Greenhouse?icehouse transition in the Late Ordovician marks a step change in extinction regime in the marine plankton

Two distinct regimes of extinction dynamic are present in the major marine zooplankton group, the graptolites, during the Ordovician and Silurian periods (486−418 Ma). In conditions of “background” extinction, which dominated in the Ordovician, taxonomic evolutionary rates were relatively low and the probability of extinction was highest among newly evolved species (“background extinction mode”). A sharp change in extinction regime in the Late Ordovician marked the onset of repeated severe spikes in the extinction rate curve; evolutionary turnover increased greatly in the Silurian, and the extinction mode changed to include extinction that was independent of species age (“high-extinction mode”). This change coincides with a change in global climate, from greenhouse to icehouse conditions. During the most extreme episode of extinction, the Late Ordovician Mass Extinction, old species were selectively removed (“mass extinction mode”). Our analysis indicates that selective regimes in the Paleozoic ocean plankton switched rapidly (generally in <0.5 My) from one mode to another in response to environmental change, even when restoration of the full ecosystem was much slower (several million years). The patterns observed are not a simple consequence of geographic range effects or of taxonomic changes from Ordovician to Silurian. Our results suggest that the dominant primary controls on extinction throughout the lifespan of this clade were abiotic (environmental), probably mediated by the microphytoplankton.The importance of the marine plankton in both the carbon cycle and in the food web that supports the diversity of marine life is undisputed. However, the evolutionary dynamics of planktic species and the factors controlling their diversity and evolutionary turnover are still poorly known (1, 2). This is particularly so for the Paleozoic, where problems of preservation and sampling bias, and poor time resolution, have precluded detailed analysis. How does the marine plankton respond to environmental perturbations arising from climate change over geological time? How does background extinction differ from episodic and mass extinction in the pelagic realm? Is the risk of plankton species extinction dependent on the amount of time since the species originated (3)? These questions have important implications for macroevolutionary process, stability of marine ecosystems, and modern biodiversity conservation (3–5). Here, using a new global data set of unparalleled temporal resolution, we attempt to answer these questions.The graptoloid clade (order Graptoloidea) constituted the main component of the early Paleozoic macrozooplankton from the beginning of the Ordovician to the Early Devonian (6). Graptoloids were colonial filter-feeding protochordates, generally ranging from a few millimeteres up to ∼200 mm in maximum dimension, which lived suspended in the water column in a range of depth zones. They have been used extensively for correlation and zonation (7–10), and the stratigraphic distributions of species are well documented. Thus, their observed stratigraphic ranges commonly are inferred to be good approximations of their true ranges in time, and empirical graptoloid range data have been used as examples of, or tests for, macroevolutionary rates (3, 4, 11–13). Like most of the marine macroplankton, their evolutionary dynamics are interpreted to have depended closely on those of the microphytoplankton and bacterioplankton (13–16), the primary producers in the food web and which, in the modern oceans, are sensitive indicators of oceanic circulation, nutrient flux, and global climate (1, 17); in addition, they depended on physical properties of the water mass such as temperature and chemistry.Most previous studies of taxonomic survivorship using the fossil record have been limited by the relatively coarse time resolution of the analyses, generally no better than 7- to 11-My time bins (5, 18–20). We use the constrained optimization (CONOP) global graptolite composite developed by Sadler et al. (10) that has been calibrated directly by radiometric dating and provides the basis for the Ordovician and Silurian global time scales (21). This composite has been constructed from >18,000 local records of the stratigraphic ranges of 2,045 species in 518 published stratigraphic sections distributed globally; it resolves 2,031 discrete temporal levels through the 74-My span of the graptoloid clade, yielding a mean resolution of 37 kya between levels (13). The first- and last-appearance events of all species in all sections have been used to optimally order, and proportionally space in time, the earliest first appearance and latest last appearance of each taxon using a simulated annealing optimization heuristic (10, 22) (see SI Text, Construction of the Global Composite Sequence). The raw extinction and origination rates of the 2,045 graptolite species have been smoothed with a 0.25-My moving window centered at each resolved level, providing, in effect, instantaneous rate curves, each with 2,031 control points. Extinction and origination rates, and the derivative measures such as faunal turnover (origination + extinction), have thus been estimated with a precision that is orders of magnitude better than in most previous studies of global extinction. Uncertainty bounds have been estimated by bootstrapping. Our data set spans the