure, myocardial infarction and cardiomyopathy[ 13 — 15 , 17 , 36 ] have identified prognostic value and superior risk stratification of GLS compared to EF [ 37 ].

In a recent study by Ersboll et al who assessed patients with acute myocardial infarction MI within 48 hours of admission, GLS outperformed EF and biochemical measurement of N-terminal pro-brain natriuretic peptide, in predicting in-hospital heart failure[ 36 ]. This intriguing finding warrants further evaluation as our observation was limited by a small number of participants in this subgroup. Furthermore, as HF is a common cause of CV death in patients with HF with preserved EF[ 38 , 39 ], the ability to risk stratify these patients and compare GLS with other parameters of LV function requires further investigation with larger studies.

Emerging evidence from general population studies has identified similar systolic abnormalities in patients with preserved EF. Similarly, patients with heart failure and preserved ejection fraction HFpEF were shown to have significantly lower GLS compared to a control population[ 40 ].

Although GLS and EF are highly correlated, they measure different aspects of the myocardial deformation. EF predominantly quantifies radial contraction and GLS represents the function of subendocardial longitudinal myocardial fibres that are more sensitive to reduced coronary perfusion and increased wall stress. GLS not only provides quantitative assessment of myocardial function but also reflects changes in the myocardial interstitium including extent of myocardial fibrosis[ 20 , 43 ].

CKD is a unique risk factor for cardiac remodelling; animal models have demonstrated that early subendocardial changes are significantly worse in CKD compared to non-CKD rats following similar cardiac insults[ 44 ]. CKD specific disturbances such as hyperuricemia, abnormal bone mineral metabolism, pressure and volume overload have been shown to drive these mechanistic changes[ 45 , 46 ]. Two studies have observed no difference in GLS measurements in relation to timing of hemodialysis [ 35 , 47 ]. However, similar to EF, GLS has been shown to be sensitive to loading conditions especially afterload[ 48 ].

It is important to note that systolic BP is a major determinant of GLS[ 32 ] and should be meticulously included at the time of measurement. Variation in GLS measurements due to loading conditions among dialysis patients should be further examined. This study has a number of strengths. However the results of this study warrant careful interpretation due to some limitations: This discrepancy could be due to our sample size; 3 previous studies have also shown that diastolic dysfunction occurs in early stages of CKD and can predict adverse outcome[ 49 , 50 ]; however in this study we did not have measures of diastolic function in majority of patients to directly compare prognostic relevance of systolic and diastolic function.

Additional studies are required to identify the prognostic utility of GLS in CKD patients with diastolic dysfunction and in patients with preserved EF; 5 even though we adjusted for a large number of patient characteristics, the possibility of residual confounding also cannot be excluded; 6 we used resting echocardiogram and were unable to identify inducible ischemia as one of the predictors of mortality; 7 inter-vendor variability can affect GLS measurements, thus the prognostic value of GLS shown here may be limited to the equipment used in this study.

In conclusion, the present study demonstrated that GLS is associated with all-cause and cardiovascular mortality among patients with advanced CKD. There are no additional funding sources for this study. National Center for Biotechnology Information , U. Published online May Isbel , 1 , 2 Carmel M. Hawley , 1 , 2 Elaine M. Haluska , 3 Thomas H. The former school seems to have disappeared as a structured institution by his lifetime. The latter came to prominence in the middle of the first century BCE, with Enesidemus criticizing New Academic philosophers, and especially those of his age, on the grounds that they had conceded far too much to Stoic dogma.

Philo seems to have paid little attention to New Academic sceptics, but was acquainted at least with some of their principal doctrines. By contrast, he is the first to have used the tropes, i. At the beginning of the twentieth century and for many years after, scholars paid great attention to the passage of the De ebrietate where Philo uses these tropes. Today, however, it is commonplace to say that the connection was a weak one, and that Philo had his own interests instead.

