For approved compounds, combination of AL-335 with the NS3/4A pro

For approved compounds, combination of AL-335 with the NS3/4A protease inhibitor, learn more simeprevir, exhibited the greatest synergy with a synergy volume of 97.2 μM2%. AL-335 also exhibited synergistic interactions with the investigational HCV NS5A inhibitor, daclatasvir, (38.0 μM2%) and the investiga-tional non-nucleoside polymerase inhibitor, setrobuvir, (29.5 μM2%) whereas the interaction with ribavirin

was additive (6.8 μM2%). Conclusions: Future IFN-free therapy for CHC will require a combination of compounds with different mechanisms of action. AL-335 demonstrates an in vitro antiviral profile that suggests it may become an important component of IFN-free combination therapy. To this end, AL-335 is currently advancing towards human clinical trials for CHC. Disclosures: Kenneth Shaw – Employment: ABT-737 clinical trial Alios Biopharma Guangyi Wang – Employment: Alios Biopharma, Inc. David B. Smith – Employment: Alios BioPharma Lawrence M. Blatt – Management Position: Alios BioPharma Julian A. Symons – Employment: Alios BioPharma

The following people have nothing to disclose: Hua Tan, Natalia Dyatkina, Leo Beigelman Background: MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus (HCV). Binding of miR-122 to HCV protects the HCV genome from degradation and prevents induction of an innate immune response against the virus. Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels. The aim of this study was to quantify plasma levels of miR-122 at baseline and during miravirsen treatment in HCV patients. Methods: We included 16

out of 36 chronic hepatitis C (genotype 1) patients who received five injections of either 3 mg/kg (n=4), selleck products 5 mg/ kg (n=4), 7 mg/kg (n=4) miravirsen or placebo (n=4) over a 4 week-period in a prior phase 2a study, from whom blood samples were collected at baseline, week 1, week 4, week 6 and week 10/12. RNA was isolated from plasma with the miRCURY RNA isolation kit (Exiqon) and cDNA was synthesized using qScript microRNA cDNA Synthesis Kit (Quanta). The expression levels of miR-122 were measured by quantitative PCR and normalized for levels of miR-93 and miR-191. Results: The median plasma level of miR-122 at baseline in patients receiving miravirsen was 4.3×10^3 compared to 2.2 ×10^3 copies/nl in placebo treated patients (p=ns). During anti-miR treatment, miR-122 levels showed an average 3.7fold reduction (log 2 copies/^l) between baseline and week 1 (p=0.04), 4.5-fold reduction at week 4 (p=0.007), 7-fold reduction at week 6 (p=0.016) and 6-fold reduction at week 10/12 (p=0.006) (Figure 1).

Titration of OCA based on therapeutic response and tolerability m

Titration of OCA based on therapeutic response and tolerability mitigated pruritus while maintaining efficacy. Disclosures: Christopher

L. Bowlus – Advisory Committees or Review Panels: Gilead Sciences, Inc; Consulting: Takeda; Nutlin-3 nmr Grant/Research Support: Gilead Sciences, Inc, Intercept Pharmaceuticals, Bristol Meyers Squibb, Lumena; Speaking and Teaching: Gilead Sciences, Inc Paul J. Pockros – Advisory Committees or Review Panels: Janssen, Merck, Genentech, BMS, Gilead, Boehinger Ingelheim, AbbVioe; Consulting: Genentech, Lumena, Regulus, Beckman Coulter, RMS; Grant/Research Support: Novartis, Intercept, Janssen, Genentech, BMS, Gilead, Vertex, Boehinger Ingelheim, Lumena, Beckman Coulter, AbbVie, RMS, Novartis, Merck; Speaking and Teaching: Genentech, BMS, Gilead Karel J. van Erpecum – Advisory Committees or Review Panels: Bristol Meyers Squibb, Abbvie Mitchell L. Shiffman – Advisory Committees or Review Panels: Merck, Gilead, Boehringer-Ingelheim, Bristol-Myers-Squibb, Abbvie, Janssen; Consulting: Roche/ Genentech, Gen-Probe; Grant/Research Support: Merck, Gilead, Boehringer-Ingelheim, Bristol-Myers-Squibb, GSK, Abbvie, Beckman-Coulter, Achillion, Lumena, Intercept, Novarit, Gen-Probe; Speaking and Teaching: Roche/Genentech, Merck, Gilead, GSK, Janssen, Bayer Frederik Nevens – Consulting: CAF, Intercept, Gore, BMS, Abbvie, Novartis, MSD, Small molecule library Eumedica, Janssen; Grant/Research

