Monozygotic twins discordant for Goldenhar syndrome

OBJECTIVE: To report on a pair of monozygotic female twins discordant for Goldenhar syndrome. DESCRIPTION: The affected twin was a girl, who was delivered by caesarean section at 35 weeks' gestation. Her birth weight was 2,170 g, length 42.5 cm, head circumference 30 cm and her Apgar scores were 3/7. After birth the child developed severe respiratory distress and had to be moved to the neonatal intensive care unit (ICU). The other twin was a girl, born weighing 3,200 g with a length of 49 cm, head circumference of 34 cm and Apgar scores of 8/10. She was transferred to the mother-baby unit soon after birth and was discharged two days later. There was no consanguinity between the twins' parents, who were young and healthy at the time of their conception. The affected child's dysmorphic features included left hemifacial microsomia, severe micrognathia, abnormal ears, bilateral preauricular tags and epibulbar dermoid in the right eye. She developed obstructive apnea due to micrognathia and required tracheostomy. Abdominal and cranial ultrasound findings were normal, as was an ophthalmological assessment. Spine x-ray showed hemivertebra at T9 and T10. An echocardiogram showed Tetralogy of Fallot. GTG-banded karyotyping was performed on peripheral blood cells and revealed 46,XX. Zygosity testing established the pair of twins to be monozygotic with a probability greater than 99:1. COMMENT: Goldenhar syndrome was diagnosed in one of the twins described here. There are several reports of twins discordant for this disorder and therefore non-genetic factors may also play an important role, for instance vascular disruption during morphogenesis.OBJETIVO: Relatar um par de gêmeas monozigóticas, no qual uma das crianças é afetada pela síndrome de Goldenhar, enquanto a outra é saudável. DESCRIÇÃO: Paciente do sexo feminino, filha de pais sadios, jovens e não consangüíneos. A propósita nasceu de parto cesáreo pré-termo com Capurro somático de 35 semanas e 2 dias, pesando 2.170 g, com 42,5 cm de comprimento, perímetro cefálico de 30 cm e Apgar 3/7. Ao nascimento, a criança evoluiu com desconforto respiratório grave, sendo transferida para unidade de tratamento intensivo neonatal. A outra gemelar nasceu com 3.200 g, 49 cm de comprimento, 34 cm de perímetro cefálico e Apgar 8/10. Foi transferida junto com a mãe para o alojamento conjunto da maternidade e recebeu alta com 2 dias de vida. A criança afetada apresentava hipoplasia facial esquerda, micrognatia importante, displasia de pavilhão auricular e apêndices pré-auriculares bilaterais e dermóide epibulbar à direita. Evoluiu com apnéia obstrutiva, em conseqüência da micrognatia, e necessitou de traqueostomia. As ultra-sonografias de crânio e abdome foram normais, a radiografia de coluna total mostrou hemivértebra em T9/T10, o ecocardiograma detectou tetralogia de Fallot, e o cariótipo realizado a partir de linfócitos de sangue periférico com bandeamento GTG foi 46,XX. A avaliação oftalmológica foi normal. O exame molecular provou tratar-se de gêmeas monozigóticas com 99,99% de probabilidade. COMENTÁRIO: A clínica e os exames complementares levaram ao diagnóstico de síndrome de Goldenhar. Existem relatos de gemelares afetados por essa condição com expressividade variável, o que corrobora a hipótese de que a etiologia não é puramente genética, mas resultado de um processo de disrupção vascular no período de morfogênese.Centro Universitário Barão de Mauá Faculdade de MedicinaHospital Santa Casa de Misericórdia de Ribeirão PretoUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial

HER2 negative; Ipatasertib; PI3K/AKTHER2 negativo; Ipatasertib; PI3K/AKTHER2 negatiu; Ipatasertib; PI3K/AKTPurpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse < 1 year since (neo)adjuvant chemotherapy were ineligible. Patients were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, plus paclitaxel (80 mg/m2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects.This work was supported by Genentech/Roche. Medical writing assistance was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Utility of early circulating tumour DNA dynamics as a surrogate for progression free survival in the BEECH phase I/II trial in metastatic breast cancer

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A multibiomarker approach in the caged neotropical fish to assess the environment health in a river of central Brazilian Cerrado

Embargo until 19 August 2022.Water safety is a world-wide concern and several efforts have been made in order to ensure the conservation of aquatic ecosystems. Water quality monitoring must be performed with an integrated approach using biomonitor organisms allied to water parameters. Nonetheless, very few studies have focused on biomarker responses in neotropical fish, especially in the freshwater ecosystem of Brazilian Cerrado savanna. In present study, the active biomonitoring of the João Leite river (central Brazilian Cerrado river) was performed through the evaluation of biomarker responses in caged Astyanax lacustris in combination with land use classification and analysis of water parameters. Caged fish were exposed for seven days at four sites along the river and two control groups were kept in a tank under controlled conditions. Results showed that pasture was the predominant land use in the João Leite river basin (54.07%), followed by natural vegetation (34.92%) and other kind of land use (11.01%). Water analyses showed metal concentrations (Mn and Fe) above the maximum allowed by Brazilian regulation, with particularly higher concentrations at Site 2 (near to pasture area). Biomarker responses did not show significant differences for somatic and mutagenic biomarkers between sites. However, the comet assay showed high DNA damage at Sites 2 and 3, indicating genotoxic effects in caged fish at pasture areas. Histopathological analysis showed highest frequency of leukocyte infiltration in liver of fish from Site 2, confirming the ecotoxic effects on A. lacustris in streams impacted by grazing activities. DNA damage and leukocyte infiltration in fish hepatic tissues were sensitive biomarkers in the neotropical fish A. lacustris to assess the environment health of the Cerrado river. These results showed the importance of using a multibiomarker approach in environmental risk assessment, especially in areas more at risk from anthropogenic pollution.acceptedVersio

