Dilatation of the cystic duct appears to be rare but was demonstrated in the patient illustrated below. A 36-year-old man was investigated because of upper abdominal symptoms including abdominal pain. Blood tests revealed a minor elevation of bilirubin (1.7 mg/dl, 29 μmol/l) and a mild elevation of alanine aminotransferase and gamma-glutamyl transpeptidase. An ultrasound study showed a dilated bile duct, mild dilatation of intrahepatic ducts and minor thickening of the wall of the gallbladder. MRCP revealed a dilated lower bile duct and marked dilatation of the portion of the cystic duct that entered the bile duct (Figure 1).

Other images showed that the junction of the cystic duct and bile duct was widely patent. Tipifarnib in vitro Figure 2 demonstrates a narrow distal bile duct (short arrow), the main pancreatic duct (long arrows) and a long common channel (thick arrow). As the cyst appeared to spare at least some of the common hepatic duct, it was classified as type IB with atypical involvement of a portion of the cystic LDK378 duct. He was treated by cyst excision, cholecystectomy and Roux-en-Y hepaticojejunostomy to correct the extrahepatic obstruction and to minimize the risk of malignant change within the cyst wall. “
“A national viral hepatitis therapy program was launched in

Taiwan in October 2003. This study aimed to assess the impact of the program on reduction of end-stage liver disease burden. Profiles of national registries of households, cancers and death certificates were used to derive incidence and mortality MCE of end-stage liver diseases from 2000 to 2011. The age-gender-adjusted incidence and mortality rates of hepatocellular carcinoma (HCC) and chronic liver diseases and cirrhosis of adults aged 30-69 years were compared before and after launching the program using Poisson regression models. A total of 157,570 and 61,823 patients (15-25% of the eligible for reimbursed treatment) received therapy for chronic hepatitis B and C, respectively,

by 2011. There were 42,526 chronic liver diseases and cirrhosis deaths, 47,392 HCC deaths, and 74,832 incident HCC cases occurred in 140,814,448 person-years from 2000 to 2011. Male gender and elder age were associated with a significantly increased risk of chronic liver diseases and cirrhosis and HCC. The mortality and incidence rates of the end-stage liver diseases decreased continuously from 2000-2003 (before therapy program) through 2004-2007 to 2008-2011 in all age and gender groups. The age-gender-adjusted rate ratio (95% confidence interval, p-value) in 2008-2011 was 0.78 (0.76-0.80, p<0.001) for chronic liver diseases and cirrhosis mortality, 0.76 (0.75-0.78, p<0.005) for HCC mortality, and 0.86 (0.85-0.88, p<0.

Additionally, medication acceptance rates of baseline adherers on follow up is currently unknown. Aims: 1) To investigate the effects and durability of IBD pharmacist targeted counselling intervention on adherence Selleckchem Lumacaftor rates, necessity and concerns with the primary outcome of increasing medication acceptance. 2) To test whether adherence at baseline changes on long term follow up. Methods: Patients were recruited from the IBD clinic of a Sydney tertiary hospital. Medication Adherence

Rating scale (MARS) questionnaire screened for non-adherence (defined as score ≤16). Beliefs about Medications Questionnaire (BMQ) addressed necessity and concerns (with “medication acceptance” defined as high Necessity >15/ low Concerns score ≤15). Non-adherers were targeted for a structured personalized counselling session with an IBD pharmacist addressing misperceptions, concerns, risk and other queries. Adherers (MARS ≥ 17) were recruited as controls. All patients were followed up with 3-monthly MARS and BMQ questionnaires. Data were analyzed using the Wilcoxon signed rank and Kruskal-Wallis non-parametric statistics and Chi square test. Results: A total of 89 consecutive patients (49% males, median age 37 years, 67% Crohn’s, PS-341 concentration median follow up 12 months, 48% 5-ASA, 66% immunomodulator, 26% biological agent) were prospectively recruited and 21 (23.5%) were non-adherers. For non-adherers, baseline median MARS was 16 increasing

to 19.0 at 3 months (P = 0.02) corresponding to significant increase in medication acceptance rate (P = 0.007). Medication acceptance rates at baseline for non-adherers and adherers were 10.5% and 44.3% respectively (P = 0.008) and at 3 months they were 58.3% and 42.3% respectively (P = 0.358, Table 1). Durability of acceptance was up to 15 months in non-adherers (66.6% P = 0.015) but had declined in baseline adherers