Support: Ipsen, Roche, MSD, Astellas Richard Pencek – Employment: Intercept Pharmaceuticals; Stock Shareholder: Intercept Pharmaceuticals Roya Hooshmand-Rad – Employment: Intercept pharmaceuticals Inc. David Shapiro – Employment: Inttercept Pharmaceuticals The following people have nothing to disclose: Joost Drenth, Annarosa Floreani, Catherine Vincent, Velimir A. Luketic, Victor Vargas Background: Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive biliary disease developing in a subgroup of patients during intensive care treatment. click here It is characterized by biliary casts/obliteration, formation of strictures and destruction

of intrahepatic bile ducts consecutively leading to liver cirrhosis and liver failure. Aim of the study was to characterize clinical course, outcome and prognostic features of patients with SC-CIP. Patients and Methods: 49 patients (34 male, age: 46.0+14.2, (mean+SD, years)) with SC-CIP, diagnosed by endoscopic retrograde cholangiography (ERC) were retrospectively analyzed. No patient had evidence of preexisting hepato-biliary disease or inflammatory bowel disease. Histological evaluation of liver biopsies, ICU and endoscopic treatment as well as outcome were evaluated. Results: Respiratory failure (N=11), severe polytrauma (N=9), sepsis (N=7), lung transplantation (N=5), surgery (N=5), cardiopulmonary rescuscitation (N=4) and burn injuries (N=3), were the most common reasons for hospitalization.

If the

If the Vorinostat nmr lesion appears to be an HA, serial follow-up would be indicated. “
“Background and Aims:  A single nucleotide polymorphism near the interleukin-28B (IL28B) gene has been shown to predict hepatitis

C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients. Methods:  A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed. Results:  The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non-responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor

homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV find more genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non-response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non-response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively. Conclusions:  The IL28B genotype may help identify non-responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non-response, the IL28B polymorphism may play a smaller role in Asian patients. “
“Epidemiology of Helicobacter pylori infection has regional variation. Effect of eradication of H. pylori on symptoms of functional dyspepsia is uncertain, and the data in Asian scenario are scanty. The study aimed to see H. pylori positivity rate in patients

of functional dyspepsia and the effect of its eradication on symptoms. Randomized, double-blind, placebo-controlled study was the study design used. Patients of functional dyspepsia defined as per Rome 2 criteria were tested for H. pylori infection by rapid urease test and gastric biopsy. H. pylori-positive patients were randomly allocated to triple therapy (20 mg of omeprazole, check details 500 mg of clarithromycin, and 1000 mg of amoxicillin orally two times daily) and omeperazole plus identical placebo for 2 weeks. Symptoms were assessed with the weekly Likert scale. H. pylori positivity rate in functional dyspepsia was 1160/2000 (58%). At 6 weeks, the eradication rate for H. pylori in triple therapy and placebo group was (181/259 [69.8%] and 13/260 [5.0%], P = 0.001), respectively. On intention-to-treat analysis, the symptom resolution at 1 month was (157/259 [60.7%] and 136/260 [52.3%], P = 0.38), respectively. At 12 months, H. pylori eradication and healing of gastritis in triple therapy and placebo group were (116/174 [66.7%] and 12/180 [6.7%], P = 0.001) and (132/174 [75.9%] and 11/180 [6.1%], P = 0.001), respectively.

