Reproductive character displacement: insights from genital morphometrics in damselfly hybrid zones.

Reproductive Character Displacement (RCD) refers to the phenomenon of greater differences in reproductive characters between two species when they occur in sympatry compared to when they occur in allopatry to prevent maladaptive hybridization. We explored whether reinforcement of a mechanical barrier involved in the first contact point between male and female genital traits during copulation in the cross between Ischnura graellsii males and Ischnura elegans females has led to RCD, and whether it supports the lock-and-key hypothesis of genital evolution. We employed geometric morphometrics to analyze the shape and size of male and female genital traits, controlling for environmental and geographic factors. Consistent with an increase in mechanical isolation via reinforcement, we detected larger divergence in genital traits between the species in sympatry than in allopatry, and also stronger signal in females than in males. In the Northwest (NW) hybrid zone, we detected RCD in I. graellsii males and I. elegans females, while in the Northcentral (NC) hybrid zone we detected RCD only in I. elegans females and I. elegans males. The detection of RCD in both sexes of I. elegans was consistent with the lock-and-key hypothesis of genital evolution via female choice for conspecific males in this species. Our study highlights the importance of using geometric morphometrics to deal with the complexity of female reproductive structures while controlling for environmental and geographic factors to investigate RCD. This study contributes valuable insights into the dynamics of reproductive isolation mechanisms and genital coevolution.

Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine.

BACKGROUND: This analysis characterizes the immunogenicity profile of galcanezumab, a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and inhibits its activity, in phase 3 migraine trials. METHODS: Immunogenicity data were analyzed from baseline and double-blind, placebo-controlled phases of the 3-month chronic migraine study REGAIN, the 6-month episodic migraine studies EVOLVE-1 and EVOLVE-2, and from baseline and open-label phases of the 12-month chronic and episodic migraine Study CGAJ. The incidence of baseline antidrug antibodies, treatment-emergent antidrug antibodies, neutralizing antidrug antibodies, and the effect of antidrug antibody titer on pharmacokinetics and pharmacodynamics were assessed. The relationship between antidrug antibody status and efficacy was explored using average change in monthly migraine headache days. Safety analyses assessed the potential relationship between treatment-emergent antidrug antibodies and hypersensitivity events or adverse events related to injection sites. FINDINGS: Across studies, 5.9-11.2% of patients had baseline antidrug antibodies. The incidence of treatment-emergent antidrug antibodies was 2.6-12.4% in the galcanezumab group and 0.5-1.7% in the placebo group. The majority of treatment-emergent antidrug antibodies were detected approximately 3-6 months after first study drug dose. Overall, the observed antidrug antibody titer did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or galcanezumab efficacy. There was no evidence that hypersensitivity events or adverse events related to injection sites were mediated by treatment-emergent antidrug antibodies. INTERPRETATION: These data showed that immunogenicity did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or the efficacy and hypersensitivity profile of galcanezumab in patients with migraine.

A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies.

INTRODUCTION: Clinical remission is today the treatment goal for rheumatoid arthritis (RA), which requires fast and assertive therapeutic decisions for a tight control of disease activity. Few objective parameters are available to guide clinical decisions, particularly in switcher patients. We designed a preliminary algorithm introducing immunogenicity assessment in the current approach to patients with RA receiving tumour necrosis factor inhibitors (TNFi). OBJECTIVE: To evaluate the concordance between the new algorithm and current clinical practice, comparing the effectiveness of 'immunogenicity-based' versus 'empirical-based' switches in a cohort of patients with established RA receiving biologics. METHODS: EULAR therapeutic response was evaluated in 105 patients with RA (naive or switchers) over one year, through generalised estimation equation (GEE) analyses. Serum drug trough levels were assessed by ELISA and antidrug antibodies (ADAb) by Bridging ELISA. RESULTS: During follow-up, 48.6% of patients had therapeutic decisions concordant with the proposed algorithm (Group A), and 51.4% had discordant decisions (Group B). One year after the therapeutic decision, patients from Group A had a higher probability of achieving response (OR=7.91, p<0.001, 95% CI 3.27 to 19.13) and low disease activity (OR=9.77, p<0.001, 95% CI 4.69 to 20.37) than patients in Group B. CONCLUSIONS: Immunogenicity assessment might help to optimise therapeutic decisions, leading to a better control of disease activity with significantly better clinical outcomes in patients with RA receiving TNFi.