Perspective on Quantum Bubbles in Microgravity

Progress in understanding quantum systems has been driven by the exploration of the geometry, topology, and dimensionality of ultracold atomic systems. The NASA Cold Atom Laboratory (CAL) aboard the International Space Station has enabled the study of ultracold atomic bubbles, a terrestrially-inaccessible topology. Proof-of-principle bubble experiments have been performed on CAL with an rf-dressing technique; an alternate technique (dual-species interaction-driven bubbles) has also been proposed. Both techniques can drive discovery in the next decade of fundamental physics research in microgravity.Comment: 17 pages, 2 figure

Digital Dance-theatre as a Multidimensional Romance Notes on the production of C8's Flatland

This paper is an account of practice-based research and artistic work carried out by the authors in the field of digital dance theatre (C8’s Flatland). The work addresses the question of body-machine interaction from the point of view of a relationship (or digital romance), involving continuous and discontinuous processes of movement characteristic both to humans and technological machines. The essay explores Andre Leroi-Gourhan’s notion of ‘multidimensional graphism’ to speak of a type of digital writing that does not give prevalence to textual writing, to choreographic writing (or the virtual embodied writing of dance), to visuals, or code, but which functions as an amalgam of all these. We speak to Brian Rotman’a idea of gesturo-haptic language, as a kind of lingua franca that enables machines and bodies to relate to one another as part of the same intercommunictaional transaction, and as part of the same creative process for the emergence, and self-emergence of multidimensional artistic form

Morphodynamical modelling of field-scale swash events

In the present work, data for three single swash events are selected from those available for an accretive tide that occurred at Le Truc Vert beach (France) during a measurement field campaign at that location. These events are primarily chosen because of the different final bed change they produced, namely variable accretion, seaward erosion/landward deposition and variable erosion along the swash zone. These data are compared to results obtained from a ‘state-of-the-art’ numerical fully-coupled 1D morphodynamical shallow water solver, driven by measurements made of those events in the lower swash/inner surf zone. It is found that the hydrodynamics is reasonably well represented, although the computed results exhibit reduced maximum inundations in comparison with the observed ones. The model reproduces the correct order of magnitude of the morphodynamic change after each event, and sometimes the pattern of erosion and deposition, but this change is generally underestimated. Sensitivity analyses are conducted with respect to more uncertain physical parameters and assumed initial conditions. They suggest that initial spatial distributions for velocity and pre-suspended sediment concentration play a key role in the quantitative and qualitative prediction of the bed change

Understanding the Uptown Triangle Neighborhood: Mapping Quality of Life Indicators in the Black Pearl

In the spring of 2015, University of New Orleans (UNO) students enrolled in the MURP 4081/5081 course-Applied Geographic Information Systems: Information Technology for the Planning Profession (also known as ‘Applied GIS’) led by Dr. Michelle Thompson. Since 2008 this course has provided students with a blended experience with learning the theory and receiving an introduction to spatial analysis using the Environmental Systems Research Institute (ESRI) ArcGIS software then applying this knowledge as GIS Analysts with a non-profit community partner. In the fall of 2014, Dr. Thompson competed to have this course designated as the inaugural Department of Planning and Urban Studies (PLUS) service learning course. By January 2015, Thompson developed a scope of services and formed a partnership with the Uptown Triangle Neighborhood Association (UTNA) to evaluate Quality of Life Indicators limited to the evaluation of property, road, and storm drain conditions. The Uptown Triangle Neighborhood (UTN), which was formerly known as the ‘Black Pearl’, is a triangular shaped neighborhood and is bounded by Street Charles Avenue, Broadway Avenue, and Leake Avenue. Prior to the UTNA study, Graham Hayes – UTNA Board Member, UT resident, former WhoData Intern and Bachelor of Science in Urban Studies Program’14 graduate, had developed a series of datasets and crowdsourced data through resident and volunteer activities from spring to early fall 2014. The GIS Mapping Analysts collected primary and integrated secondary data to provide the results of their study in this report. Within the same project, a separate team of novice GIS Programming Analysts developed, tested with the GIS Mapping Analysts and deployed a web-enabled data collection application known as the ‘WhoData Map App.’ The goal of this project and the goal of the client, is to create a tool that will empower members of the neighborhood to advocate community involvement in decision making for the Uptown Triangle Neighborhood. It will also provide a strategic resource for members of the community to evaluate future conditions that may impact the quality of life for those that live there

QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents