How to improve infraorbital hollows with neuromodulators-A clinical prospective interventional study about the application of facial biomechanics.

BACKGROUND: A previous injection algorithm termed the "Toxin Lift" was recently introduced and described volume increases in the midface following neuromodulator treatments of the jawline. Increase in midfacial volume due to soft tissue repositioning could also affect the severity of infraorbital hollows. OBJECTIVE: The objective is therefore to evaluate whether the severity of infraorbital hollows can be improved by injecting neuromodulators in the supra-mandibular segment of the platysma. MATERIALS AND METHODS: A total of 35 volunteers (11 males/24 females) with a mean age of 39.8 (9.6) years and a mean BMI of 25.2 (5.2) kg/m2 were investigated. Bilateral infraorbital regions were evaluated via clinical assessment and semi-quantitative 3D imaging. The applied injection technique targeted the platysma via four injection points administering 5 I.U. per injection point resulting in a total of 20 I.U. per facial side. RESULTS: Volume increase of the infraorbital region was 0.13 cc at 15 days (p = 0.001) and was 0.02 cc at 30 days (p = 0.452) whereas the skin displacement in cranial direction was 0.54 mm at 15 days (p < 0.001) and was 0.31 mm at 30 days (p < 0.001). Clinical evaluation revealed a highly statistically significant improvement of the tear trough, palpaebromalar groove, and of the lid-cheek junction when compared to baseline with all p < 0.001. CONCLUSION: The results of this clinical prospective interventional analysis revealed that the "Toxin Lift" injection technique is capable to improve the clinical appearance of infraorbital hollows. The effects can be explained by the concepts of facial biomechanics.

Facial Soft Tissue Repositioning With Neuromodulators: Lessons Learned From Facial Biomechanics.

BACKGROUND: Neuromodulators have proven efficacy in reducing facial rhytides and have also been reported to improve jawline contour and the appearance of platysmal bands. Lifting effects of the tail of the eyebrow are expected outcomes when targeting the lateral periorbital region, underscoring the versatility of neuromodulator treatments. OBJECTIVES: The aim of this study was to analyze the clinical effectiveness of a novel neuromodulator-based injection algorithm with regards to its ability to reposition the middle and lower facial soft tissues. METHODS: Seventy-five study participants (8 males, 67 females) with a mean [standard deviation] age of 37.5 [8.5] years were injected with neuromodulators in the subdermal plane of the mandibular soft tissues following a standardized algorithm. Live rating of clinical appearance was performed, as well as volume change and skin vector displacement measured by 3-dimensional imaging at baseline, Day 14, and Day 30. RESULTS: Three-dimensional volume analysis revealed an increase in midfacial volume by 0.46 mL, and a decrease of the lower facial volume by 0.30 mL compared with baseline. Additionally, an improvement of midfacial fullness (by 0.13) and jawline contour (by 0.44) was reported on clinical rating scales at Day 30 compared with baseline. CONCLUSIONS: Facial soft tissues can be repositioned during the 30-day follow-up period following a neuromodulator treatment; this was reflected through an increase in midfacial volume as well as through a decrease in lower facial volume. The novel injection algorithm presented can provide a safe and effective option for patients desiring improvement of midfacial fullness and jawline contour with neuromodulator treatment alone.

Coral reef-associated bryozoans of Jamaica.

As part of a long-term ecological study of the cryptic comunity of Jamaican coral reefs carried out by Jeremy B.C. Jackson and associates during the 1970s and early 1980s, collections were made of reef bryozoans found at 14 sites around the island. Space occupied by bryozoans on undercoral surfaces is dominated by relatively few species. However, during scanning electrone microscopy study and monograph preparation a diverse assortment of relatively rare species was discovered. Of the 132 species found, 56%, 74 species (70 cheilostomes and 4 cyclostomes) are new, as are one family (Inversiscaphidae) and 5 genera (Planospinella, Caribaria, Spirocoleopora, Gemellitheca, and Palliocella).

The Influence of Different Light Angles During Standardized Patient Photographic Assessment on the Aesthetic Perception of the Face.