Molecular and morphological data suggest a new species of big-eared bat (Vespertilionidae: Corynorhinus) endemic to northeastern Mexico.

Corynorhinus mexicanus is an insectivorous bat endemic to Mexico that inhabits the high and humid regions of the Sierra Madre Oriental (SMO), the Trans-Mexican Volcanic Belt (TMVB), and the Sierra Madre Occidental (SMOC). A previous study suggested that C. mexicanus could be a cryptic species complex due to the genetic divergence observed between specimens from the TMVB and SMOC. The present study implemented phylogenetic, population genetics, and morphological analyses to evaluate the hypothesis that C. mexicanus is a species complex. The phylogenetic analysis indicated that C. mexicanus is a polyphyletic species composed of three indirectly related lineages. The estimated divergence times for the lineages suggest that they first originated during the Pliocene, while the second and third shared a common ancestor with C. townsendii 1.55 million years ago, and diverged 600,000 years ago during the Middle Pleistocene. The population genetics analysis reveals the SMO lineage of C. mexicanus is an isolated genetic group and highly diverged from the rest of lineages (SMOC and TMVB). The morphological analyses showed variation in the skull and mandible associated with the lineages and sex of the specimens, highlighting a difference in mandible shape between the specimens of the SMO and the rest of C. mexicanus. The results of this study suggest the presence of an undescribed species of the genus Corynorhinus.

The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis.

BACKGROUND: Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. OBJECTIVE: To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. DATA SOURCES: PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). STUDY SELECTION: Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). DATA EXTRACTION: Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. DATA SYNTHESIS: Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): <74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). CONCLUSIONS: ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.

Improving resource utilisation in SLE drug development through innovative trial design.

SLE is a complex autoimmune disease with considerable unmet need. Numerous clinical trials designed to investigate novel therapies are actively enrolling patients straining limited resources and creating inefficiencies that increase enrolment challenges. This has motivated investigators developing novel drugs and treatment strategies to consider innovative trial designs that aim to improve the efficiency of generating evidence; these strategies propose conducting fewer trials, involving smaller numbers of patients, while maintaining scientific rigour in safety and efficacy data collection and analysis. In this review we present the design of two innovative phase IIb studies investigating efavaleukin alfa and rozibafusp alfa for the treatment of SLE which use an adaptive study design. This design was selected as a case study, investigating efavaleukin alfa, in the Food and Drug Administration's Complex Innovative Trial Design Pilot Program. The adaptive design approach includes prospectively planned modifications at predefined interim timepoints. Interim assessments of futility allow for a trial to end early when the investigational therapy is unlikely to provide meaningful treatment benefits to patients, which can release eligible patients to participate in other-potentially more promising-trials, or seek alternative treatments. Response-adaptive randomisation allows randomisation ratios to change based on accumulating data, in favour of the more efficacious dose arm(s), while the study is ongoing. Throughout the trial the placebo arm allocation ratio is maintained constant. These design elements can improve the statistical power in the estimation of treatment effect and increase the amount of safety and efficacy data collected for the optimal dose(s). Furthermore, these trials can provide the required evidence to potentially serve as one of two confirmatory trials needed for regulatory approval. This can reduce the need for multiple phase III trials, the total patient requirements, person-exposure risk, and ultimately the time and cost of investigational drug development programmes.

Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by pathological processes involving autoimmunity, vasculopathy and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper, we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluate the binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera was evaluated for the potential to activate keratinocytes in tissue culture and to induce TLR2 and 3 signalling in reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes and the activation of these cells leading to the release of IL-1α, representing a potential initiating pathway in this disease.

Species delimitation and integrative taxonomy of the Reithrodontomys mexicanus (Rodentia: Cricetidae) cryptic complex.