(23.0%, P = 0.095). Non-adherers’ Concern scores significantly decreased from baseline to 3 months (median difference 6, P = 0.033), MCE公司 9 months (median difference 6, P = 0.030) with a durable trend at 15 months (median difference 7, P = 0.08). Although baseline adherers’ median MARS increased from 19 to 20 at 15 months (P = 0.028), 9% had become non-adherent on follow up. Conclusion: Targeted pharmacist counselling intervention on non-adherers effectively increases medication acceptance rates to be equivalent to adherers and was durable to at least 15 months. Medication concerns decreased significantly and were sustained for at least 9 months for non-adherers. However, 9% of adherers became non-adherent at follow up with decreasing medication acceptance rates by 15 months. Medication adherence, therefore, is a dynamic factor that may change over time. Overall, a single targeted session is impactful not only by affecting concerns and adherence in the short term but by initiating a shift in the patient’s attitudes towards their medications. Table 1.

63 Several other medications have been used in the treatment of EoE. Montelukast, a leukotriene inhibitor used in asthma prevention, has been studied in an uncontrolled adult trial but its use was limited because of side effects.72 Mepolizumab, a humanized monoclonal antibody against IL-5, has been shown to effectively reduce esophageal eosinophil counts, but its effect on symptoms was disappointing.73,74 Therefore, given its cost and limited clinical efficacy, Ferroptosis phosphorylation the role of this medication requires further evaluation. As a relatively recently discovered medical condition, EoE is still associated with significant diagnostic, therapeutic and prognostic uncertainties. Controversy

remains as to whether treatment should aim for complete mucosal remission or merely for symptom control. This issue cannot be resolved based on current published knowledge. In this context it will be important to prospectively click here study the natural history of untreated EoE in children and adults. In addition, well-designed head-to-head randomized clinical trials are urgently called for to inform best treatment

guidelines for patients with EoE. Case study 1 A 12-month-old girl (birthweight 3.25 kg) was referred with a history of unsettled behavior, feeding difficulties and failure to thrive. She was breast-fed until 8 months of age, and solids were introduced from 5 months. She initially presented with minor regurgitation after feeds but no overt vomiting. An empirical trial of ranitidine at 2 months of age for suspected GERD did not improve her symptoms. She also had persistent MCE low-grade diarrhea with four to six loose bowel motions daily, but without visible blood. From 4 months of age, her

growth velocity slowed significantly and supplemental soy formula was started by her parents. At the time of first review by a pediatric allergist at 12 months, she was generally well but had ongoing diarrhea. Her weight had fallen to well below the 3rd weight-for-age percentile. On examination, she had a distended abdomen with significant loss of subcutaneous tissue. Bloods tests revealed a mild microcytic anemia. The tissue transglutaminase IgA antibody was negative (normal total serum IgA) while receiving wheat in her diet. SPTs were negative to cow’s milk 0 mm, egg 0 mm, soy 0 mm and wheat 0 mm. The APT was positive for cow’s milk and soy, and negative for egg and wheat. A gastroscopy at the age of 15 months revealed longitudinal furrowing and white plaques in the esophagus; stomach and duodenum were macroscopically normal. Histological examination of esophageal biopsies was in keeping with a diagnosis of EoE, with 42 eosinophils/HPF in the upper, 38/HPF in the middle and 28/HPF in the lower esophagus. Basal cell proliferation occupying more than 50% of the epithelial thickness was demonstrated. Biopsies from stomach and duodenum were normal, thus excluding celiac disease.

αGalCer, alpha-galactosylceramide; α-SMA, alpha-smooth muscle actin; ctgf, connective tissue growth factor; FACS, fluorescent activated cell sorting; FFPE, formalin-fixed paraffin-embedded;

