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Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified.
All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted.
One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3.
In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.
Treatment of hypoplastic left heart syndrome varies across institutions. This study examined the impact of introducing a standardised programme.
This retrospective cohort study evaluated the effects of a comprehensive strategy on 1-year transplant-free survival with preserved ventricular and atrioventricular valve (AVV) function following a Norwood operation. This strategy included standardised operative and perioperative management and dedicated interstage monitoring. The post-implementation cohort (C2) was compared to historic controls (C1). Outcomes were assessed using logistic regression and Kaplan–Meier analysis.
The study included 105 patients, 76 in C1 and 29 in C2. Groups had similar baseline characteristics, including percentage with preserved ventricular (96% C1 versus 100% C2, p = 0.28) and AVV function (97% C1 versus 93% C2, p = 0.31). Perioperatively, C2 had higher indexed oxygen delivery (348 ± 67 ml/minute/m2 C1 versus 402 ± 102ml/minute/m2 C2, p = 0.015) and lower renal injury (47% C1 versus 3% C2, p = 0.004). The primary outcome was similar in both groups (49% C1 and 52% C2, p = 0.78), with comparable rates of death and transplantation (36% C1 versus 38% C2, p = 0.89) and ventricular (2% C1 versus 0% C2, p = 0.53) and AVV dysfunction (11% C1 versus 11% C2, p = 0.96) at 1-year. When accounting for cohort and 100-day freedom from hospitalisation, female gender (OR 3.7, p = 0.01) increased and ventricular dysfunction (OR 0.21, p = 0.02) and CPR (OR 0.11, p = 0.002) or ECMO use (OR 0.15, p = 001) decreased the likelihood of 1-year transplant-free survival.
Standardised perioperative management was not associated with improved 1-year transplant-free survival. Post-operative ventricular or AVV dysfunction was the strongest predictor of 1-year mortality.
The Indian residential school (IRS) system in Canada ran for over a century until the last school closed in 1996. Conditions in the IRSs resulted in generations of Indigenous children being exposed to chronic childhood adversity. The current investigation used data from the 2008–2010 First Nations Regional Health Survey to explore whether parental IRS attendance was associated with suicidal thoughts and attempts in childhood, adolescence and in adulthood among a representative sample of First Nations peoples living on-reserve across Canada. Analyses of the adult sample in Study 1 (unweighted n=7716; weighted n=186,830) revealed that having a parent who attended IRS was linked with increased risk for suicidal thoughts and attempts in adolescence and adulthood. Although females were negatively affected by having a parent who attended IRS, the link with suicidal ideation in adulthood was greater for males. Analyses of the youth sample in Study 2 (unweighted n=2883; weighted n=30,190) confirmed that parental IRS attendance was associated with an increased risk for suicidal ideation and attempts. In contrast to the adult sample, parental IRS attendance had a significantly greater relation with suicidal ideation among female youth. A significant interaction also emerged between parental IRS attendance and age in the youth sample, with the influence of parental attendance being particularly strong among youth ages 12–14, compared with those 15–17 years. These results underscore the need for culturally relevant early interventions for the large proportions of Indigenous children and youth intergenerationally affected by IRSs and other collective traumas.
These theorems take off from Condorcet, who discovered cycles, rather than Arrow, who had nothing to say about cycles. They directly generalize the Paradox of Voting, in proof as well as content. The most general of them states a sufficient condition for cycles that is demonstrably as general as possible, necessary as well as sufficient.
One lesson of the Paradox of Voting is that social-choice procedures sometimes flout social rationality: they do not fulfill the conditions of rationality long assumed for individual choice. The rough idea is that a rational individual always makes a most preferred choice, but a society cannot when the social preference is cyclic. In a way, Arrow’s celebrated Impossibility Theorem generalizes this lesson—but not the Paradox of Voting, as is too often alleged. It does show that certain modest assumptions force a breakdown in the transitivity of either social preference or social indifference, the beat or tie relation, but that is consistent with the absence of cycles. Even so, Arrow’s Theorem can be turned into a generalization of the Paradox of Voting. For we can add a bit to his assumptions and get a cycle. The next chapter shows how.
Of the normative questions occasioned by the Paradox of Voting, the most obvious is Condorcet’s: What is the best election rule? It is still the chief question that exercises some of the foremost theorists of voting and social choice. Two more questions are likewise rooted in intellectual history, but this time nineteenth century utilitarian philosophy and economics: Can social choice be based on interpersonally comparable cardinal utility, or preference intensity? And is social welfare its proper object? Another question is what cycles assume and what, if anything, they imply about the rationality of individuals. A final question is whether, despite challenges to classical rationality, there is a fully general way to do what everyone instinctively wishes to do: make best choices from sets that are somehow unproblematically available.
Although cycles are not maladies to be prevented or cured, nor misfortunes to be avoided or regretted, they do raise hard questions, positive and normative. The most salient positive question is how to predict outcomes when every feasible alternatives is dominated, or beaten by another – how, in other words, to generalize the core to a predictive set that is never empty. Another is how to explain so much apparent stability in the face of cycles – the durability of real social choices.
If we add a bit to AUD̸I we can deduce that ≻ flouts not only T but Acyclicity – that ≻p is sometimes cyclic. In other words, one can turn Arrow’s Theorem into a generalization of the Paradox of Voting. There are several ways to do that, and one of them allows interpersonal comparisons of preference intensity.
Following Arrow and the classical framework of rational choice, we have allowed the set of feasible alternatives to vary, and in one way that has weakened results: a cycle blocks any stable or unbeaten choice from some subset of A, some potential feasible set, but not necessarily from any given set. However, we can reframe those results so that A is no longer the universe of alternatives but instead comprises the feasible alternatives on any given occasion. Besides strengthening old results in one way, that will give us a more flexible framework in which to discuss the strategic consequences of cycles in the next chapter.
How common or exotic are cycles and instability? Which patterns of voter preference produce or prevent them? Some deductive results suggest that the cycle-prone patterns are rare, others that they abound. Although well-known results of the latter sort have been over-interpreted, in the end we must conclude that the Paradox of Voting is far from exotic. It is here that I discuss stability in one dimension, its breakdown in two or more, issue packaging, and the misuse of observational evidence.
Social choice depends not only on preferences and procedure but on strategy, on how voters choose to act and interact to achieve desired outcomes, and that depends on cycles. Cycles make social choice manipulable: they block any general incentive to vote sincerely and instead create opportunities for single voters to profit from the strategic mis-statement of their preferences. We can generalize that consequence a bit and deduce a more sweeping result about social choice procedures that are nonmanipulable, or strategy-free: if they are not purely dictatorial or preposterously irresolute they do not exist. Besides ensuring manipulability, cycles block the implementability of social choice procedures by game solutions of the simplest, most prominent sorts: core outcomes and Nash equilibria.
Besides voter strategy, cycles affect procedural structure, how the process of social choice is organized before anyone gets to vote. One way is by making outcomes highly dependent on the fine details of legislative agendas. That can happen in quite a variety of ways – in the sequence and interdependence of pairwise votes, in the membership of feasible sets, and in the joining or dividing of “questions,” or agenda items. Sometimes cycles also turn the apparent asset of veto (or concurrence) power – the power that ties together the parts of government in a separated-powers system – into a liability, a bad thing merely to possess. And cycles create the incentive to form political parties.