Gestational age at initiation of 17-alpha hydroxyprogesterone caproate and recurrent preterm birth

Background Preterm birth is the leading cause of neonatal morbidity and mortality in nonanomalous neonates in the United States. Women with a previous early spontaneous preterm birth are at highest risk for recurrence. Weekly intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent prematurity. Although current guidelines recommend 17-alpha hydroxyprogesterone caproate initiation between 16 and 20 weeks, in clinical practice, 17-alpha hydroxyprogesterone caproate is started across a spectrum of gestational ages. Objective The objective of the study was to examine the relationship between the gestational age at 17-alpha hydroxyprogesterone caproate initiation and recurrent preterm birth among women with a prior spontaneous preterm birth 16–28 weeks’ gestation. Study Design This was a retrospective cohort study of women from a single tertiary care center, 2005–2016. All women with ≥1 singleton preterm births because of a spontaneous onset of contractions, preterm prelabor rupture of membranes, or painless cervical dilation between 16 and 28 weeks followed by a subsequent singleton pregnancy treated with 17-alpha hydroxyprogesterone caproate were included. Women were grouped based on quartiles of gestational age of 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 140/7 to 161/7; quartile 2, 162/7 to 170/7; quartile 3, 171/7 to 186/7; and quartile 4, 190/7 to 275/7). Women with a gestational age of 17-alpha hydroxyprogesterone caproate initiation in quartiles 1 and 2 were considered to have early-start 17-alpha hydroxyprogesterone caproate; those in quartiles 3 and 4 were considered to have late-start 17-alpha hydroxyprogesterone caproate. The primary outcome was recurrent preterm birth <37 weeks’ gestation. Secondary outcomes included recurrent preterm birth <34 and <28 weeks’ gestation and composite major neonatal morbidity (diagnosis of grade III or IV intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis stage II or III, or death). Gestational age at delivery was compared by quartile of 17-alpha hydroxyprogesterone caproate initiation using Kaplan-Meier survival curves and the log-rank test. Logistic regression models estimated odds ratios for the association between gestational age at 17-alpha hydroxyprogesterone caproate initiation and preterm birth <37 weeks’ gestation, adjusting for demographics, prior pregnancy and antenatal characteristics. Results A total of 132 women met inclusion criteria; 52 (39.6%) experienced recurrent preterm birth <37 weeks in the studied pregnancy. 17-Alpha hydroxyprogesterone caproate was initiated at a mean 176/7 ± 2.5 weeks. Demographic and baseline characteristics were similar between women with early-start 17-alpha hydroxyprogesterone caproate (quartiles 1 and 2) compared with those with late-start 17-alpha hydroxyprogesterone caproate (quartiles 3 and 4). Women with early-start 17-alpha hydroxyprogesterone caproate trended toward lower rates of recurrent preterm birth <37 weeks compared with those with late-start 17-alpha hydroxyprogesterone caproate (41.3% vs 57.7%, P =.065). Delivery gestational age was inversely proportional to gestational age at 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 374/7 weeks vs quartile 2, 365/7 vs quartile 3, 361/7 weeks vs quartile 4, 340/7, P =.007). In Kaplan-Meier survival analyses, these differences in delivery gestational age by 17-alpha hydroxyprogesterone caproate initiation quartile persisted across pregnancy (log-rank P <.001). In regression models, later initiation of 17-alpha hydroxyprogesterone caproate was significantly associated with increased odds of preterm birth <37 weeks. Women with early 17-alpha hydroxyprogesterone caproate initiation also had lower rates of major neonatal morbidity than those with later 17-alpha hydroxyprogesterone caproate initiation (1.5% vs 14.3%, P =.005). Conclusion Rates of recurrent preterm birth among women with a prior spontaneous preterm birth 16–28 weeks are high. Women beginning 17-alpha hydroxyprogesterone caproate early deliver later and have improved neonatal outcomes. Clinicians should make every effort to facilitate 17-alpha hydroxyprogesterone caproate initiation at 16 weeks

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Parting with illusions in evolutionary ethics

I offer a critical analysis of a view that has become a dominant aspect of recent thought on the relationship between evolution and morality, and propose an alternative. An ingredient in Michael Ruse's 'error theory' (Ruse 1995) is that belief in moral (prescriptive, universal, and nonsubjective) guidelines arose in humans because such belief results in the performance of adaptive cooperative behaviors. This statement relies on two particular connections: between ostensible and intentional types of altruism, and between intentional altruism and morality. The latter connection is problematic because it makes morality redundant, its role having already been fulfilled by the psychological dispositions that constitute intentional altruism. Both behavioral ecology and moral psychology support this criticism, and neither human behavioral flexibility nor the self-regard / other-regard distinction can provide a defense of the error theory. I conclude that morality did not evolve to curb rampant selfishness; instead, the evolutionarily recent 'universal law' aspect of morality may function to update behavioral strategies which were adaptive in the paleolithic environment of our ancestors (to which our psychological dispositions are best adapted), by means of norms more appropriate to our novel social environment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42482/1/10539_2004_Article_5102509.pd

UNDECIDABILITY OF PDL WITH L=(A2I/I-GREATER-THAN-OR-EQUAL-TO-O)

The ability of whole ecosystems to respond to selection has recently been demonstrated in artificial selection experiments, (Swenson et al 2000a, Swenson et al 2000b). As well as having wide-ranging practical applications, this result significantly broadens the application of theoretical concepts of the mechanisms of heritability and variation in biological systems. Simulation models have the potential to be useful tools for the investigation of these issues. Whilst related simulation work exists (Ikegami 2001, Wilson 1992), ecosystem-level selection itself has yet to be modelled. This paper presents such a model, in which ecosystems are modelled as generalised Lotka-Volterra systems and are subject to a generational selection process. A positive response to selection for diversity is demonstrated, with the only sources of variation being sampling errors arising when 'offspring' ecosystems are produced