Foxf1, Forkhead box F1; Gli, glioblastoma; Hh, Hedgehog; HSC, hepatic stellate cells; iNKT, invariant natural killer T; LMNC, liver mononuclear cell; MCD, selleck chemicals methionine choline deficient; mmp9, matrix metalloproteinase 9; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NK, natural killer; NKT, natural killer T; Ptc+/−, patched; Shh, sonic hedgehog; Tgf-β, transforming growth factor beta; Vcam1, vascular cell adhesion molecule 1. C57BL/6 wildtype (WT) (Jackson Laboratories, Bar Harbor, ME), Patched-deficient (Ptc+/−) mice (from R.J. Wechsler-Reya, Duke University, NC), and CD1d-deficient mice (from Z.P. Li, Johns Hopkins University, Baltimore, MD) were fed a methionine-choline deficient (MCD) diet or control chow for 8 weeks. Ptc+/−

mice have only one copy of patched, a Hedgehog (Hh)-pathway repressor. Therefore, they are unable to silence Hh-signaling and exhibit excessive Hh-pathway activity.25 NKT cells are genetically absent in CD1d-deficient mice.26 Formalin-fixed paraffin-embedded (FFPE)-livers were analyzed27 (for detailed protocol and antibodies, see Supporting Information Materials and Methods). Total liver RNA extraction

and messenger RNA (mRNA) quantification by real-time qualitative reverse-transcription polymerase chain reaction (qRT-PCR) were performed as detailed in Supporting Information Angiogenesis inhibitor Materials and Methods.27 Primers are in Supporting Information Table 1. Hydroxylproline content in whole liver specimens was quantified colorimetrically.27 LMNC were isolated from WT mice28, 29 medchemexpress and characterized by fluorescent antibody cell sorting (FACS) as detailed in Supporting Information Materials and Methods. LMNC were cultured in complete NKT media (RPMI 1640, supplemented with IL2 [10 ng/mL; Biolegend] and 10% heat-inactivated fetal bovine serum),28 with or without the NKT cell ligand, alpha-galactosylceramide (αGalCer; 100 ng/mL; Axxora, Cat. no. 306027, CA), for 24 hours. This αGalCer dose elicits maximal iNKT activation.30 Conditioned media were then added to primary murine HSCs for 1 day and RNA was harvested for qRT-PCR. Experiments were performed in duplicate wells and repeated twice. Murine cholangiocyte 603B line (from Yoshiyuki Ueno, Tohoku University, Sendai, Japan, and G. Gores, Mayo Clinic, Rochester, MN),31 rat HSC line 8B (from M. Rojkind, George Washington University, Washington, DC),32 and murine invariant hybridoma cell line DN32 (from Albert Bendelac, University of Chicago, Chicago, IL)33 were cultured according to established protocols.

5, 17 All data used in these analyses were obtained within 6 months of liver biopsy. The following variables were analyzed: demographic features (e.g., age at enrollment [years], gender, race [white or other], and ethnicity [Hispanic/Latino]); family history, clinical INCB024360 data (e.g., waist circumference, body mass index [BMI] (kg/m2), diastolic blood pressure [BP], and systolic BP); laboratory measures (e.g., triglyceride [Tg], high-density lipoprotein [HDL], and fasting serum glucose levels); and presence of diabetes. Diabetes status was

based upon previous history of diabetes according to patient/physician report (and/or use of medications to treat diabetes and/or fasting plasma glucose >125 mg/dL or a 2-hour glucose >200 mg/dL during an oral glucose tolerance test during the baseline visit). To determine whether the association between family history of diabetes and advanced histology in NAFLD is

mediated by prediabetes, the cohort was further classified into prediabetic and normoglycemic participants. Prediabetes was defined as fasting glucose between 100 and 125 mg/dL or glycated hemoglobin (hemoglobin A1c; HbA1c) between 5.7% and 6.4%; normoglycemia was defined as fasting glucose <100 mg/dL and HbA1c <5.7%. Patients with discordant results (e.g., glucose <100 mg/dL and HbA1c >6.4% or patients without diagnosis of diabetes, but with discordant one-time laboratory values) were set to missing (N = 22). Family history of a condition or disease was self-reported to be present in a first-degree medchemexpress relative selleck products (i.e., parent, sibling, or child). The presence of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 G allele was determined for each