5% hydrogenated coconut oil; 10KJ%, 397% fructose; 2% (w/w) chol

5% hydrogenated coconut oil; 10KJ%, 39.7% fructose; 2% (w/w) cholesterol), plus fructose-sucrose in drinking water (12.6%: 55:45) for 30 weeks. At sacrifice, parameters of insulin resistance (IR) and liver function, intrahepatic lipid accumulation, inflammation, fibrosis, oxidative stress, and transcript levels related to fat metabolism, fibrogenesis, fibrolysis, inflammation,

and mac-rophage polarization, as well as proinflammatory cytokines in adipose tissue were analyzed by IHC and quantitative RT-PCR. Results: Mice on the NSD developed a significant increase in body weight, fat deposition, selleck compound IR, liver weight, hepatic ste-atosis, hepatocyte ballooning, and inflammation (NAS score, 4), serum parameters of liver injury, and the level of fibrosis (Ishak score, 3). Their livers showed a significant

upregulation of transcripts related to fibrosis and fibrogenesis (procollagen α1(I), α-SMA, TGFβ1, integrin β6, PDGFRβ, PAI-1, osteopontin, TIMP-1, MMP-2), inflammation (TNFα), M1 macrophage polarization (CCL5), fibrolysis (MMP-8 and MMP-13) and a significant upregulation of genes related to M2 macrophage polarization (MCP-1). Several transcripts related to fat metabolism were also significantly elevated (PPARγ and LPL). The visceral fat of NSD mice displayed a significant upregulation of IL-6 and TNFα expression. In livers, a high IHC expression of oxidative stress related 4-hydroxynonenal and the M2 related YM-1 was found. Conclusion: In this study, we describe the Proteases inhibitor pattern of proinflammatory cytokine/chemokine expression in fat and liver tissue from a novel diet-induced NASH model. This model appears to mimic major aspects of severe human NASH, including

an unfavourable polarization and inflammatory activation of liver and visceral adipose tissue macrophages. Disclosures: Detlef Schuppan – Consulting: Boehringer Ingelheim, Aegerion, Gilead, Gen-zyme, GSK, Pfizer, Takeda, Sanofi Aventis, Silence The following people have nothing to disclose: Yong Ook Kim, Rambabu Surabattula, Kyoung-Sook Park, Shih-yen Weng Background: Currently, the therapeutic selleck products armamentarium to treat Non-alcoholic steatohepatitis (NASH) is limited. Aldosterone plays a role in hepatic fibrogenesis and its modulation could be beneficial for NASH. Aim: To investigate whether eplere-none, a mineralocorticoid receptor antagonist, modulate liver damage in experimental NASH. Methods: C57bl6 mice were fed a choline-deficient amino acid–defined (CDAA) diet for 22 weeks with or without eplerenone supplementation. Serum levels of aminotransferases and aldosterone were measured and hepatic steatosis, inflammation, and fibrosis scored histologi-cally.

5% hydrogenated coconut oil; 10KJ%, 397% fructose; 2% (w/w) chol

5% hydrogenated coconut oil; 10KJ%, 39.7% fructose; 2% (w/w) cholesterol), plus fructose-sucrose in drinking water (12.6%: 55:45) for 30 weeks. At sacrifice, parameters of insulin resistance (IR) and liver function, intrahepatic lipid accumulation, inflammation, fibrosis, oxidative stress, and transcript levels related to fat metabolism, fibrogenesis, fibrolysis, inflammation,

and mac-rophage polarization, as well as proinflammatory cytokines in adipose tissue were analyzed by IHC and quantitative RT-PCR. Results: Mice on the NSD developed a significant increase in body weight, fat deposition, GSK1120212 solubility dmso IR, liver weight, hepatic ste-atosis, hepatocyte ballooning, and inflammation (NAS score, 4), serum parameters of liver injury, and the level of fibrosis (Ishak score, 3). Their livers showed a significant

upregulation of transcripts related to fibrosis and fibrogenesis (procollagen α1(I), α-SMA, TGFβ1, integrin β6, PDGFRβ, PAI-1, osteopontin, TIMP-1, MMP-2), inflammation (TNFα), M1 macrophage polarization (CCL5), fibrolysis (MMP-8 and MMP-13) and a significant upregulation of genes related to M2 macrophage polarization (MCP-1). Several transcripts related to fat metabolism were also significantly elevated (PPARγ and LPL). The visceral fat of NSD mice displayed a significant upregulation of IL-6 and TNFα expression. In livers, a high IHC expression of oxidative stress related 4-hydroxynonenal and the M2 related YM-1 was found. Conclusion: In this study, we describe the MLN8237 cell line pattern of proinflammatory cytokine/chemokine expression in fat and liver tissue from a novel diet-induced NASH model. This model appears to mimic major aspects of severe human NASH, including