BACKGROUND: 2D baseline and follow-up clinical images are potentially subject to inconsistency due to alteration of imaging parameters. However, no study to date has attempted to quantify the magnitude by which such images can be influenced. OBJECTIVE: The objective of the present study is to identify the magnitude by which images can be influenced by changing the imaging light angle. METHODS: This study is based on the evaluation of 2D frontal images of the face and included a total of 51 subjects of which n = 14 were males and n = 37 were females. Faces were photographed at 0°, 30°, and 60° light angle under identical and standardized conditions. Images were randomized and rated by 27 blinded raters for age, facial attractiveness, body mass index (BMI), temporal hollowing, lower cheek fullness, nasolabial sulcus severity, and jawline contour. RESULTS: Facial attractiveness decreased, facial unattractiveness increased and the evaluated BMI (based on facial assessment) increased statistically significantly at 60°. The assessment of regional facial scores, i.e., temporal hollowing, lower cheek fullness, and jawline contour, showed no statistically meaningful changes both at 30° and at 60° light angle. CONCLUSION: The results indicate that there might be an observed blind range in light angle (0°-30°) which does not influence facial assessment. Increasing the light angle past the threshold value to 60° might result in a statistically significant impact on facial perception which should be accounted for when documenting and/or presenting facial 2D images. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

After the Temporal Lifting Technique-What comes next?

BACKGROUND: The temporal lifting technique can provide lateral facial lifting when administering hyaluronic acid (HA)-based soft tissue fillers into the subdermal plane of the temple. However, the central facial oval is not influenced by this technique. OBJECTIVES: To identify the safety and esthetic effectiveness of additional midfacial injection points (in addition to the temporal lifting technique) that can volumize the medial midface, lift the lateral face, and increase jawline contouring when included into a full-face injection algorithm. METHODS: The patient records of nine consecutive patients (all females) with a mean age of 35.0 (8.4) years and a mean body mass index of 21.7 (2.4) kg/m2 were retrospectively analyzed after a full-face injection algorithm was performed using HA-based fillers. The additional injection points target the supraperiosteal plane of the medial zygomatic arch, the lateral infraorbital region, and the pyriform fossa using both needles and cannula. RESULTS: No adverse events were observed during the 6-month retrospective observational period. The volume of the medial midface increased, the volume of the lateral midface decreased, and the contour of the jawline improved; all effects reached a highly statistically significant level with p < 0.001. CONCLUSION: Despite each individual injection is currently performed on a daily clinical basis the evaluated injection algorithm following the temporal lifting technique shows some evidence that it is safe and esthetically effective. Future studies will need to confirm the results presented herein in a larger sample and with objective outcome measures to guide safe and effective esthetic outcomes.

Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan.

While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number.

Urethrogram: Does Postoperative Contrast Extravasation Portend Stricture Recurrence?

OBJECTIVE: To demonstrate our hypothesis that the presence of extravasation on postoperative urethrogram is inconsequential for disease recurrence in urethroplasty postoperative follow-up. MATERIALS AND METHODS: We utilized the Trauma and Urologic Reconstructive Network of Surgeons database to assess 1691 patients who underwent urethroplasty and post-operative urethrogram. Anatomic and functional recurrence were defined as <17 Fr stricture documented at 12-month cystoscopy and need for a secondary procedure during 1 year of follow-up, respectively. Our primary outcomes were the sensitivity and positive predictive value of post-operative urethrogram for predicting anatomic and functional recurrence of urethral stricture disease. RESULTS: Among 1101 patients with cystoscopy follow-up, 54 (4.9%) had extravasation on initial postoperative urethrogram. Among those 54, 74.1% developed an anatomic recurrence vs 13% without extravasation (P <.001). Similarly, functional recurrence was 9.3% with extravasation vs 3.2 % without extravasation (P = .04). Patients with extravasation more often reported a postoperative urinary tract infection (12.9% vs 2.7%; P <.01) or wound infection (7.4% vs 2.6%; P = .04). Sensitivity of postoperative urethrogram in predicting any recurrence was 27.3%, specificity 98.7%, positive predictive value 77.8%, and negative predictive value 89.3%. Fourty-five of 54 patients with extravasation had a recurrence of some kind, equating to a 22.2% urethroplasty success rate at 1 year. CONCLUSION: Postoperative urethrogram has a high specificity but low sensitivity for anatomic and functional recurrence during short term follow-up. The positive predictive value of urinary extravasation is high: patients with extravasation incur a high risk of anatomic recurrence within 1 year and such patients may warrant increased monitoring.