patient, as previously described,18 and included in the analysis. Liver biopsy slides stained with hematoxylin and eosin and Masson’s trichrome were reviewed and scored centrally by the NASH CRN pathology committee, as previously reported.19 Central pathology committee pathologists reviewed biopsies without any knowledge of the local pathology readings or clinical or laboratory values of patients in the study.19, 20 Fibrosis was graded based on Brunt’s modified classification: 0 = no fibrosis; 1a = mild, zone 3 perisinusoidal fibrosis (requires trichrome); 1b = moderate, zone 3 perisinusoidal fibrosis (does not require trichrome); 1c = portal/periportal fibrosis; 2 = zone 3 perisinusoidal or periportal fibrosis or both; 3 = bridging fibrosis; and 4 = cirrhosis.19-22 Advanced fibrosis was defined as stages 3 and 4 and compared with mild or no fibrosis (stages 0-2). Any fibrosis was defined as stages 1-4 and compared with no fibrosis (stage 0). Diagnosis of NASH was classified as either definite NASH or suspicious for NASH (i.e., borderline NASH) based upon central pathology reading, as previously defined,19, 20 and compared with no NASH. These categories were defined before conducting statistical analyses.

“
“Summary.  In this study,

we describe a flow cytometry (FC) system for detecting antibodies to factor VIII (FVIII) and compare its results with those of enzyme-linked immunosorbent assay (ELISA) that detects both inhibitory (I-Ab) and non-inhibitory (NI-Ab) antibodies and the Nijmegen modification of the Bethesda method, detecting I-Ab. FC was set up in our laboratory. Recombinant FVIII (rFVIII) was coupled to microspheres (FVIII-m) and reacted with different plasma dilutions. Microspheres without rFVIII were used as control (control-m). Captured anti-FVIII antibodies were detected using anti-human IgG. Plasma samples BVD-523 clinical trial from the following patients with severe haemophilia A (SHA) patients were evaluated: 17 P (patients without I-Ab, <0.5 BU mL−1); 13 PI (patients with I-Ab, 1.1–8200 BU mL−1). Of these 13, two PI were referred during immune tolerance induction (ITI), and plasmas from 12 healthy donors (HD) were evaluated. Semiquantitative results were given as an index

(the highest mean fluorescence intensity ratio between FVIII-m and control-m multiplied by the inverse of the corresponding plasma dilution). Both plasma and serum were suitable for the test. FC agreed with the Bethesda method (r = 0.8; P = 0.0001). FC and ELISA had 80% of coincidence. Four of 17 patients (23.5%) had NI-Ab by FC, and two of them developed high levels of I-Ab later on. This test provides a useful alternative for measuring FVIII antibodies Epigenetics Compound Library solubility dmso supplementing Bethesda assay. FC is fast and easy to perform. No more than 200 μL of plasma or serum is required especially making it useful for paediatric patients. “
“Summary.  Inhibitor development remains a challenge to appropriate haemophilia treatment. This challenge is being addressed, in part, by an expanding knowledge of the

mechanisms that drive inhibitor development including how elements of the innate immune response play a role in inhibitor development. There are promising therapies that may suppress an active immune response. Models to assess the immune responses are becoming ever more sophisticated. Newer models 上海皓元医药股份有限公司 can be used at the preclinical level to evaluate the role of MHC-class II presentation of antigens in both in vitro cell culture studies and in vivo in transgenic mice that express either the protein to be studied or that express human MHC-class II proteins. Parallel to work designed to reduce or reverse inhibitors is development of improved therapies including bypassing agents to treat patients with inhibitors. With these new treatment modalities comes the problem of assessing efficacy at the preclinical level. Models to evaluate bleeding are being developed that may give a more subtle assessment of bypassing agents. These models represent in part an attempt to incorporate the role of ongoing bleeding into the evaluation.

“
“Summary.  In this study,

we describe a flow cytometry (FC) system for detecting antibodies to factor VIII (FVIII) and compare its results with those of enzyme-linked immunosorbent assay (ELISA) that detects both inhibitory (I-Ab) and non-inhibitory (NI-Ab) antibodies and the Nijmegen modification of the Bethesda method, detecting I-Ab. FC was set up in our laboratory. Recombinant FVIII (rFVIII) was coupled to microspheres (FVIII-m) and reacted with different plasma dilutions. Microspheres without rFVIII were used as control (control-m). Captured anti-FVIII antibodies were detected using anti-human IgG. Plasma samples this website from the following patients with severe haemophilia A (SHA) patients were evaluated: 17 P (patients without I-Ab, <0.5 BU mL−1); 13 PI (patients with I-Ab, 1.1–8200 BU mL−1). Of these 13, two PI were referred during immune tolerance induction (ITI), and plasmas from 12 healthy donors (HD) were evaluated. Semiquantitative results were given as an index