an unfavourable polarization and inflammatory activation of liver and visceral adipose tissue macrophages. Disclosures: Detlef Schuppan – Consulting: Boehringer Ingelheim, Aegerion, Gilead, Gen-zyme, GSK, Pfizer, Takeda, Sanofi Aventis, Silence The following people have nothing to disclose: Yong Ook Kim, Rambabu Surabattula, Kyoung-Sook Park, Shih-yen Weng Background: Currently, the therapeutic selleck chemicals llc armamentarium to treat Non-alcoholic steatohepatitis (NASH) is limited. Aldosterone plays a role in hepatic fibrogenesis and its modulation could be beneficial for NASH. Aim: To investigate whether eplere-none, a mineralocorticoid receptor antagonist, modulate liver damage in experimental NASH. Methods: C57bl6 mice were fed a choline-deficient amino acid–defined (CDAA) diet for 22 weeks with or without eplerenone supplementation. Serum levels of aminotransferases and aldosterone were measured and hepatic steatosis, inflammation, and fibrosis scored histologi-cally.

In Soay sheep, where some females are horned while others are hor

In Soay sheep, where some females are horned while others are hornless (‘polled’), horned females are more likely to initiate and win aggressive interactions than polled RXDX-106 order ones (Robinson & Kruuk, 2007) while studies of cattle show that the experimental removal of horns leads to reductions in the ability of individuals to dominate competitors in newly established groups (Boussou, 1972). Comparative studies show that the distribution of female horns and antlers in ruminants is associated with variation

in female group size (Roberts, 1996) although other factors such as the need for effective defence against predators may also be involved. In some mammals where female competition is unusually intense, females often show physiological, morphological and behavioural adaptations that increase their competitive abilities (Clutton-Brock et al., 2006) as they do in a wide range of other animals (West-Eberhard, 1983, 1984; Tobias, Montgomerie & Lyon, 2012). For example, in spotted hyenas, where females compete intensely to raise offspring, well-defined female hierarchies are associated with high levels of reproductive skew and dominant females show elevated testosterone levels, large body size and social

dominance over males (Goymann, East & Hofer, 2001, East & Hofer, 2002, 2010; Holekamp & Dloniak, 2009). Many of the same traits are found in social lemurs and are thought to be associated with intense competition between breeding females for resources Metformin purchase in a fluctuating and unpredictable environment (Jolly, 1984; Wright, 1999; Dunham, 2008). As would be expected, as a result of high levels of reproductive skew, traits likely to affect competitive ability are also unusually well developed in females of some singular cooperative breeders. For example, in meerkats and naked mole rats, females that acquire the breeding position show increased levels of circulating selleck inhibitor testosterone (Faulkes & Abbott, 1997; Clutton-Brock et al., 2006) as

well as a period of secondary growth that is reduced or absent in males and may help them to maintain their status and reproductive output (O’Riain & Braude, 2001; Russell et al., 2004; Clutton-Brock et al., 2006). Breeding females are commonly the largest individuals in their group and are socially dominant to all group members (Reeve & Sherman, 1991; Faulkes & Abbott, 1997; Clutton-Brock et al., 1998b, 2001b). Studies of domestic cattle provide additional evidence that selection in female competitiveness can lead to increased levels of aggression in females and enhanced testosterone levels. In some parts of Switzerland, domestic cattle are forced to fight with each other in tournaments before they are moved up in the summer pastures and their owners bet on their performance.

The special dinner lecture focused on detecting inhibitors in VWD

The special dinner lecture focused on detecting inhibitors in VWD, a difficult

area. Finally, we reviewed the topic of women with VWD and controversies in diagnosis and management, and we learnt the importance of a multidisciplinary approach to the care of these patients. We are considering continuing with the Åland islands meetings as a platform to enhance science and collaboration between experts. Writing support was provided by Ros Kenn, freelance medical editor/writer, and funded by Octapharma. Prof. Dr Erik Berntorp (corresponding author) has received speaker honoraria and research support from Octapharma and participated in Advisory boards. Dr Birte Fuchs is an employee of Octapharma, Germany. Dr Mike Makris has acted as a consultant for CSL Behring and selleck chemical Octapharma. He is the coordinator of the EUHASS project which has received funding from Bayer, Baxter, Biotest, CSL Behring, Grifols, LFB, NovoNordisk, Octapharma and see more Pfizer. Dr Makris is not an employee of any pharmaceutical company, does not own stocks or shares in any and does not own any patents. Prof. Dr Robert Montgomery has received