How colonial animals evolve.

The evolution of modular colonial animals such as reef corals and bryozoans is enigmatic because of the ability for modules to proliferate asexually as whole colonies reproduce sexually. This reproductive duality creates an evolutionary tension between modules and colonies because selection operates at both levels. To understand how this evolutionary conflict is resolved, we compared the evolutionary potential of module- and colony-level traits in two species of the bryozoan Stylopoma, grown and bred in a common garden experiment. We find quantitatively distinct differences in the evolutionary potential of modular and colony traits. Contrary to solitary organisms, individual traits are not heritable from mother to daughter modules, but colony traits are strongly heritable from parent to offspring colonies. Colony-level evolution therefore dominates because no evolutionary change can accumulate among its modules.

Evolutionary Determinants of Morphological Polymorphism in Colonial Animals.

Colonial animals commonly exhibit morphologically polymorphic modular units that are phenotypically distinct and specialize in specific functional tasks. But how and why these polymorphic modules have evolved is poorly understood. Across colonial invertebrates, there is wide variation in the degree of polymorphism, from none in colonial ascidians to extreme polymorphism in siphonophores, such as the Portuguese man-of-war. Bryozoa are a phylum of exclusively colonial invertebrates that uniquely exhibit almost the entire range of polymorphism, from monomorphic species to others that rival siphonophores in their polymorphic complexity. Previous approaches to understanding the evolution of polymorphism have been based on analyses of (1) the functional role of polymorphs or (2) presumed evolutionary costs and benefits based on evolutionary theory that postulates polymorphism should be evolutionarily sustainable only in more stable environments because polymorphism commonly leads to the loss of feeding and sexual competence. Here we use bryozoans from opposite shores of the Isthmus of Panama to revisit the environmental hypothesis by comparison of faunas from distinct oceanographic provinces that differ greatly in environmental variability, and we then examine the correlations between the extent of polymorphism in relation to patterns of ecological succession and variation in life histories. We find no support for the environmental hypothesis. Distributions of the incidence of polymorphism in the oceanographically unstable Eastern Pacific are indistinguishable from those in the more stable Caribbean. In contrast, the temporal position of species in a successional sequence is collinear with the degree of polymorphism because species with fewer types of polymorphs are competitively replaced by species with higher numbers of polymorphs on the same substrata. Competitively dominant species also exhibit patterns of growth that increase their competitive ability. The association between degrees of polymorphism and variations in life histories is fundamental to understanding of the macroevolution of polymorphism.

Formation of the Isthmus of Panama.

The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed many millions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways, with formation of the Isthmus of Panama sensu stricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.

Molluscan subfossil assemblages reveal the long-term deterioration of coral reef environments in Caribbean Panama.

Caribbean reef corals have declined sharply since the 1980s, but the lack of prior baseline data has hindered identification of drivers of change. To assess anthropogenic change in reef environments over the past century, we tracked the composition of subfossil assemblages of bivalve and gastropod mollusks excavated from pits below lagoonal and offshore reefs in Bocas del Toro, Panama. The higher prevalence of (a) infaunal suspension-feeding bivalves and herbivorous and omnivorous gastropods in lagoons and (b) epifaunal and suspension-feeding bivalves and carnivorous and suspension-feeding gastropods offshore reflected the greater influence of land-based nutrients/sediments within lagoons. Temporal changes indicated deteriorating environmental conditions pre-1960 in lagoons and post-1960 offshore, with offshore communities becoming more similar to lagoonal ones since 1960. Relative abundances of dominant bivalve species tracked those of their coral hosts, revealing broader ecosystem effects of coral community change. The nature and timing of changes implicate land-based runoff in reef deterioration.

Plasma dihydroceramide species associate with waist circumference in Mexican American families.