Species boundaries are difficult to establish in groups with very similar morphology. As an alternative, it has been suggested to integrate multiple sources of data to clarify taxonomic problems in taxa where cryptic speciation processes have been reported. This is the case of the harvest mouse Reithrodontomys mexicanus, which has a problematic taxonomy history as it is considered a complex species. Here, we evaluate the cryptic diversity of R. mexicanus using an integrative taxonomy approach in order to detect candidate lineages at the species level. The molecular analysis used one mitochondrial (cytb) and two nuclear (Fgb-I7 and IRBP) genes. Species hypotheses were suggested based on three molecular delimitation methods (mPTP, bGMYC, and STACEY) and cytb genetic distance values. Skull and environmental space differences between the delimited species were also tested to complement the discrimination of candidate species. Based on the consensus across the delimitation methods and genetic distance values, four species were proposed, which were mostly supported by morphometric and ecological data: R. mexicanus clade I, R. mexicanus clade IIA, R. mexicanus clade IIIA, and R. mexicanus clade IIIB. In addition, the evolutionary relationships between the species that comprise the R. mexicanus group were discussed from a phylogenetic approach. Our findings present important taxonomic implications for Reithrodontomys, as the number of known species for this genus increases. Furthermore, we highlight the importance of the use of multiple sources of data in systematic studies to establish robust delimitations between species considered taxonomically complex.

Geometric morphometrics and ecological niche modelling for delimitation of Triatoma pallidipennis (Hemiptera: Reduviidae: Triatominae) haplogroups.

A recent phylogenetic analysis of Triatoma pallidipennis, an important Chagas disease vector in Mexico, based on molecular markers, revealed five monophyletic haplogroups with validity as cryptic species. Here, we compare T. pallidipennis haplogroups using head and pronotum features, environmental characteristics of their habitats, and ecological niche modeling. To analyze variation in shape, images of the head and pronotum of the specimens were obtained and analyzed using methods based on landmarks and semi-landmarks. Ecological niche models were obtained from occurrence data, as well as a set of bioclimatic variables that characterized the environmental niche of each analyzed haplogroup. Deformation grids for head showed a slight displacement towards posterior region of pre-ocular landmarks. Greatest change in head shape was observed with strong displacement towards anterior region of antenniferous tubercle. Procrustes ANOVA and pairwise comparisons showed differences in mean head shape in almost all haplogroups. However, pairwise comparisons of mean pronotum shape only showed differences among three haplogroups. Correct classification of all haplogroups was not possible using discriminant analysis. Important differences were found among the environmental niches of the analyzed haplogroups. Ecological niche models of each haplogroup did not predict the climatic suitability areas of the other haplogroups, revealing differences in environmental conditions. Significant differences were found between at least two haplogroups, demonstrating distinct environmental preferences among them. Our results show how the analysis of morphometric variation and the characterization of the environmental conditions that define the climatic niche can be used to improve the delimitation of T. pallidipennis haplogroups that constitute cryptic species.

Towards a novel clinical outcome assessment for systemic lupus erythematosus: first outcomes of an international taskforce.

Systemic lupus erythematosus (SLE) is a disease of high unmet therapeutic need. The challenge of accurately measuring clinically meaningful responses to treatment has hindered progress towards positive outcomes in SLE trials, impeding the approval of potential new therapies. Current primary end points used in SLE trials are based on legacy disease activity measures that were neither specifically designed for the clinical trial context, nor developed according to contemporary recommendations for clinical outcome assessments (COAs), such as that substantial patient input should be incorporated into their design. The Treatment Response Measure for SLE (TRM-SLE) Taskforce is a global collaboration of SLE clinician-academics, patients and patient representatives, industry partners and regulatory experts, established to realize the goal of developing a new COA for SLE clinical trials. The aim of this project is a novel COA designed specifically to measure treatment effects that are clinically meaningful to patients and clinicians, and intended for implementation in a trial end point that supports regulatory approval of novel therapeutic agents in SLE. This Consensus Statement reports the first outcomes of the TRM-SLE project, including a structured process for TRM-SLE development.

Morphometric tools to solve species complexes: The case of Rhagovelia angustipes (Hemiptera: Veliidae).

The riffle bugs of the Rhagovelia angustipes complex have presented problems in taxonomy due to high intra-specific variability. Here we identified variation in the complex with morphometric techniques. We analyzed variation of the characters and performed a phylogenetic analysis of a combined matrix of linear measurements, geometric configurations, and discrete characters. We found that characters such as head length, metanotum length, femur width, and the evaluated shape of four characters (head, abdomen, fore tibia, hind femur) were important for the delimitation of species. In particular, we identified the metanotum length as a character that had not been previously considered in the taxonomy of the complex. The phylogenetic reconstruction allowed us to recover some relationships established for the taxonomy of the complex for the salina group, except for the species R. colombiana that was closer to R. calceola and R. calopa. This may be due to a similar natural history, since they share areas of distribution, while the R. bisignata and R. hambletoni groups could not be recovered, showing their low morphological support. In general, the geometric morphometric characters showed high levels of homology, with the head and the anterior tibia being the ones that had the best performance in the tree. Finally, the use of morphometric tools proved to be a powerful input for the taxonomic resolution of species complexes that have problems in their delimitation.

