A randomised trial evaluating Bevacizumab as adjuvant therapy following resection of AJCC stage IIB, IIC and III cutaneous melanoma : an update

At present, there are no standard therapies for the adjuvant treatment of malignant melanoma. Patients with primary tumours with a high-Breslow thickness (stages IIB and IIC) or with resected loco-regional nodal disease (stage III) are at high risk of developing metastasis and subsequent disease-related death. Given this, it is important that novel therapies are investigated in the adjuvant melanoma setting. Since angiogenesis is essential for primary tumour growth and the development of metastasis, anti-angiogenic agents are attractive potential therapeutic candidates for clinical trials in the adjuvant setting. Therefore, we initiated a phase II trial in resected high-risk cutaneous melanoma, assessing the efficacy of bevacizumab versus observation. In the interim safety data analysis, we demonstrate that bevacizumab is a safe therapy in the adjuvant melanoma setting with no apparent increase in the surgical complication rate after either primary tumour resection and/or loco-regional lymphadenectomy

Is It Easy to Be Urban? Convergent Success in Urban Habitats among Lineages of a Widespread Native Ant

The most rapidly expanding habitat globally is the urban habitat, yet the origin and life histories of the populations of native species that inhabit this habitat remain poorly understood. We use DNA barcoding of the COI gene in the widespread native pest ant Tapinoma sessile to test two hypotheses regarding the origin of urban populations and traits associated with their success. First, we determine if urban samples of T. sessile have a single origin from natural populations by looking at patterns of haplotype clustering from across their range. Second, we examine whether polygynous colony structure – a trait associated with invasion success – is correlated with urban environments, by studying the lineage dependence of colony structure. Our phylogenetic analysis of 49 samples identified four well supported geographic clades. Within clades, Kimura-2 parameter pairwise genetic distances revealed <2.3% variation; however, between clade genetic distances were 7.5–10.0%, suggesting the possibility of the presence of cryptic species. Our results indicate that T. sessile has successfully colonized urban environments multiple times. Additionally, polygynous colony structure is a highly plastic trait across habitat, clade, and haplotype. In short, T. sessile has colonized urban habitats repeatedly and appears to do so using life history strategies already present in more natural populations. Whether similar results hold for other species found in urban habitats has scarcely begun to be considered

Circulating tumor DNA predicts survival in patients with resected high risk stage II/III melanoma

Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. Patients and methods: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. Results: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79–5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80–5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83–5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88–6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%–55%) versus 65% (95% CI 56%–72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40–4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32–4.74, P = 0.005). Conclusion: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy

The Global Ant Genomics Alliance (GAGA)

Peer reviewe

Relationships of Risk Factors for Pre-Eclampsia with Patterns of Occurrence of Isolated Gestational Proteinuria during Normal Term Pregnancy

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (&lt;= 20 weeks gestation), and onset at 21-28 weeks, 29-32 weeks, 33-36 weeks and &gt;= 37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of preeclampsia.&lt;/p&gt

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study

Background Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis. Methods We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7·5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratifi ed by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306. Findings 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16ñ37) in the bevacizumab group and 25 months (17ñ37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no signifi cant di┎ erence in overall survival between treatment groups (hazard ratio [HR] 0·97, 95% CI 0·78ñ1·22; p=0·76); this fi nding persisted after adjustment for stratifi cation variables (HR 1·03; 95% CI 0·81ñ1·29; p=0·83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21ñ52) and dose intensity was 86% (41ñ96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [<1%]). There was an improvement in disease-free interval for patients in the bevacizumab group compared with those in the observation group (HR 0·83, 95% CI 0·70ñ0·98, p=0·03), but no signifi cant di┎ erence between groups for distant-metastasis-free interval (HR 0·88, 95% CI 0·73ñ1·06, p=0·18). No signifi cant di┎ erences were noted between treatment groups in the standardised area under the curve for any of the quality-of-life scales over 36 months. Three adverse drug reactions were regarded as both serious and unexpected: one patient had optic neuritis after the fi rst bevacizumab infusion, a second patient had persistent erectile dysfunction, and a third patient died of a haemopericardium after receiving two bevacizumab infusions and was later identifi ed to have had signifi cant predisposing cardiovascular risk factors. Interpretation Bevacizumab has promising tolerability. Longer follow-up is needed to identify an e┎ect on the primary endpoint of overall survival at 5 years. Funding Cancer Research U

Testing a Short Nuclear Marker for Inferring Staphylinid Beetle Diversity in an African Tropical Rain Forest