entire lifespan of the graptoloid clade; the uppermost part, in the earliest Devonian, is omitted from further analysis because species diversity is very low and analytical uncertainty becomes unacceptably large. For similar reasons, the basal 4 My of the clade history is not included in the analysis.To test if extinction depends on species age, we use taxon survivorship of birth cohorts (23) (Fig. 1A) and AIC-based model selection (Figs. S1–S6). Birth cohorts are comprised of all species originating in a short interval of time; we use time bins of 0.25 million years, 0.5 million years, and 1 million years. A survivorship curve, produced by plotting the age of species in a cohort against the proportion of species still extant as the cohort decays over time, is exponential when the probability of extinction is uniform through the life of the cohort. In a semilog plot, this results in a linear distribution (3) (Fig. 1A, β = 1). Significant deviations from an exponential relationship indicate age dependency of extinction and yield curves in semilog space that are either convex up or concave up, which are approximated by Weibull distributions with shape parameters (β-values) greater than or less than unity, respectively (24). A concave-upward curve indicates a decreasing extinction probability with species age (Fig. 1A, β < 1). A convex-upward curve indicates increasing extinction probability with taxon age (Fig. 1A, β > 1). To produce Fig. 2C, on which each cohort is represented by a single point plotted at its β-value, we varied the cohort durations and start times in successive iterations using time bin durations of 0.25 million years, 0.5 million years, and 1 million years, and offsets of bin start equal to one-fifth of the bin duration. This produces, in effect, a series of moving windows of different duration and boundary ages, and, for this reason, points shown are not statistically independent of each other. This approach, however, maps out patterns of survivorship that are robust to arbitrary variations in cohort size and start time, and robust results are indicated by clustering of points in the figure. In contrast, isolated points in the plot are idiosyncratic to a particular combination of bin duration and starting time, and are ignored during subsequent interpretation. Gaps in coverage indicate intervals where species richness is low and cohorts fail to meet the qualifying threshold of at least 20 taxa.Open in a separate windowFig. 1.(A) Semilog plot showing idealized taxon survivorship curves for a cohort commencing at 0 My; β = 1, linear survivorship curve indicating exponential decay rate (constant extinction probability); β < 1, decreasing decay rate, extinction probability decreases with taxon age; β > 1, increasing decay rate, extinction probability increases with taxon age). Black dots indicate median cohort age in each curve. (B−D) General age structure curves for all species (B) and for all Ordovician and all Silurian species (C and, detail, D). The life expectancy of a Silurian species is half that of an Ordovician species.Open in a separate windowFig. 2.(A) Graptoloid standing species richness, main families shown. The white line is level-by-level generic richness. (B) Extinction rate (extinctions per lineage-million-years), 0.25-My moving window, centered at each level in the composite. The band represents ±1 SE from bootstrap means (1,000 iterations) of median values for each 0.25-My bin. The main extinction episodes, those exceeding the 75th percentile for each period (dashed lines) are: La2bEE, Lancefieldian 2; Da3EE, Darriwilian 3; Da4EE, Darriwilian 4; EaEE, Eastonian; BoEE, Bolindian; HiEE, Hirnantian; RhuEE, Rhuddanian; AerEE, Aeronian; ShEE, Sheinwoodian; HomEE, Homerian; Lu1EE, Ludfordian (early); Lu2EE, Ludfordian (late); and PriEE, Pridolian. (C) Weibull shape (β) value for each cohort survivorship curve is plotted at the median age, in geological time, of the last appearances of its constituent species. Red points, Weibull model preferred; green points, exponential model preferred; the darker the tone, the greater the AIC weight of the preferred model. Age bands with clusters of green points indicate fields with cohorts in which extinction is not dependent on species age; 498 points are shown.Open in a separate windowFig. S1.Examples of model fits for individual cohorts taken from our data. In all cases, the green curve is the best-fit exponential distribution, the red curve is the best-fit Weibull distribution, and the heavier line indicates the favored fit. “Weight” indicates Akaike weight of the best-fitting model. (A) Cohort for which an exponential fit is favored. (B) Cohort for which there is no preferred fit. (C) Cohort for which a Weibull fit, with shape parameter β > 1, is favored. (D) Cohort for which a Weibull fit, with β < 1, is favored.Open in a separate windowFig. S6.Test of the impact of uneven distribution of first appearances. Time series of fitted Weibull shape parameters (β) for the graptolite data, superimposed on gray-scale map of fitted β from data in which observed durations have been randomized with respect to observed first-appearance ages; density of gray shading is proportional to density of points. Dashed lines are the one-tailed, 95% and 99% quantiles on the distribution of the randomized data; fluctuations in the levels of these lines are a consequence of uneven distribution of first-appearance ages in time. See Fig. 2 for explanation of symbol colors, etc.     