Body shape and fluctuating asymmetry following different feeding sources and feeding time in a triatomine, Triatoma pallidipennis (Stål, 1892).

Even when an animal has a generalist diet, different food sources can impact its body shape and fluctuating asymmetry (a stress indicator; FA). To test this, we varied the food source (mammalian, avian or defibrinated mammalian blood; and control animals - ad libitum feeding) and the time of feeding (every 8 days, 45 days and ad libitum) having the Chagas triatomine vector, Triatoma pallidipennis (Stål, 1892), as a study animal which has presumable generalist feeding habits. This factorial design was applied since first instar animals until adulthood. As response variables, we measured body shape and FA in adults of both sexes, using a two-dimensional geometric morphometrics protocol. The highest variance in body shape was explained by diet (17%), followed by sex nested within diet (12%). Males had less morphological differentiation than females: females with defibrinated blood provided every 45 days differentiated more, while those that fed on mammalian blood every 8 days differed less. Distances among the averages of the FA component related to shape indicated greater distances between avian blood provided every 45 days and mammalian blood provided every 8 days, as well as between the two groups fed on avian blood (feeding every 8 and 45 days), followed by avian and defibrinated blood, both fed every 8 days. These results indicate that blood source and feeding time have significant effects on the body shape, and FA in females and both sexes. Thus, despite general feeding habits, avian blood showed a greater impact on shape and FA in triatomines. This may select for triatomines to use mammal blood rather than avian blood if they have the chance to do so.

Growth temperature effect on mandibles' ontogeny and sexual dimorphism in the ambrosia beetle Xyleborus affinis (Curculionidae: Scolytinae).

Ambrosia beetles from the genus Xyleborus are important vectors of fungal pathogens in forest and agricultural systems, yet the influence of temperature on their morphological development has been poorly studied. Because host colonization and ambrosial fungi cultivation is mostly restricted to females, it is possible to speculate on strong sexual dimorphism expression in secondary sexual characters and ecological segregation between sexes. Here, we determined the effect of different growing temperatures (17, 23, 26 and 29 °C) on mandible ontogeny of larvae and adult individuals of X. affinis, and sexual dimorphism in adults, in shape and size variation using geometric morphometrics. Mandible shape change showed significant differences in magnitude and direction through larval ontogeny among temperature treatments. Sexual shape and size dimorphism were found in adult mandibles, and the degree of sexual dimorphism was dependent on growth temperature, with a significant effect of the interaction between temperature and sex on mandible shape and size variation. Higher morphological differences were observed at the base of mandibles among temperature treatments in adults and a gradual narrowing trend with temperature increments. These findings could have consequences on feeding performance and fungus cultivation inside colonies, potentially influencing their ability to establish populations in new geographical areas.

The Immunogenicity of Biologic Therapies.

Virtually all therapeutic proteins (biologics) elicit an immune response with the consequent production of anti-drug antibodies (ADA). The majority of ADA to therapeutic monoclonal antibodies (mAbs) are directed against the antigen-binding site of the therapeutic mAb, and hence are neutralizing. This nature of the ADA response explains why fully human antibodies can still be highly immunogenic. The detection of ADA is technically challenging and all assays have limitations, namely a limited capacity in detecting ADA in the presence of a drug due to immune complex (IC) formation, which may underestimate the ADA incidence. Refined assays, able to disrupt drug-ADA ICs, have revealed the presence of ADA in a higher proportion of patients. The great heterogeneity among ADA assays prevents a direct comparison of immunogenicity between different molecules and across studies. The formation of drug-ADA ICs can significantly alter pharmacokinetics and directly reduce drug efficacy if the ADA titer (i.e., concentration) is sufficiently high and persistent. In patients with low ADA titer, free drug concentrations may remain high enough to be effective, while in patients developing high ADA titer a substantial part of the drug will be neutralized and clinical non-response is likely to occur. ADA can also increase the risk of adverse events, namely hypersensitivity reactions. Several studies have revealed the presence of ADA before a clinically overt adverse reaction, highlighting their predictive value. Algorithms integrating therapeutic drug monitoring and immunogenicity information in the current clinical evaluation of patients receiving biologics are today available to guide therapeutic decisions in clinical practice, helping us to design safer and more cost-effective therapeutic strategies.

Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate to Severe Plaque Psoriasis.

Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is efficacious for moderate to severe plaque psoriasis. We examined relationships between serum ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADAs), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosage of 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA-positive patients (17.4%, n = 65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to those of TE-ADA-negative patients. Nine patients (2.4%) developed high titers, with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177.

Head shape variation in cerambycid saproxylic beetles as a function of host plant selection.

Saproxylic insects depend on deadwood for larval development, and a certain degree of specialization may be involved in their choice of host plants and/or wood in a particular stage of degradation. The plant species chosen for oviposition in turn act as an environmental pressure on the head morphology of larvae and it is expected that head shape plasticity varies directly with the number of woody plant species used for larval development in each insect species. We analyzed head shape variation in saproxylic beetles with respect to host plant species, maximum time of larval emergence and season of the year when insects colonized branches. Generalist species in the use of host plants showed significant variation in head shape and size. Time of emergence and season did not appear to affect head shape, although season was a determinant factor of abundance and possibly head size variation.

Managing unwanted immunogenicity of biologicals.

All protein drugs (biologicals) have an immunogenic potential and we are armed with multiple guidelines, regulatory documents and white papers to assist us in assessing the level of risk for unwanted immunogenicity of new biologicals. However, for certain biologicals, significant immunogenicity becomes only apparent after their use in patients. Causes of immunogenicity are multifactorial but not yet fully understood. Within the pharmaceutical industry there are only a few opportunities to openly discuss the causes and consequences of immunogenicity with regard to the development of new biologicals. The annual Open Scientific Symposium of the European Immunogenicity Platform (EIP) is one such meeting that brings together scientists and clinicians from academia and industry to build know-how and expertise in the field of immunogenicity. The critical topics discussed at the last EIP meeting (February 2014) will be reviewed here. The current opinion of this expert group is that the assessment of unwanted immunogenicity can be improved by using prediction tools, optimizing the performance of immunogenicity assays and learning from the clinical impact of other biologicals that have already been administered to patients. A multidisciplinary approach is warranted to better understand and minimize drug immunogenicity and its clinical consequences.

The Portuguese Society of Rheumatology position paper on the use of biosimilars.

Biotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.

Bite force, cranial morphometrics and size in the fishing bat Myotis vivesi (Chiroptera: Vespertilionidae)

Abstract Fish-eating in bats evolved independently in Myotis vivesi (Vespertillionidae) and Noctilio leporinus (Noctilionidae). We compared cranial morphological characters and bite force between these species to test the existence of evolutionary parallelism in piscivory. We collected cranial distances of M. vivesi, two related insectivorous bats (M. velifer and M. keaysi), two facultatively piscivorous bats (M. daubentonii and M. capaccinii), and N. leporinus. We analyzed morphometric data applying multivariate methods to test for differences among the six species. We also measured bite force in M. vivesi and evaluated if this value was well predicted by its cranial size. Both piscivorous species were morphologically different from the facultatively piscivorous and insectivorous species, and skull size had a significant contribution to this difference. However, we did not find morphological and functional similarities that could be interpreted as parallelisms between M. vivesi and N. leporinus. These two piscivorous species differed significantly in cranial measurements and in bite force. Bite force measured for M. vivesi was well predicted by skull size. Piscivory in M. vivesi might be associated to the existence of a vertically displaced temporal muscle and an increase in gape angle that allows a moderate bite force to process food.(AU)

Resumen La alimentación por peces en murciélagos evolucionó independientemente en Myotis vivesi (Vespertilionidae) y Noctilio leporinus (Phyllostomidae). En este estudio se compararon características craneales morfológicas y fuerza de mordida entre estas especies, para probar la existencia de paralelismo evolucionario en piscivoría. Se recolectaron distancias craneales en M. vivesi, dos parientes insectívoros (M. velifer y M. keaysi), dos murciélagos piscívoros facultativos (M. daubentonii y M. capaccinii), y N. leporinus. Se analizaron datos morfométricos aplicando múltiples métodos para probar las diferencias entre las seis especies. Se midió la fuerza de mordida en M. vivesi y se evalúo si puede ser predicha por el tamaño del cráneo. Las especies piscívoras fueron morfológicamente diferentes de las facultativamente piscívoras y las insectívoras, el tamaño del cráneo tuvo una contribución significativa en esta diferencia. Sin embargo, no encontramos semejanzas morfológicas y funcionales que puedan ser interpretadas como paralelismos entre M. vivesi y N. leporinus. Estas dos especies piscívoras difieren significativamente en medidas craneales y fuerza de mordida. La fuerza de mordida en M. vivesi fue efectivamente predicha por el tamaño de cráneo. La piscivoría en M. vivesi puede estar asociada con la existencia de un músculo temporal verticalmente desplazado y el incremento en el ángulo de apertura mandibular que permite moderar la fuerza de mordida para procesar el alimento.(AU)