The use of DNA based methods for assessing biodiversity has become increasingly common during the last years. Especially in speciose biomes as tropical rain forests and/or in hyperdiverse or understudied taxa they may efficiently complement morphological approaches. The most successful molecular approach in this field is DNA barcoding based on cytochrome c oxidase I (COI) marker, but other markers are used as well. Whereas most studies aim at identifying or describing species, there are only few attempts to use DNA markers for inventorying all animal species found in environmental samples to describe variations of biodiversity patterns.In this study, an analysis of the nuclear D3 region of the 28S rRNA gene to delimit species-like units is compared to results based on distinction of morphospecies. Data derived from both approaches are used to assess diversity and composition of staphylinid beetle communities of a Guineo-Congolian rain forest in Kenya. Beetles were collected with a standardized sampling design across six transects in primary and secondary forests using pitfall traps. Sequences could be obtained of 99% of all individuals. In total, 76 molecular operational taxonomic units (MOTUs) were found in contrast to 70 discernible morphospecies. Despite this difference both approaches revealed highly similar biodiversity patterns, with species richness being equal in primary and secondary forests, but with divergent species communities in different habitats. The D3-MOTU approach proved to be an efficient tool for biodiversity analyses.Our data illustrate that the use of MOTUs as a proxy for species can provide an alternative to morphospecies identification for the analysis of changes in community structure of hyperdiverse insect taxa. The efficient amplification of the D3-marker and the ability of the D3-MOTUs to reveal similar biodiversity patterns as analyses of morphospecies recommend its use in future molecular studies on biodiversity

The Antiquity and Evolutionary History of Social Behavior in Bees

A long-standing controversy in bee social evolution concerns whether highly eusocial behavior has evolved once or twice within the corbiculate Apidae. Corbiculate bees include the highly eusocial honey bees and stingless bees, the primitively eusocial bumble bees, and the predominantly solitary or communal orchid bees. Here we use a model-based approach to reconstruct the evolutionary history of eusociality and date the antiquity of eusocial behavior in apid bees, using a recent molecular phylogeny of the Apidae. We conclude that eusociality evolved once in the common ancestor of the corbiculate Apidae, advanced eusociality evolved independently in the honey and stingless bees, and that eusociality was lost in the orchid bees. Fossil-calibrated divergence time estimates reveal that eusociality first evolved at least 87 Mya (78 to 95 Mya) in the corbiculates, much earlier than in other groups of bees with less complex social behavior. These results provide a robust new evolutionary framework for studies of the organization and genetic basis of social behavior in honey bees and their relatives

