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1.
Nat Commun ; 15(1): 3275, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627430

RESUMO

Functional trade-offs can affect patterns of morphological and ecological evolution as well as the magnitude of morphological changes through evolutionary time. Using morpho-functional landscape modelling on the cranium of 132 carnivore species, we focused on the macroevolutionary effects of the trade-off between bite force and bite velocity. Here, we show that rates of evolution in form (morphology) are decoupled from rates of evolution in function. Further, we found theoretical morphologies optimising for velocity to be more diverse, while a much smaller phenotypic space was occupied by shapes optimising force. This pattern of differential representation of different functions in theoretical morphological space was highly correlated with patterns of actual morphological disparity. We hypothesise that many-to-one mapping of cranium shape on function may prevent the detection of direct relationships between form and function. As comparatively only few morphologies optimise bite force, species optimising this function may be less abundant because they are less likely to evolve. This, in turn, may explain why certain clades are less variable than others. Given the ubiquity of functional trade-offs in biological systems, these patterns may be general and may help to explain the unevenness of morphological and functional diversity across the tree of life.


Assuntos
Evolução Biológica , Crânio , Crânio/anatomia & histologia , Força de Mordida , Filogenia
2.
Lancet ; 403(10431): 1061-1070, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38402886

RESUMO

BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Adulto , Humanos , Adolescente , Sunitinibe/uso terapêutico , Feocromocitoma/tratamento farmacológico , Feocromocitoma/etiologia , Intervalo Livre de Progressão , Hipertensão/etiologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/etiologia , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
JCO Precis Oncol ; 7: e2300053, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-38127829

RESUMO

PURPOSE: Medullary thyroid cancer (MTC) harbors frequent mutations in RET oncogene. Selective RET inhibitors (RETi) have emerged as effective treatments. However, resistance almost invariably occurs. METHODS: MTC patients who were initiated on RETi between 2018 and 2022 were included. Baseline characteristics, RET mutational status, RETi response, available tumor tissue and molecular profiles sampled pre- and post-RETi were analyzed. RESULTS: Among 46 MTC patients on RETi during the study period, 26 patients had discontinued at data cut-off because of progression (n = 16), death (n = 4), and toxicity (n = 6). The most frequent RET mutations at baseline were p.M918T (n = 29), and p.C634X (n = 6). Pre- and post-RETi molecular profiles were available in 14 patients. There was no primary resistance on pre-RETi samples. Post-RETi profiles revealed a bypass mechanism of resistance in 75% of the cases including RAS genes mutations (50%), FGFR2 and ALK fusions and and MYC p.P44L. RET solvent from and hinge region mutations was the only resistance mechanisms in 25% of the cases. Tumor samples from initial thyroidectomy, pre- and post-RETi, from six patients, showed an increase of the mean Ki 67-index of 7%, 17% and 40% respectively (P = 0.037) and a more aggressive poorly differentiated histology in three patients. DISCUSSION: Bypass resistance may be the most frequent mechanism of progression under RETi. A more aggressive histology may arise following RETi and warrants further investigation.


Assuntos
Carcinoma Medular , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma Medular/cirurgia , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Inibidores de Proteínas Quinases , Falha de Tratamento , Transfecção
4.
J R Soc Interface ; 20(204): 20230293, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37434502

RESUMO

Many of the world's 10 000 bird species lay coloured or patterned eggs. The large diversity of eggshell patterning among birds, achieved through pigment, has been attributed to a few selective agents such as crypsis, thermoregulation, egg recognition, mate signalling, egg strength and protecting the embryo from UV. Pigmentation may influence the texture of eggshells, which in turn may be important for dealing with water and microbes. We measured surface roughness (Sa, nm), surface skewness (Ssk) and surface kurtosis (Sku), which describe different aspects of surface texture, across 204 bird species with maculated (patterned) eggs and 166 species with immaculate (non-patterned) eggs. Using phylogenetically controlled analyses, we tested whether maculated eggshells have different surface topography between the foreground colour and background colour, and between the background colour of maculated eggshells and the surface of immaculate eggshells. Secondly, we determined to what extent variation in eggshell pigmentation of the foreground and background colour is determined by phylogenetic relatedness, and whether certain life-history traits are important predictors of eggshell surface structure. We show that the surface of maculated eggs consists of a rougher foreground pigment compared to the background pigment across 71% of the 204 bird species (54 families) investigated. Species that lay immaculate eggs showed no difference in surface roughness, kurtosis or skewness compared to background pigment of maculated eggs. The difference in eggshell surface roughness between foreground and background pigmentation was greater among species that occupied dense habitats, such as forests with closed canopies, compared to those that nest in open and semi-open habitats (e.g. cities, deserts, grasslands, open shrubland and seashores). Among maculated eggs, foreground texture was correlated with habitat, parental care, diet, nest location, avian group and nest type, while background texture was correlated with clutch size, annual temperature, development mode and annual precipitation. Surface roughness among immaculate eggs was greatest for herbivores, and species that have larger clutch sizes. Together, this suggests that multiple life-history traits have influenced the evolution of eggshell surface textures in modern birds.