OBJECTIVE: Waist circumference (WC), the clinical marker of central obesity, is gaining popularity as a screening tool for type 2 diabetes (T2D). While there is epidemiologic evidence favoring the WC-T2D association, its biological substantiation is generally weak. Our objective was to determine the independent association of plasma lipid repertoire with WC. METHODS: Samples and data from the San Antonio Family Heart Study of 1208 Mexican Americans from 42 extended families were used. Association of plasma lipidomic profiles with the cross-sectionally assessed WC was determined. Plasma lipidomic profiling entailed liquid chromatography with mass spectrometry. Statistical analyses included multivariable polygenic regression models and bivariate trait analyses using the SOLAR software. RESULTS: After adjusting for age and sex interactions, body mass index, homeostasis model of assessment-insulin resistance, total cholesterol, triglycerides, high density lipoproteins and use of lipid lowering drugs, dihydroceramides as a class were associated with WC. Dihydroceramide species 18:0, 20:0, 22:0, and 24:1 were significantly associated and genetically correlated with WC. Two sphingomyelin species (31:1 and 41:1) were also associated with WC. CONCLUSIONS: Plasma dihydroceramide levels independently associate with WC. Thus, high resolution plasma lipidomic studies can provide further credence to the biological underpinnings of the association of WC with T2D.

Plasma lipidomic profile signature of hypertension in Mexican American families: specific role of diacylglycerols.

Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis, and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies, such as plasma lipidomic profiling, promise a better understanding of disorders in which there is a derangement of the lipid metabolism. However, association of plasma lipidomic profiles with hypertension in a high-risk population, such as Mexican Americans, has not been evaluated before. Using the rich data and sample resource from the ongoing San Antonio Family Heart Study, we conducted plasma lipidomic profiling by combining high-performance liquid chromatography with tandem mass spectroscopy to characterize 319 lipid species in 1192 individuals from 42 large and extended Mexican American families. Robust statistical analyses using polygenic regression models, liability threshold models, and bivariate trait analyses implemented in the SOLAR software were conducted after accounting for obesity, insulin resistance, and relative abundance of various lipoprotein fractions. Diacylglycerols, in general, and the DG 16:0/22:5 and DG 16:0/22:6 lipid species, in particular, were significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), as well as liability of incident hypertension measured during 7140.17 person-years of follow-up. Four lipid species, including the DG 16:0/22:5 and DG 16:0/22:6 species, showed significant genetic correlations with the liability of hypertension in bivariate trait analyses. Our results demonstrate the value of plasma lipidomic profiling in the context of hypertension and identify disturbance of diacylglycerol metabolism as an independent biomarker of hypertension.

Variability in associations of phosphatidylcholine molecular species with metabolic syndrome in Mexican-American families.

Plasma lipidomic studies using high performance liquid chromatography and mass spectroscopy offer detailed insights into metabolic processes. Taking the example of the most abundant plasma lipid class (phosphatidylcholines) we used the rich phenotypic and lipidomic data from the ongoing San Antonio Family Heart Study of large extended Mexican-American families to assess the variability of association of the plasma phosphatidylcholine species with metabolic syndrome. Using robust statistical analytical methods, our study made two important observations. First, there was a wide variability in the association of phosphatidylcholine species with risk measures of metabolic syndrome. Phosphatidylcholine 40:7 was associated with a low risk while phosphatidylcholines 32:1 and 38:3 were associated with a high risk of metabolic syndrome. Second, all the odd chain phosphatidylcholines were associated with a reduced risk of metabolic syndrome implying that phosphatidylcholines derived from dairy products might be beneficial against metabolic syndrome. Our results demonstrate the value of lipid species-specific information provided by the upcoming array of lipidomic studies and open potential avenues for prevention and control of metabolic syndrome in high prevalence settings.

Anthropogenic mortality on coral reefs in Caribbean Panama predates coral disease and bleaching.

Caribbean reef corals have declined precipitously since the 1980s due to regional episodes of bleaching, disease and algal overgrowth, but the extent of earlier degradation due to localised historical disturbances such as land clearing and overfishing remains unresolved. We analysed coral and molluscan fossil assemblages from reefs near Bocas del Toro, Panama to construct a timeline of ecological change from the 19th century-present. We report large changes before 1960 in coastal lagoons coincident with extensive deforestation, and after 1960 on offshore reefs. Striking changes include the demise of previously dominant staghorn coral Acropora cervicornis and oyster Dendrostrea frons that lives attached to gorgonians and staghorn corals. Reductions in bivalve size and simplification of gastropod trophic structure further implicate increasing environmental stress on reefs. Our paleoecological data strongly support the hypothesis, from extensive qualitative data, that Caribbean reef degradation predates coral bleaching and disease outbreaks linked to anthropogenic climate change.

Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population.

CONTEXT: Chemerin is a novel adipokine previously associated with metabolic syndrome phenotypes in a small sample of subjects from Mauritius. OBJECTIVE: The aim of the study was to determine whether plasma chemerin levels were associated with metabolic syndrome phenotypes in a larger sample from a second, unrelated human population. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Plasma samples were obtained from the San Antonio Family Heart Study (SAFHS), a large family-based genetic epidemiological study including 1431 Mexican-American individuals. Individuals were randomly sampled without regard to phenotype or disease status. This sample is well-characterized for a variety of phenotypes related to the metabolic syndrome. MAIN OUTCOMES: Plasma chemerin levels were measured by sandwich ELISA. Linear regression and correlation analyses were used to determine associations between plasma chemerin levels and metabolic syndrome phenotypes. RESULTS: Circulating chemerin levels were significantly higher in nondiabetic subjects with body mass index (BMI) greater than 30 kg/m(2) compared with those with a BMI below 25 kg/m(2) (P < 0.0001). Plasma chemerin levels were significantly associated with metabolic syndrome-related parameters, including BMI (P < 0.0001), fasting serum insulin (P < 0.0001), triglycerides (P < 0.0001), and high-density lipoprotein cholesterol (P = 0.00014), independent of age and sex in nondiabetic subjects. CONCLUSION: Circulating chemerin levels were associated with metabolic syndrome phenotypes in a second, unrelated human population. This replicated result using a large human sample suggests that chemerin may be involved in the development of the metabolic syndrome.

Genetics of variation in serum uric acid and cardiovascular risk factors in Mexican Americans.

BACKGROUND: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear. OBJECTIVE: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study. METHODS: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR. RESULTS: Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2. SUMMARY: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors.

Historical decline in coral reef growth after the Panama Canal.

The Panama Canal is near its vessel size and tonnage handling capacity, and Panamanians have decided to expand it. The expansion of the Canal may consider the historical long-lasting impacts on marine coastal habitats particularly on sensitive coral reefs. These potential impacts were discussed during the national referendum as were other equally important issues, such as its effects on forests, watersheds, and water supply. Coral growth rates provide a direct measure of coral fitness and past environmental conditions comparable to analyses of tree rings. We examined stable isotopes, metal geochemical tracers, and growth rates on a century-long (1880-1989) chronology based on 77 cores of the dominant reef-building coral Siderastrea siderea collected near the Caribbean entrance to the canal. Our results showed a gradual decline in coral growth unrelated to changes in sea surface temperature but linked to runoff and sedimentation to coastal areas resulting from the construction and operation of the Panama Canal.

A chromosome 11q quantitative-trait locus influences change of blood-pressure measurements over time in Mexican Americans of the San Antonio Family Heart Study.

Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single-time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP.

Environmental change preceded Caribbean extinction by 2 million years.

Paleontologists typically treat major episodes of extinction as single and distinct events in which a major environmental perturbation results in a synchronous evolutionary response. Alternatively, the causes of biotic change may be multifaceted and extinction may lag behind the changes ultimately responsible because of nonlinear ecological dynamics. We examined these alternatives for the major episode of Caribbean extinction 2 million years ago (Ma). Isolation of the Caribbean from the Eastern Pacific by uplift of the Panamanian Isthmus was associated with synchronous changes in Caribbean near shore environments and community composition between 4.25 and 3.45 Ma. Seasonal fluctuations in Caribbean seawater temperature decreased 3-fold, carbonate deposition increased, and there was a striking, albeit patchy, shift in dominance of benthic ecosystems from heterotrophic mollusks to mixotrophic reef corals and calcareous algae. All of these changes correspond well with a simple model of decreased upwelling and collapse in planktonic productivity associated with the final stages of the closure of the isthmian barrier. However, extinction rates of mollusks and corals did not increase until 3-2 Ma and sharply peaked between 2 and 1 Ma, even though extinction overwhelmingly affected taxa commonly associated with high productivity. This time lag suggests that something other than environmental change per se was involved in extinction that does not occur as a single event. Understanding cause and effect will require more taxonomically refined analysis of the changing abundance and distribution patterns of different ecological guilds in the 2 million years leading up to the relatively sudden peak in extinction.