(the highest mean fluorescence intensity ratio between FVIII-m and control-m multiplied by the inverse of the corresponding plasma dilution). Both plasma and serum were suitable for the test. FC agreed with the Bethesda method (r = 0.8; P = 0.0001). FC and ELISA had 80% of coincidence. Four of 17 patients (23.5%) had NI-Ab by FC, and two of them developed high levels of I-Ab later on. This test provides a useful alternative for measuring FVIII antibodies Abiraterone research buy supplementing Bethesda assay. FC is fast and easy to perform. No more than 200 μL of plasma or serum is required especially making it useful for paediatric patients. “
“Summary.  Inhibitor development remains a challenge to appropriate haemophilia treatment. This challenge is being addressed, in part, by an expanding knowledge of the

mechanisms that drive inhibitor development including how elements of the innate immune response play a role in inhibitor development. There are promising therapies that may suppress an active immune response. Models to assess the immune responses are becoming ever more sophisticated. Newer models medchemexpress can be used at the preclinical level to evaluate the role of MHC-class II presentation of antigens in both in vitro cell culture studies and in vivo in transgenic mice that express either the protein to be studied or that express human MHC-class II proteins. Parallel to work designed to reduce or reverse inhibitors is development of improved therapies including bypassing agents to treat patients with inhibitors. With these new treatment modalities comes the problem of assessing efficacy at the preclinical level. Models to evaluate bleeding are being developed that may give a more subtle assessment of bypassing agents. These models represent in part an attempt to incorporate the role of ongoing bleeding into the evaluation.

Evidence for three nonindigenous Ulva species in temperate Australia is discussed. “
“Although type IV pilus has been implicated in the phototactic motility of some unicellular cyanobacteria, its regulatory mechanism and the effect of environmental factors on motility are still unknown. Lenvatinib mw Equally important is the ability of cyanobacterial cells to anchor themselves to an environment that is conducive for survival. We compared the motility of a newly isolated unicellular brackish cyanobacterium, Synechocystis sp.

UNIWG, with the morphologically and phylogenetically similar freshwater cyanobacterium Synechocystis sp. PCC6803 under different environmental conditions. The phototactic motility of Synechocystis sp. UNIWG on semisolid BG-11 medium with various concentrations of nitrogen source was significantly faster than that of Synechocystis PCC6803. Interestingly, the cell surface of Synechocystis sp. UNIWG showed the presence of rigid spicules when grown in liquid BG-11, a phenomenon that was absent in Synechocystis PCC6803. Negative staining of Synechocystis sp. this website UNIWG revealed the presence of two distinct pilus morphotypes, which resembled type IV pili and thin pili of Synechocystis PCC6803. This finding suggested a similar pattern of phototactic motility

in both strains. However, the rigid spicules on Synechocystis sp. UNIWG seem to be more of a hindrance during type IV motility. It was determined that the spicules were degraded when the cells moved, such as under prolonged darkness and/or depletion of nitrogen source, indicating that the function of the spicules is to attach the cell to an environment that is conducive for its survival. Thus, Synechocystis sp. UNIWG shows phototaxis regulation that is more complex than Synechocystis MCE PCC6803. “
“Many microalgae release polysaccharides, but the effects of the polysaccharides

on mutual flocculation of microalgae and clay in aquatic environments have not been well studied. Aphanothece halophytica Frémy is a bloom-forming cyanobacterium in salterns and can release large amounts of polysaccharide (AH-RPS). In the present study, we investigated the effect of AH-RPS on mutual flocculation of cyanobacterium and clay and further explored the mechanisms by which AH-RPS affected mutual flocculation. We determined that AH-RPS possessed clay-dispersing activity as defined as the ability to inhibit the flocculation and sedimentation of clay suspensions in water. Supplementation of AH-RPS in cyanobacterial cell suspensions and in the culture media containing the same kaolin clay concentration dose dependently decreased flocculation of cyanobacterial cells and increased clay-dispersing activity. These findings indicate that the clay-dispersing activity of AH-RPS was related to its inhibitory effect on mutual flocculation of cyanobacterial cells and clay particles.