Assuntos
Casca de Ovo , Pigmentação , Animais , Aves , Regulação da Temperatura Corporal , Filogenia
6.
R Soc Open Sci ; 10(5): 221023, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37234505

RESUMO

The eggs of avian obligate brood-parasitic species have multiple adaptations to deceive hosts and optimize development in host nests. While the structure and composition of the eggshell in all birds is essential for embryo growth and protection from external threats, parasitic eggs may face specific challenges such as high microbial loads, rapid laying and ejection by the host parents. We set out to assess whether eggshells of avian brood-parasitic species have either (i) specialized structural properties, to meet the demands of a brood-parasitic strategy or (ii) similar structural properties to eggs of their hosts, due to the similar nest environment. We measured the surface topography (roughness), wettability (how well surfaces repel water) and calcium content of eggshells of a phylogenetically and geographically diverse range of brood-parasitic species (representing four of the seven independent lineages of avian brood-parasitic species), their hosts and close relatives of the parasites. These components of the eggshell structure have been demonstrated previously to influence such factors as the risk of microbial infection and overall shell strength. Within a phylogenetically controlled framework, we found no overall significant differences in eggshell roughness, wettability and calcium content between (i) parasitic and non-parasitic species, or (ii) parasitic species and their hosts. Both the wettability and calcium content of the eggs from brood-parasitic species were not more similar to those of their hosts' eggs than expected by chance. By contrast, the mean surface roughness of the eggs of brood-parasitic species was more similar to that of their hosts' eggs than expected by chance, suggesting brood-parasitic species may have evolved to lay eggs that match the host nest environment for this trait. The lack of significant overall differences between parasitic and non-parasitic species, including hosts, in the traits we measured, suggests that phylogenetic signal, as well as general adaptations to the nest environment and for embryo development, outweigh any influence of a parasitic lifestyle on these eggshell properties.

7.
Clin Cancer Res ; 29(13): 2401-2409, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37074727

RESUMO

PURPOSE: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. PATIENTS AND METHODS: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. RESULTS: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients. CONCLUSIONS: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Tirotropina Alfa , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Radioisótopos do Iodo/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Prospectivos , Piridonas/efeitos adversos , Pirimidinonas , Oximas/efeitos adversos , Adenocarcinoma/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mutação
8.
Gland Surg ; 11(1): 91-99, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242672

RESUMO

BACKGROUND: Intraoperative neuromonitoring (IONM) in thyroid surgery requires electric stimulation of the vagus nerve to verify correct electrode placement. Classically the nerve is found deep to or in-between the common carotid artery and internal jugular vein, but previous studies have shown that the nerve can sometimes be found superficial to the vessels. Our aim was to determine the incidence of a superficial vagus nerve using ultrasound (US) and study possible clinical factors associated with an anteriorly-located vagus nerve. METHODS: Retrospective study of patients undergoing thyroid surgery (lobectomy or total thyroidectomy) with intermittent IONM. Substernal goiters, locally invasive tumors or bulky lymph nodes were excluded. The vagus nerve was identified at the level of the mid-thyroid lobe on each side on preoperative US performed by two specialized radiologists, and its location according to 6 possible positions in relationship to the common carotid artery was recorded. The anatomic variability of the vagus nerve was analyzed in relationship to patient demographics and thyroid pathology. RESULTS: Five-hundred twenty-seven patients were included. The right vagus nerve (n=522) was in-between, superficial or deep to the vessels in 92.3%, 6.1% and 1.5% and of cases, respectively, and the left vagus (n=517) in 80.2%, 18.6% and 1.2% of cases, respectively, with a statistically significant difference between right and left vagus nerves (P<0.001). The type of pathology, size of the dominant nodule or the volume of the thyroid lobe were not correlated to finding a superficial vagus nerve. CONCLUSIONS: The vagus nerve was identified in all cases on US and found to be anterior to common carotid artery at the level of the thyroid lobe in 18.6% of cases on the left and 6.1% of cases on the right. Identifying this anatomic variant preoperatively may facilitate IONM and avoid inadvertent trauma to the vagus nerve during thyroid surgery.