Of course he did, but Sextus Empircus himself, now considered the most reliable source, had his own interests as well as being a physician, and it is rash at least to neglect the Philonian testimony, closer to Enesidemus from both a geographical and chronological point of view. Philo uses Sceptic methods to demonstrate that even with the aid of education, the paideia of which he was so proud, human beings are unable to find the truth. Skepticism thus appears as the best means to awaken mankind to its oudeneia and to open the path toward transcendence.

There is at least one point of consensus among the scholars, i. Very useful comparisons have been made with Eudorus, a contemporary and compatriot, and with Plutarch. At the same time, Philo makes extensive use of Plato as well despite the difficulty of reconciling this doctrine with more classical Platonic themes. The presence of the Timaeus in the De opificio mundi is massive, as demonstrated by Runia On the contrary, for Middle Platonists who were readers and commentators of the Theaetetus , the goal was to depart from nature, a dwelling of sensations and injustice, in order to become as similar as possible to God.

Another major theme that Philo shares with other Middle Platonists is that of Ideas as divine thoughts, one of the features of Imperial Platonism. For him God is, through his logos , the only active cause. Despite many nuances, variations, and even contradictions, there is in Philo the same triple structure common to many Middle Platonic texts: However, it must be added that in Philo everything is both similar and different. His God is not the Demiurge; he does not define powers and Ideas with reference to mathematical principles, though arithmology is quite present in his commentaries; and his conception of matter, despite many allusions to the philosophical doctrine of the dyad the formless and unlimited base , has deep Biblical roots.

It may be useful at this point to address the question of Pythagorean influence on Philo. He explicitly mentions twice Pythagorean sources: Nevertheless, his allusions to Pythagorean themes are often vague and merit further analysis. As an example, Philo is often willing to use adjectives by which Pythagoreans characterized the dyad but reluctant to use the word itself.

Monad and dyad serve Philo as exegetical tools, not actual substitutes for the narrative of Creation in the Bible.

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It is as if the imperative not to coincide exactly with Greek philosophical doctrine was for Philo an obligation of identity. Evidently, Philo felt no sympathy towards Epicureanism, an exclusively materialistic doctrine which denied the existence of Providence and defined pleasure both as the first motivator of human actions and as the supreme good.

As if this was not enough, Epicureans also described gods as taking human form, which was for Philo an indisputable case of idolatry. Nevertheless, his attitude towards Epicureanism is at times more complex than one might expect. In the first instance, his condemnation of Epicureanism is clear. In the same sentence at Post. In De providentia as well we find strong elements of a refutation of Epicurean denial of Providence. In addition, atomism becomes an allegorical instrument in the splendid exegesis of Moses killing the Egyptian Fug. The Egyptian, who symbolizes pleasure, is buried in the sand, symbol of atoms.

Nothing in all this is truly unexpected. Moreover, despite many appearances, Philo does not consider pleasure an absolute evil. For him, it has a place in the divine program of Creation since it plays an essential role in procreation. The error lay with those who would transform a relative good into a perfect one. There are many arguments to defend this association, but it would be an error to affirm that he was merely an allegorist. In many passages he defines with precision what can be called his methodology of allegory. He distinguishes three cases by which a secret meaning may be ascertained: It must be added that he not only uses the word allegoria , but also uponoia , a Platonic term which by this time may have been somewhat archaic.

The two terms are not exactly synonymous for him. Nevertheless, according to Philo, it is an error to exclude literal meanings.

Philo of Alexandria

As he notes in Migr. Such men I for my part should blame for handling the matter in too easy and off-hand a manner: For example, an allegorical interpretation of the garment of the high priest Mos. This suggests a Jewish source. He does not hesitate to evoke some of these by name. For example, speaking about the earth in Aet. The allegorical interpretation is here based on etymology, as are those of the greatest Stoic allegorist of the imperial period, Cornutus.

Most of the time, however, he adapts classical allegorical interpretations to a Jewish context. For example, in Conf. Philo denies that this should be interpreted as a general principle of politics; under his own interpretation, it is instead a poetic reference to almighty God. In one of his most famous passages, Philo interprets the tale of Mambre, in Genesis The author reminds his readers QG 4. Since he evokes them regarding the interpretation of some Biblical difficulties, they were most likely Jewish exegetes using Stoic methods in which, at least at that time, etymology played a strong role.