consultancy fees from GTI Diagnostics/Gen-Probe/Hologics, Baxter, Biogen/IDEC, Bayer, Octapharma and CSL Behring. Asst Prof. Dr Veronica Flood has no conflicts of interest to declare. Prof. James S. O’Donnell has served on the speaker’s bureau for Baxter, Bayer, Novo Nordisk, Leo Pharma and Octapharma. He has also served on the advisory boards of Baxter,

Bayer, Octapharma and Pfizer. He has also received research grant funding awards from Baxter, Bayer and Novo Nordisk. Prof. Dr Augusto B. Federici has received consulting fees (e.g., advisory check details boards) from: Baxter Healthcare, CSL Behring, Grifols, Laboratoires Français de Fractionnement et des Biotechnologies (LFB) and Octapharma. Prof. Dr David Lillicrap has received research funding from Bayer, Baxter, CSL and Biogen-Idec. Dr Paula James has received research funding from CSL Behring, and honoraria from CSL Behring, Baxter and Bayer. Prof. Ulrich Budde has no conflicts of interest to declare. Dr Massimo Morfini has acted as a paid consultant to Bayer, Baxter, Novo Nordisk, Pfizer Advisory Boards and received a fee as invited speaker from Bayer, Novo Nordisk, CSL Behring Symposia and Octapharma. Dr Pia Petrini has no conflicts of interest to declare. Dr Steve Austin has received travel grants from Octapharma, Baxter and Pfizer and speakers’ grants from Octapharma and Bayer. He has been on advisory boards for Baxter and Pfizer. Dr Christoph Kannicht is an employee of Octapharma, Germany. Dr Victor Jiménez-Yuste has received fees for speaking from Octapharma, Grifols, NovoNordisk, Pfizer and has participated in advisory boards sponsored by Grifols, Bayer, NovoNordisk, CSL Behring and Pfizer. Prof.

Thus, it is instructive

to contrast the pathophysiologica

Thus, it is instructive

to contrast the pathophysiological features of biliary atresia with the normal programmed loss of entire biliary apparatus in sea lamprey larvae. Biliary atresia in human infants is characterized by the complete obstruction of bile flow as a result of the destruction or absence of all or a portion of the extrahepatic bile ducts.2–4 As this website part of the underlying disease process or as a result of biliary obstruction, concomitant injury and fibrosis of the intrahepatic bile ducts also occurs to a variable extent. The disorder occurs in 1 in 10,000 to 15,000 live births in the United States, and accounts for approximately one-third of cases of neonatal cholestatic jaundice. It is the most frequent cause of death from liver disease and accounts for about 50% of all liver transplants in children. There is some evidence for two forms of biliary atresia, a fetal or embryonic form

and a peri- or postnatal form. In infants with the less common fetal variant (∼10%-25% of cases) cholestasis with acholic stools is present from birth with no jaundice-free interval after resolution of normal physiological hyperbilirubinemia. At the time of exploratory laparotomy, little or none of http://www.selleckchem.com/products/r428.html the extrahepatic biliary structures can be found in the hepatic hilum, and there are often associated malformations such as the polysplenia syndrome and abdominal situs inversus. In contrast, in click here the postnatal form there is progressive inflammatory destruction of the extrahepatic biliary tract in a baby appearing healthy in the first weeks of life. Clinical features support the concept that in most cases injury to the biliary tract occurs after biliary morphogenesis usually after birth. In practice, differentiation of

these clinical forms on the basis of the onset of liver dysfunction and occurrence of congenital malformations is inexact. Indeed, a recent study showed that over half of patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth.5 The cause of biliary atresia is unknown. Several mechanisms have been proposed to account for the progressive obliteration of the extrahepatic biliary tree. There is no evidence that biliary atresia results from a failure in morphogenesis in the majority of affected infants or from an ischemic or toxic injury to the bile ducts. There is emerging, convincing evidence for initiation of the process probably in response to a common viral infection or unknown environmental factor in a genetically susceptible host. A dysregulated cellular, humoral, and innate immune response all seem to be involved based on studies in humans and a mouse model of the disease.