Does fundoplication change the risk of esophageal cancer in the setting of GERD?

The effect of a surgical antireflux procedure on the risk of cancer in those with GERD and Barrett's esophagus is unclear. Although some authorities have suggested that a surgical antireflux procedure might be superior to medical management for the prevention of cancer, the cumulative data do not demonstrate that those patients undergoing surgery have any decrement in cancer risk compared to those who receive medication. Most data available to assess the effect of surgery on cancer risk come from case series. These data are of very limited utility, because of differences in the baseline composition of groups undergoing medical and surgical therapy. Until more data are available, patients should not be advised to undergo surgical fundoplication as an antineoplastic measure.     

Abrupt climate change in the computer: is it real?

Models suggest that dramatic changes in the ocean circulation are responsible for abrupt climate changes during the last ice age and may possibly alter the relative climate stability of the last 10,000 years.     

Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization’s goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post–HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post–HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.     

Can SPECT change the surgical strategy in patients with primary hyperparathyroidism?

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in outpatients. It is more common in females, after menopause, and the prevalence is 1 to 4:1000 in the general population. Patients with PHPT have abnormal regulation of PTH secretion, resulting in elevated serum calcium and inappropriately high or normal PTH in relation to the calcium value. Sporadic PTH-secreting adenoma alone accounts for 90% of cases of PHPT, while multiglandular hyperplasia is more common in familial hyperparathyroidism syndromes (5%) and parathyroid carcinomas represent less than 1% of cases. Only after making sure there is functional autonomy of one or more parathyroid glands, localization imaging tests should be performed to guide a possible surgical procedure. It is important to highlight that these tests have limitations and can yield false-positive and false-negative results. There are cases in which the parathyroid gland is difficult to be located, requiring a combination of imaging methods for pre-operative localization, such as (99m)Tc-pertechnetate, SPECT, SPECT/CT, and US. We describe the case of a 50-year-old female patient diagnosed with PHPT, who underwent a surgical procedure without success, with maintenance of hypercalcemia and hyperparathyroidism. In this case, the hyperfunctioning parathyroid was located in the retrotracheal region only after scintigraphy combined with SPECT/CT were used.     

Does ALLHAT change the management of hypertension in chronic kidney disease?

ALLHAT was designed to test the hypothesis that “newer” antihypertensive agents are superior to a thiazide diuretic for cardiovascular outcomes. Pre-specified secondary outcomes included the development of endstage renal disease (ESRD) (dialysis, renal transplantation, or death from renal cause) and estimated glomerular filtration rate (GFR). ALLHAT showed no differences in the overall rates of ESRD between those randomized to chlorthalidone, amlodipine, or lisinopril. It showed a slower rate of decline of GFR among those randomized to amlodipine in both diabetics and nondiabetics, and in the composite end point (ESRD or ≥ 50% decline in GFR) in nondiabetics. The results of ALLHAT are consistent with other studies that, for the patient population studied (presumably largely nonalbuminuric patients with and without diabetes), at systolic BP < 130 mm Hg, there is no difference for renal outcomes between a thiazide diuretic, dihydropyridine calcium channel blocker, and ACEI-initiated treatment for 5 to 6 years of follow-up. These results suggest that BP control per se remains the most important objective for this patient population.     

Can OCT change the therapeutic strategy in ACS due to plaque erosion?

The pathophysiology of acute coronary syndromes was thought to be coronary thrombosis over a plaque rupture. Autopsy studies revealed that not all cases were due to plaque rupture, even denuded endothelium or calcific nodule can beget a thrombus. Introduction of OCT made, in vivo recognition of lesion morphology clear. Plaque ruptures are most common and need primary angioplasty. Recent studies established plaque erosion is responsible for ACS in one third of the cases and majority of them present as Non ST elevation myocardial infarction and commonly found in young patients without major risk factors. Evidence from recent studies suggested that stenting can be deferred and they can be managed conservatively with good long term outcomes. More randomized trials are needed comparing plaque rupture and plaque erosion as regards conservative versus invasive management. If these studies substantiate the concept of conservative management, it will lead to a paradigm shift in their management.     

Time to change the glomerular filtration rate estimating formula in primary care?

BackgroundThe most commonly used equation for estimated glomerular filtration rate (eGFR) is nowadays the four-variable Modification of Diet in Renal Disease (MDRD) equation. This formula was derived from patients with non-diabetic chronic kidney disease (CKD) with mean GFR 40 ml/min.MethodsWe compared the MDRD study equation and the recently developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation by applying the two formulas in 1747 middle-aged cardiovascular risk persons in primary care.ResultsThe prevalence of renal insufficiency defined as eGFR < 60 ml/min was 6.7% (95% CI 5.6–8.0) according to the MDRD formula, and 3.6% (95% CI 2.8–4.6) according to the CKD-EPI formula. The subjects who were classified as having CKD according to the MDRD equation, but no-CKD according to the CKD-EPI formula, were mostly women (86%) and slightly younger than the subjects having CKD according to both formulas.ConclusionThe characteristics of the subjects commonly treated in primary care resemble more closely the population from which the CKD-EPI than the MDRD study equation was derived from. Thus, we suppose that in general practice, the CKD-EPI equation is more suitable for estimating renal function than the MDRD equation.