Stoic allegoresis, he says,. In fact, the problem of the exact nature of Stoic allegoresis is controversial.

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Especially when mentioning the fusikoi , he himself draws upon etymology, for example, about Sara whose name in the Chaldean language i. If it is probable that in Alexandria at this time there were a great variety of allegorists blending literary, philosophical, and spiritual currents, then we can say that Philo was very skillful in drawing upon each of these. To this observation, let us add a Philonian conception of allegory that appears not to have interested later scholars: The best way to understand the meaning of this phrase is given by Plutarch when he says that Alexander, seeking the proper place for the Egyptian city destined to bear his name, had a vision Life of Alexander In it, Homer recites two verses for him in which he mentioned the island of Paros Odyssey 4.

In the latter case, Homer is not only the greatest poet but also the father of all science. In the former, it is not the poet but the exegete that unveils the meanings of dreams. And dreams sent by God always reveal something about the truth of the world. Philo is also considered the founder of negative theology in the history of monotheistic faith. Given the association of his faith with contemporary forms of Skepticism, he was also the founder of at least a kind of fideism, i.

His apparent versatility in exegesis can give the impression that his only purpose is to make philosophical themes and words coincide with the text of Bible. However, though Philo is not as systematic as Plotinus, there is much more coherence in his physics and metaphysics than one might think.

Such a hypothesis cannot be dismissed, but there is no clear evidence of its truth. In any case, negativity is, par excellence , the manner of speaking in the best way possible about God. It is not the only one; there is also the possibility of declaring His perfection and infinite glory. And metaphors, like those of monarchy, the sower, and the sun, are still different. I myself was initiated under Moses the God-beloved into his great mysteries, yet when I saw the prophet Jeremiah and knew him to be not only himself enlightened, but a worthy minister of the holy secrets, I was not slow to become his disciple.

Many other elements, especially those of the sacred banquet, resonate with the theme of the mysteries. Many scholars suggested that Philo situated himself in the Platonic tradition of philosophically transposing the Eleusinian mysteries. In this perspective, the mystery is the allegoric method itself. However, one could object to this interpretation that the meaning of a metaphor is not monolithic. It depends in great part on the identity of the addressee, about which we know little. Indeed, there was at least one ambiguity: Was he using a kind of spiritual lingua franca elaborated during the pluralistic honeymoon at the beginning of the Ptolemaic period?

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Even the man who was the closest to God, Moses, could not see Him in the Sinai. This means that without Revelation, it would be impossible to say anything about Him that bore relation with truth. At the same time, the absolute transcendence of God, as theorized by Philo, could have implied His perfect indifference to the world of matter, time, and sensibility. Yet, through His providence, God is present in the world He created. It is highly improbable, however, that philosophy had a determining role in shaping his faith and beliefs. More probable is that he perceived himself in the tradition of biblical translators, the Septuagint being so highly praised by him in the Vita Mosis.

In a time when Egypt was Ptolemaic, these translations had both political and cultural purposes. To comment upon the Bible with philosophical concepts was, in a certain way, to translate it into the language of the new cultural elite, the Roman as well as Greek. Regardless, the central idea was that the word of God had to be mediated to become accessible outside of Israel.

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From this point of view, mediation was a central Philonian concept, not only linguistically and culturally, but also ontologically: These variations were probably a means to avoid the implication that these powers had an ontological autonomy. Their nature, rather, is merely linguistic and functionalist. From a philosophical point of view, the genealogy of dunamis is incredibly rich since each great Greek philosopher used it with his own semantic specificity.

In the Bible, God is omnipotent but there is no systematic presentation of His powers. Just before the apparition of Middle Platonism, dunamis was present in Stoic doctrine, but with a more reduced range of meaning. The beneficent and the legislative powers are subordinated to them, but in Spec. Before trying to specify the relation between these powers and the logos , it is necessary to add that dunamis is not only a metaphysical term. It bears a psychological meaning as well, for example at Opif. The main problem, in human psychology as with the divine powers, lies in their relation to the logos.