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

Aim: Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location: Global. Methods: We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results: Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions: Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.Fil: Kot, Connie Y.. University of Duke; Estados UnidosFil: Åkesson, Susanne. Lund University; SueciaFil: Alfaro Shigueto, Joanna. Universidad Cientifica del Sur; Perú. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Amorocho Llanos, Diego Fernando. Research Center for Environmental Management and Development; ColombiaFil: Antonopoulou, Marina. Emirates Wildlife Society-world Wide Fund For Nature; Emiratos Arabes UnidosFil: Balazs, George H.. Noaa Fisheries Service; Estados UnidosFil: Baverstock, Warren R.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Blumenthal, Janice M.. Cayman Islands Government; Islas CaimánFil: Broderick, Annette C.. University of Exeter; Reino UnidoFil: Bruno, Ignacio. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Canbolat, Ali Fuat. Hacettepe Üniversitesi; Turquía. Ecological Research Society; TurquíaFil: Casale, Paolo. Università degli Studi di Pisa; ItaliaFil: Cejudo, Daniel. Universidad de Las Palmas de Gran Canaria; EspañaFil: Coyne, Michael S.. Seaturtle.org; Estados UnidosFil: Curtice, Corrie. University of Duke; Estados UnidosFil: DeLand, Sarah. University of Duke; Estados UnidosFil: DiMatteo, Andrew. CheloniData; Estados UnidosFil: Dodge, Kara. New England Aquarium; Estados UnidosFil: Dunn, Daniel C.. University of Queensland; Australia. The University of Queensland; Australia. University of Duke; Estados UnidosFil: Esteban, Nicole. Swansea University; Reino UnidoFil: Formia, Angela. Wildlife Conservation Society; Estados UnidosFil: Fuentes, Mariana M. P. B.. Florida State University; Estados UnidosFil: Fujioka, Ei. University of Duke; Estados UnidosFil: Garnier, Julie. The Zoological Society of London; Reino UnidoFil: Godfrey, Matthew H.. North Carolina Wildlife Resources Commission; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: González Carman, Victoria. Instituto National de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harrison, Autumn Lynn. Smithsonian Institution; Estados UnidosFil: Hart, Catherine E.. Grupo Tortuguero de las Californias A.C; México. Investigacion, Capacitacion y Soluciones Ambientales y Sociales A.C; MéxicoFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Hays, Graeme C.. Deakin University; AustraliaFil: Hill, Nicholas. The Zoological Society of London; Reino UnidoFil: Hochscheid, Sandra. Stazione Zoologica Anton Dohrn; ItaliaFil: Kaska, Yakup. Dekamer—Sea Turtle Rescue Center; Turquía. Pamukkale Üniversitesi; TurquíaFil: Levy, Yaniv. University Of Haifa; Israel. Israel Nature And Parks Authority; IsraelFil: Ley Quiñónez, César P.. Instituto Politécnico Nacional; MéxicoFil: Lockhart, Gwen G.. Virginia Aquarium Marine Science Foundation; Estados Unidos. Naval Facilities Engineering Command; Estados UnidosFil: López-Mendilaharsu, Milagros. Projeto TAMAR; BrasilFil: Luschi, Paolo. Università degli Studi di Pisa; ItaliaFil: Mangel, Jeffrey C.. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Margaritoulis, Dimitris. Archelon; GreciaFil: Maxwell, Sara M.. University of Washington; Estados UnidosFil: McClellan, Catherine M.. University of Duke; Estados UnidosFil: Metcalfe, Kristian. University of Exeter; Reino UnidoFil: Mingozzi, Antonio. Università Della Calabria; ItaliaFil: Moncada, Felix G.. Centro de Investigaciones Pesqueras; CubaFil: Nichols, Wallace J.. California Academy Of Sciences; Estados Unidos. Center For The Blue Economy And International Environmental Policy Program; Estados UnidosFil: Parker, Denise M.. Noaa Fisheries Service; Estados UnidosFil: Patel, Samir H.. Coonamessett Farm Foundation; Estados Unidos. Drexel University; Estados UnidosFil: Pilcher, Nicolas J.. Marine Research Foundation; MalasiaFil: Poulin, Sarah. University of Duke; Estados UnidosFil: Read, Andrew J.. Duke University Marine Laboratory; Estados UnidosFil: Rees, ALan F.. University of Exeter; Reino Unido. Archelon; GreciaFil: Robinson, David P.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Robinson, Nathan J.. Fundación Oceanogràfic; EspañaFil: Sandoval-Lugo, Alejandra G.. Instituto Politécnico Nacional; MéxicoFil: Schofield, Gail. Queen Mary University of London; Reino UnidoFil: Seminoff, Jeffrey A.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Seney, Erin E.. University Of Central Florida; Estados UnidosFil: Snape, Robin T. E.. University of Exeter; Reino UnidoFil: Sözbilen, Dogan. Dekamer—sea Turtle Rescue Center; Turquía. Pamukkale University; TurquíaFil: Tomás, Jesús. Institut Cavanilles de Biodiversitat I Biologia Evolutiva; EspañaFil: Varo Cruz, Nuria. Universidad de Las Palmas de Gran Canaria; España. Ads Biodiversidad; España. Instituto Canario de Ciencias Marinas; EspañaFil: Wallace, Bryan P.. University of Duke; Estados Unidos. Ecolibrium, Inc.; Estados UnidosFil: Wildermann, Natalie E.. Texas A&M University; Estados UnidosFil: Witt, Matthew J.. University of Exeter; Reino UnidoFil: Zavala Norzagaray, Alan A.. Instituto politecnico nacional; MéxicoFil: Halpin, Patrick N.. University of Duke; Estados Unido

Macroevolutionary Patterns in the Aphidini Aphids (Hemiptera: Aphididae): Diversification, Host Association, and Biogeographic Origins

, the most diverse genus in the family. We used a combined dataset of one nuclear and four mitochondrial DNA regions. A molecular dating approach, calibrated with fossil records, was used to estimate divergence times of these taxa.Most generic divergences in Aphidini occurred in the Middle Tertiary, and species-level divergences occurred between the Middle and Late Tertiary. The ancestral state of host use for Aphidini was equivocal with respect to three states: monoecy on trees, heteroecy, and monoecy on grasses. The ancestral state of Rhopalosiphina likely included both heteroecy and monoecy, whereas that of Aphidina was most likely monoecy. The divergence times of aphid lineages at the generic or subgeneric levels are close to those of their primary hosts. The species-level divergences in aphids are consistent with the diversification of the secondary hosts, as a few examples suggest. The biogeographic origin of Aphidini as a whole was equivocal, but the major lineages within Aphidina likely separated into Nearctic, Western Palearctic, and Eastern Palearctic regions.Most generic divergences in Aphidini occurred in the Middle Tertiary when primary hosts, mainly in the Rosaceae, were diverging, whereas species-level divergences were contemporaneous with diversification of the secondary hosts such as Poaceae in the Middle to Late Tertiary. Our results suggest that evolution of host alternation within Aphidini may have occurred during the Middle Tertiary (Oligocene) when the secondary hosts emerged