Bates, with their more important and characteristic differences; thus within the same natural section of the genus Onthophagus, there are species which have either a single cephalic horn, or two distinct horns. Emlen et al. (2005) have recently verified Bates’ observations using a phylogeny of 48 species of Onthophagus; Emlen counted at least 25 gains and losses of horns within this clade, with no indication of any directional trend in horn

morphology. There BMN 673 price is little question that, when present, these horns have an adaptive function, allowing males to increase their fitness by increasing their number of matings, so the lack of directional change likely results from the gains and losses occurring too rapidly for any directional change to be evident. Horn losses appear to be causally linked to changes to ecological variables such as population density or sex ratios favouring hornless males (Moczek, 2003; Pomfret & Knell, 2008). Studies of introduced populations of horned beetles have shown measurable changes in horn size and frequency after <40 years, apparently linked to densities of the introduced populations selleck (Moczek, 2003). Although exaggerated

structures in dinosaurs (e.g. horns, frills, crests and domes) would have evolved more slowly than beetle horns due to longer generation times, it 上海皓元医药股份有限公司 is nonetheless possible that they showed a similar amount of evolutionary lability, particularly over macroevolutionary timescales. If so, especially given the relatively low temporal resolution characteristic of the Mesozoic vertebrate record, we should not be surprised to find a lack of evidence for directional morphological change in exaggerated characters evolving under sexual selection. The second test of the species recognition hypothesis proposed by Padian & Horner is that species with exaggerated traits should occur in sympatry with others bearing similar features at some point during the evolution of these

traits. This contention is founded on the idea that traits used in species recognition should be more divergent when species occur in sympatry. Thus, the songs of closely related sympatric pairs of antbird (Thamnophilidae) differ from each other more than the songs of closely related allopatric pairs (Seddon, 2005). Similarly, island-dwelling species of wildfowl (Anseriformes) that live in sympatry with few congeners are than less brightly coloured than anseriforms sharing the same habitat with more congeners (Figuerola & Green, 2000). This prediction has several problems as applied to Mesozoic dinosaurs. The first is that the proposed correlation does not seem to be universal among extant animals, weakening any inferences based upon the fossil record.

Bates, with their more important and characteristic differences; thus within the same natural section of the genus Onthophagus, there are species which have either a single cephalic horn, or two distinct horns. Emlen et al. (2005) have recently verified Bates’ observations using a phylogeny of 48 species of Onthophagus; Emlen counted at least 25 gains and losses of horns within this clade, with no indication of any directional trend in horn

morphology. There Palbociclib nmr is little question that, when present, these horns have an adaptive function, allowing males to increase their fitness by increasing their number of matings, so the lack of directional change likely results from the gains and losses occurring too rapidly for any directional change to be evident. Horn losses appear to be causally linked to changes to ecological variables such as population density or sex ratios favouring hornless males (Moczek, 2003; Pomfret & Knell, 2008). Studies of introduced populations of horned beetles have shown measurable changes in horn size and frequency after <40 years, apparently linked to densities of the introduced populations find more (Moczek, 2003). Although exaggerated

structures in dinosaurs (e.g. horns, frills, crests and domes) would have evolved more slowly than beetle horns due to longer generation times, it 上海皓元医药股份有限公司 is nonetheless possible that they showed a similar amount of evolutionary lability, particularly over macroevolutionary timescales. If so, especially given the relatively low temporal resolution characteristic of the Mesozoic vertebrate record, we should not be surprised to find a lack of evidence for directional morphological change in exaggerated characters evolving under sexual selection. The second test of the species recognition hypothesis proposed by Padian & Horner is that species with exaggerated traits should occur in sympatry with others bearing similar features at some point during the evolution of these

traits. This contention is founded on the idea that traits used in species recognition should be more divergent when species occur in sympatry. Thus, the songs of closely related sympatric pairs of antbird (Thamnophilidae) differ from each other more than the songs of closely related allopatric pairs (Seddon, 2005). Similarly, island-dwelling species of wildfowl (Anseriformes) that live in sympatry with few congeners are than less brightly coloured than anseriforms sharing the same habitat with more congeners (Figuerola & Green, 2000). This prediction has several problems as applied to Mesozoic dinosaurs. The first is that the proposed correlation does not seem to be universal among extant animals, weakening any inferences based upon the fossil record.