It seems that Philo did his utmost to make the relation between God and the logos as complex as possible. As an example of these difficulties, in Leg. Other things, Philo adds, only exist in speech and sometimes amount to mere nothingness. In the third book of the same treatise Leg. From a philosophical point of view, if somebody remains in the world of immanence, he can refer to the universal logos , and only to him.

But to see the logos as the ultimate expression of the absolute is for Philo an absolute impiety. The Pythagorean-Platonic model of Creation acting on undefined matter is thus both preserved and richly transformed. God is unity, and only unity. It is the logos which carries in itself the principle of contraries, mixing good and evil. This leads in turn to a distinction between ontology and methodology. Anyone who divinizes the world, seeing it as the most perfect expression of the logos , is deeply wrong, since he omits God, the truly supreme genus and the only one not to have been created.

However, the theologian is, mutatis mutandis , like the biologist who today chooses some cells to place under his microscope. This act, of course, does not imply that the biologist forgets the tissue of which these cells are a part. Themes and language of immanence are for him only a means to better understand the world created by God. For a Stoic, the two formulae were strictly synonymous. The intermediary status of the logos and the many nuances in the expression of its nature do not prevent Philo from providing a more or less systematic framework. While the demiurge contemplates the Ideas in order to create the World in the Timaeus , in the De opificio , God not only creates the Ideas but organizes them into an intelligible world.

The former word refers to a Stoic concept, that of spermatikoi logoi , defined as the rational patterns inherent in the principles of organization of the world, but which Philo preferred not to use with precision. In the Quis heres , perhaps under the influence of a Stoicized interpretation of the Timaeus , Philo explains how God created the four elements from undifferentiated matter, then individual beings, by mixing these elements together.

For the Stoics, the logos and the law of Nature are perfectly synonymous. In their definition, the law of Nature is the command of the logos as to what must be done and what avoided. The vocabulary is Stoic, but with an interesting nuance: This is perhaps more than a stylistic variation; instead, it may have served to reveal a distance with regard to the canonical doctrine of the law of Nature. This distance appears to be essential, despite many variations and occasional contradictions. Last but not least, Philo emphasizes the fact that before the Torah, the patriarchs were unwritten incarnations of the law of Nature.

Admittedly, his task bordered on the impossible. He had to take into account both the historicity of the Torah and its eternity, its universality, and its institutional status as law of Israel. It is not impossible that he had in mind a model similar to the translation of the Torah into Greek. There is a plasticity of the law of Nature, at first incarnated by the patriarchs, then written; and a plasticity of the Torah, first in Hebrew, then in Greek.

At the same time, their underlying function is always the same: The De opificio was often defined as a Jewish version of the Timaeus. In this treatise, Philo proclaims, against Aristotelianism and Stoicism, that God is the unique Creator both of the models for the world and of the world itself. That does not prevent him from drawing upon patterns elaborated in the somewhat confused but rich period at the end of the first century BCE. The evaluation of the most common model of cosmological creation in the De opificio , that of an active power acting on unqualified matter, is difficult since Philo seems to affirm that God created the world ex nihilo in some passages.

It is probable that there was no significant difference between unqualified matter and pure void for him. The chief contents of the incorporeal cosmos were heaven, an invisible earth, air and void, water, spirit, and light. After the creation of the firmament and of the earth, on the fourth day God proceeded to order the heaven and to adorn it with splendid heavenly bodies.

The explanation of this fourth day is especially interesting given the following elements:. God has absolute liberty, and creates the less-important earth before the more-important celestial bodies. He knows what the then non-existent human beings will think and wants to prevent them from thinking that the movement of the celestial bodies is the cause of everything.

At this point he begins an extensive section on Pythagorean arithmology, including a meditation on the perfection of the number four. On the fifth day, God creates the living beings according to a scala naturae replete with Platonic, Aristotelian, and Stoic echoes. As has been remarked, there is a crucial difference between Plato and Philo on this point Runia Between the fishes, which are the first created, and man, crown of Creation, are birds and land animals. The creation of man, on the sixth day, is for Philo an occasion to develop some of his main themes: In fact, argues Philo, God needed no one to create the human being, but preferred that human sins not be attributed to Him.

