A review of the importance of the Caribbean region in Oligo-Miocene low latitude planktonic foraminiferal biostratigraphy and the implications for modern biogeochronological schemes

Planktonic foraminifera are widely used in marine biostratigraphy thanks to their small size, limited stratigraphic range and abundance in oceanic sediments. The utility of planktonic foraminifera in biostratigraphy was first fully recognised within the Caribbean region during the middle of the 20th century. The area was critical for the subsequent development of the low latitude biostratigraphic schemes and remains fundamental for modern day biogeochronologies. This study presents a historical review of the Oligo-Miocene component of these biostratigraphic schemes, including the first proposed scheme of Cushman and Stainforth (1945) and the subsequent development. The work of Hans Bolli and Walter Blow is particularly highlighted due to their heavy influence on modern day biostratigraphy, including these authors initially recognising the biostratigraphic utility of a number of bioevents still applied today. These Caribbean-centric schemes are correlated to the modern-day low latitude biogeochronology of Wade et al. (2011), with this synthesis highlighting that a number of bioevents (e.g. Top Paragloborotalia kugleri and Top Catapsydrax dissimilis) have been applied consistently since their initial recognition. This in turn allows the recognisability of these bioevents to be deduced based on how consistently applied each datum has been. In addition, the range charts of six studies focusing heavily on the Caribbean have been reassessed to determine whether there is potential to apply a given bioevent, and the original author merely did not recognise the biostratigraphic utility of the species or favoured another bioevent. In considering this historical review, a number of amendments to Wade et al. (2011) and future priorities to planktonic foraminifera biogeochronologies are suggested. Most notably, the re-introduction of Base Globigerinatella insueta as a primary bioevent due to the historical biostratigraphic importance of this species. This event now defines early Miocene Subzone M3b (Gt. insueta/Ct. dissimilis PRZ) dividing Zone M3 into an upper Subzone M3b (Base Gt. insueta) and lower Subzone M3a (Base Globigerinatella sp.). Finally, the Miocene to Recent timescale of Wade et al. (2011) has been recalibrated following more recent updates to the magnetostratigraphy (Kochhann et al., 2016; Ogg et al., 2016; Drury et al., 2017; Beddow et al., 2018) and cyclostratigraphy (Wilkens et al., 2017). The overall effect on the planktonic foraminifera biogeochronology is minor but our results become the suggested biostratigraphic framework for the low latitudes

High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

On the Theory of Evolution Versus the Concept of Evolution: Three Observations

Here we address three misconceptions stated by Rice et al. in their observations of our article Paz-y-Miño and Espinosa (Evo Edu Outreach 2:655–675, 2009), published in this journal. The five authors titled their note “The Theory of Evolution is Not an Explanation for the Origin of Life.” First, we argue that it is fallacious to believe that because the formulation of the theory of evolution, as conceived in the 1800s, did not include an explanation for the origin of life, nor of the universe, the concept of evolution would not allow us to hypothesize the possible beginnings of life and its connections to the cosmos. Not only Stanley Miller’s experiments of 1953 led scientists to envision a continuum from the inorganic world to the origin and diversification of life, but also Darwin’s own writings of 1871. Second, to dismiss the notion of Rice et al. that evolution does not provide explanations concerning the universe or the cosmos, we identify compelling scientific discussions on the topics: Zaikowski et al. (Evo Edu Outreach 1:65–73, 2008), Krauss (Evo Edu Outreach 3:193–197, 2010), Peretó et al. (Orig Life Evol Biosph 39:395–406, 2009) and Follmann and Brownson (Naturwissenschaften 96:1265–1292, 2009). Third, although we acknowledge that the term Darwinism may not be inclusive of all new discoveries in evolution, and also that creationists and Intelligent Designers hijack the term to portray evolution as ideology, we demonstrate that there is no statistical evidence suggesting that the word Darwinism interferes with public acceptance of evolution, nor does the inclusion of the origin of life or the universe within the concept of evolution. We examine the epistemological and empirical distinction between the theory of evolution and the concept of evolution and conclude that, although the distinction is important, it should not compromise scientific logic

Effect of spirometry on intra-thoracic pressures

Due to the high intra-thoracic pressures associated with forced vital capacity manoeuvres, spirometry is contraindicated for vulnerable patients. However, the typical pressure response to spirometry has not been reported. Eight healthy, recreationally-active men performed spirometry while oesophageal pressure was recorded using a latex balloon-tipped catheter. Peak oesophageal pressure during inspiration was - 47 ± 9 cmH O (37 ± 10% of maximal inspiratory pressure), while peak oesophageal pressure during forced expiration was 102 ± 34 cmH O (75 ± 17% of maximal expiratory pressure). The deleterious consequences of spirometry might be associated with intra-thoracic pressures that approach maximal values during forced expiration

Efficacy of N-acetyl cysteine in traumatic brain injury

In this study, using two different injury models in two different species, we found that early post-injury treatment with NAcetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30-60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man

The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss

Analysis of genomic resources available for cnidarians revealed that several key components of the vertebrate innate immune repertoire are present in representatives of the basal cnidarian class Anthozoa, but are missing in Hydra, a member of the class Hydrozoa, indicating ancient origins for many components of the innate immune system

Origin of symbol-using systems: speech, but not sign, without the semantic urge

Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint

Risk and sensitivity quantification of fracture failure employing cohesive zone elements

Many structures are subjected to the risk of fatigue failure. For their reliability-based design, it is thus important to calculate the probability of fatigue failure and assess the relative importance of the involved parameters. Although various studies have analyzed the fatigue failure, the stage of fracture failure has been less focused. In particular, the risk analysis of fracture failure needs to be conducted considering its importance in actual structures. This article proposes a new probabilistic framework for the risk and sensitivity analysis of structural fatigue failure employing cohesive zone elements. The proposed framework comprises three steps, namely finite element analysis using cohesive zone elements, response surface construction, and risk and sensitivity analysis of fatigue failure, which require several mathematical techniques and algorithms. The proposed framework is tested by applying it to an illustrative example, and the corresponding analysis results of fracture failure probability with different threshold values of a limit-state function are presented. In addition, the sensitivities of failure risk with respect to the statistical parameters of random variables are presented and their relative importance is discussed