0 (CTM) assays Results: Discordant test results for HCV RNA dete

0 (CTM) assays. Results: Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on treatment. The ART

detected HCV RNA in 41% of week 4 samples classified as negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of samples who met stopping rules by CTM the ART measured Rapamycin levels below the respective cut-offs of 100 or 1000 IU/ml for boceprevir or telaprevir-based therapy, respectively, which would have allowed treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued

due to detectable residual HCV RNA by the ART assay. Still, only four of these patients failed to achieve SVR. Conclusion: Both assays are in principle suitable to predict treatment outcome and to determine treatment http://www.selleckchem.com/screening/fda-approved-drug-library.html decisions. However, significant discordance at early stages of treatment needs to be considered. Application of identical stopping rules determined in approval studies by one assay to other HCV RNA assays may lead to over and undertreatment in a significant number of patients. Detectable residual HCV RNA (<12 IU/ml) at week 24 in the ART i.e. might not be considered as necessary

stopping rule during PI based selleck compound triple therapy. Disclosures: Benjamin Maasoumy – Advisory Committees or Review Panels: Abbott Molecular, Janssen-Cilaq; Grant/Research Support: Abbott Molecular; Speaking and Teaching: MSD, Roche Diagnostics, Roche Pharma, Janssen-Cilaq, Fujirebio Bela Hunyady – Advisory Committees or Review Panels: MSD, AbbVie, Janssen; Speaking and Teaching: Roche, Fresenius-Kabi Michael Makara – Advisory Committees or Review Panels: MSD, BMS, Gilead; Consulting: MSD, Roche, Janssen; Grant/Research Support: Janssen, Idera, Novartis, Boehringer Ingelheim Gavin A. Cloherty – Employment: Abbott Molecular; Stock Shareholder: Abbott Laboratories Michael P.

Latitude and longitude were correlated, so to avoid multicollinea

Latitude and longitude were correlated, so to avoid multicollinearity we used the first principal component of these two variables as our geographic factor. This principal component explained 84% of the variance in latitude and longitude. We used the same model to test for elevation effects on each of the three song features by removing the geographic

factor and replacing it with elevation values for the site of each recording. We ran these three tests separately from the previous three because the geographic factor was correlated with elevation. All statistics were performed in jmp version 9.0 (SAS Institute Inc., Cary, NC, USA, MEK inhibitor 2010). All measured songs were discrete and brief with breaks between songs lasting at least 1 s. All birds sang songs that included one or two introductory

note types, followed by a more complex end phrase that often ran into a trill (Figs 2-4). Selleck Y-27632 Songs with two different introductory note types were rare, and 87% of songs included only two syllable types: an introductory note repeated up to six times, followed by an end phrase that was sometimes repeated more than once. We observed three general introductory note types: (1) a descending frequency sweep (46 birds); (2) a broadband buzz (32 birds); (3) a harmonic stack (5 birds) (Fig. 2). Nineteen birds sang multiple introductory note types, with one singing all three introductory notes. Acoustically, these notes were not all identical among individuals, but were clearly identifiable to type. Song end phrases showed much more diversity in form than introductory notes (Fig. 3). We identified 77 end-phrase types. Of these, 42 were unique to single birds; the remaining 35 end phrases were shared by two to seven individuals each. Frequency characteristics of the three introductory note types, end phrases and whole songs are detailed in Table 1. In total, we identified 179 song types from the 61 recorded birds. The largest recorded repertoire

of an individual included 16 song types and 15 syllable types. Individuals typically sang with eventual variety. Longer recordings contained click here more song types (Appendix S1), and all recorded birds continued to produce new song and end-phrase types up to the end of each recording. Thus, we expect that more extensive sampling would discover more song types from every individual. Song bouts may include a wide variety of song forms generated by altering (1) the type of introductory note; (2) the number of repetitions of the introductory note; (3) the type of end phrase; (4) the number of repetitions of the end phrase; (5) the addition of a third note type (Fig. 4). On a local scale, songs were highly varied: multiple tracks (n = 2–4) from nine common locations did not show evidence of song sharing by neighbours.