In addition, he cites the Platonic idea of contemplation leading to philosophy, a risky idea since it could lead to such a fascination with worldly things that the Creator would be forgotten and denied, as was the case with the Chaldeans. After a long arithmologic meditation on the hebdomad, the seventh day or Shabbat, Philo arrives at original sin.

It is said that the first man the name Adam is never evoked was most excellent in his body as well as his soul. He lived in perfect harmony with nature, homeless, but the cosmos was his home and city, where he resided with complete safety. God ascribed to the first man the imposition of names, a philosophical theme with strong Platonic connotations. In the following paragraphs Philo explains his descent into wickedness by the creation of woman.

It would be absurd to deny that there are many offensive assertions regarding women in his work. Woman is the symbol of sensation, man that of reason. These problems are essential in that they deal with sexuality, ethics and ontology alike. Without trying to defend Philo systematically, one must however emphasize the first sentence of Opif. But since nothing is stable in the world of becoming, mortal beings necessarily undergo reverses and changes, the first human being too had to enjoy some ill fortune.

The first man could not eternally have a perfect life in a world which was not the intelligible one. In Stoic doctrine, the similarity between the sage and God is a permanent one. Philo is much more cautious when saying at Opif. As long as he was single, he resembled God and the cosmos in his solitariness, receiving the delineations of his soul, not all of them but as many as a mortal constitution could contain.

It is necessary in the created world and it is said in Leg. The defenders of pleasure are not absolutely wrong when they say that offspring feel an affinity with it. Their error is not in defending pleasure but in transforming its auxiliary role into the alpha and omega of ethics. He exposes all that we know about the first three, for example, that body has three dimensions and six ways of moving. But about the intellect, he says that it is absolutely unintelligible. Nothing is known about its nature, its way of arriving in the body, or its place. As with the place of heaven in the world, we are unable to say anything about it.

But in contrast with this scientific and philosophical ignorance, the Bible gives its reader true information. The intellect is a divine emanation Somn. There are grounding elements of the problem: She must, like Socrates or like Terah father of Abraham in the Torah, make a constant effort to have better self-knowledge. Socrates is the man who had no other philosophy than to know himself, while Terah is the very idea of knowing oneself. What does it mean to know oneself? The human being has no other personal good than reason.

The paradoxical aim of reason is to perceive the distance between God and His creation Somn. To know oneself does not mean to have a perfect science of what a soul is. Philo knows all the suppositions elaborated by philosophers and he uses many of them, but without ever saying that he is in possession of knowledge of the soul.

In this kind of psychology, it was not essential to know if a soul has seven components besides reason, as it is said by the Stoics, or three, like in the Platonic division, or if it contains, besides reason, nutritive and sensitive parts like in Aristotelianism. This metaphor strongly reminds us of the Stoic comparison with the octopus, but is also very different from this image. The octopus is a living unity, while the puppet master is essentially different from his puppets. The Stoic metaphor of the octopus is a monist one, but the Philonian image, inspired from Plato Laws d , is strongly dualistic.

The puppets are not even irrational beings as they are mere objects. But it is true that in Leg. There is, however, no contradiction in all this. But when he arrives to the human being at 1. A Stoic image is a good way to speak about living beings, but it is not enough when the narrative is about humans. However, it must be added that in Philo, dualistic images do not imply the division of the soul.

Such are the multi-layered levels of language Philo is capable of using at every page. For him, it is impossible to know what a human soul is, but it is not necessary to have this kind of knowledge in order to try to understand what the meaning of the word of the Lord is. To be conscious of her ignorance in the field of psychology, far from being an obstacle, actually helps to have a better perception of the limitations inherent to human nature.

But this consciousness itself necessarily rises from the confrontation of the philosophical doctrines. It would be an error to affirm that Philo despises and hates the body. Christmas concert dedicated to Dehlin. One of the musical highlights every year at Alexandria Area High School is the annual Christmas concert, and this year's version lived up to Regents approve Gabel as next U of M president. Cloudy and Windy Overnight.

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