Tumor neuroectodérmico primitivo periférico extraesquelético/sarcoma de Ewing metastásico en un neonato / Metastatic primitive extraskeletal peripheral neurectodermal tumor/ewing sarcoma in a neonate / Tumor neuroectodérmico primitivo periférico extra esquelético/sarcoma de ewing apresentado em neonato

El tumor neuroectodérmico primitivo periférico/sarcoma de Ewing, descrito a comienzos del siglo XX, es un tumor muy maligno poco frecuente de gran mortalidad, cuya causa es la translocación t(11;22)(q24;q12) en células derivadas de la cuarta hojilla embrionaria o células de la cresta neural que, por su posibilidad de diferenciación en linajes mesenquimales craneocefálicos, fácilmente se convierte en metastásico. Se encuentra bajo la denominación de enfer- medades raras debido a su baja frecuencia de aparición. A nivel mundial se han referenciado, menos de 20 casos con afectación periférica extraósea congénita y este es el primero en reportarse en Colombia. En el presente caso se describe la lesión tumoral extraesquelética con metástasis a pulmón y a cerebro, en un neonato de sexo femenino, fruto de un embarazo único, prematuro, sin reporte de exposición a factores de riesgo medioam- bientales, que fue remitida con la lesión tumoral al segundo día de vida, por dificultad respiratoria grave progresiva a falla respiratoria. La bebé fue atendida en la unidad neonatal de la Fundación Cardioinfantil de Bogotá.

A female premature infant with no history of exposure, who on presented a peripheral primitive neuroectodermal tumor/extraosseous Ewing sarcoma with metastases to lungs and brain which rapidly invaded the airways. The knowledge of this exotic neoplasm could support the diagnosis and management of newborns with this rare tumor associated with respiratory failure and high mortality. This is the first newborn report of pPNET/Ewing sarcoma in South America, of which fewer than twenty cases have been published. Primitive neuroectodermal tumors or Ewing Sarcoma (PNET/ES) are an aggressive, rare and lethal tumor family of small blue cells with a varied histological morphology that affect the nervous system, skeleton, soft tissues, skin, or parenchymal organs. They are prevalent in the second decade of life, more frequent in whites, male/female 1.3-1.5:1, 85% are caused by nonrandom translocation t(11;22)(q24;q12) limited to the tumor, and therefore non-heritable, with chimeric EWS/FLI1 fusion and a positive CD99 immuno- phenotype. The reporting of this rare tumor associated with neonatal respiratory failure could facilitate its diag- nosis and early treatment.

O tumor neuroectodérmico primitivo periférico extra esquelético /Sarcoma de Ewing, descrito a inicios do século XX, é um tumor raro e maligno que apre-senta alto grau de mortalidade devido à translocação t(11;22)(q24;q12) em células derivadas da quarta hojilla embrionária ou crista neural que por possibilidade de diferenciação de linagens mesenquimales cráneocefá-lico, pode virar facilmente em metastasico.Trata-se de uma doença rara, debido à baixa frequência de aparição. Mundialmente tem se referenciado apro-ximadamente 15 eventos com afetação periférica extraóssea congênita e este é o primeiro caso reportado na Colômbia. No artigo se descreve a lesão tumoral extraesquelética com metastasis no pulmão e cérebro apresentado em neonato feminino produto de gravidez única pre-térmo sem reporte de exposição a fatores de risco medioambientais. O bebe foi remitido com lesão tumoral no segundo dia de ida, por ter apresentado difi-culdade respiratória progressiva grave e insuficiência ventilatória, foi atendida na unidade neonatal da Funda-cion Cardioinfantil (FCI-IC), na cidade de Bogotá.