9.
J R Soc Interface ; 18(183): 20210488, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34637642

RESUMO

Complex and at times extreme environments have pushed many bird species to develop unique eggshell surface properties to protect the embryo from external threats. Because microbes are usually transmitted into eggs by moisture, some species have evolved hydrophobic shell surfaces that resist water absorption, while also regulating heat loss and the exchange of gases. Here, we investigate the relationship between the wettability of eggshells from 441 bird species and their life-history traits. We measured the initial contact angle between sessile water droplets and the shell surface, and how far the droplet spread. Using phylogenetic comparative methods, we show that body mass, annual temperature and eggshell maculation primarily explained variance in water contact angle across eggshells. Species nesting in warm climates were more likely to exhibit highly hydrophobic eggshells than those nesting in cold climates, potentially to reduce microbial colonization. In non-passerines, immaculate eggs were found to have more hydrophobic surfaces than maculate eggshells. Droplets spread more quickly on eggshells incubated in open nests compared to domed nests, likely to decrease heat transfer from the egg. Here, we identify clear adaptations of eggshell wettability across a diverse range of nesting environments, driven by the need to retain heat and prevent microbial adhesion.


Assuntos
Aves , Casca de Ovo , Animais , Filogenia , Água , Molhabilidade
10.
Proc Biol Sci ; 288(1953): 20210823, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34130502

RESUMO

Embryo survival in birds depends on a controlled transfer of water vapour and respiratory gases through the eggshell, and this exchange is critically sensitive to the surrounding physical environment. As birds breed in most terrestrial habitats worldwide, we proposed that variation in eggshell conductance has evolved to optimize embryonic development under different breeding conditions. This is the first study to take a broad-scale macro-ecological view of avian eggshell conductance, encompassing all key avian taxonomic groups, to assess how life history and climate influence the evolution of this trait. Using whole eggs spanning a wide phylogenetic diversity of birds, we determine that body mass, temperature seasonality and whether both parents attend the nest are the main determinants of eggshell conductance. Birds breeding at high latitudes, where seasonal temperature fluctuations are greatest, will benefit from lower eggshell conductance to combat temporary periods of suspended embryo growth and prevent dehydration during prolonged incubation. The nest microclimate is more consistent in species where parents take turns incubating their clutch, resulting in lower eggshell conductance. This study highlights the remarkable functional qualities of eggshells and their importance for embryo survival in extreme climates.


Assuntos
Casca de Ovo , Comportamento de Nidação , Animais , Aves , Clima , Filogenia
11.
Eur J Endocrinol ; 185(1): 13-22, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33886499

RESUMO

OBJECTIVE: The presence of extrathyroidal extension (ETE) is generally considered as an indication for total thyroidectomy for differentiated thyroid cancer. The accuracy of neck ultrasound for the diagnosis of ETE is controversial. The aim of this study was to assess the diagnostic accuracy of preoperative ultrasound evaluation of ETE. METHODS: The retrospective and observational study of consecutive patients operated between 2016 and 2019 for cytologically suspicious or indeterminate thyroid nodules were analyzed. US images obtained preoperatively were retrospectively reviewed to identify signs of minimal or gross ETE. Histology was considered as the golden standard for diagnosis of ETE. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of US were evaluated. RESULTS: A cohort of 305 patients (75% females, median age 48 years) with 378 nodules (median size 18 mm) was studied. Seventy-five percent of the nodules (n = 228) were malignant on histology and ETE was present in 106 cases (28%): 83 minimal ETE and 23 gross ETE. Suspicion of minimal ETE on preoperative ultrasound was found in 50 (13%) with a sensitivity of 30%, a specificity of 93%, a PPV of 62% and an NPV of 78%, with an accuracy of 76%. Gross ETE on ultrasound was found in 19 (5%) nodules with a sensitivity of 78%, a specificity of 99.7% a PPV of 94.7% an NPV of 98.6% and an accuracy of 98%. CONCLUSIONS: Preoperative US is very specific and accurate in diagnosing gross ETE which impacts the extent of initial surgery for thyroid cancers.


Assuntos
Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Invasividade Neoplásica , Estudos Retrospectivos , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
12.
Endocr Relat Cancer ; 28(1): 15-26, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112817

RESUMO

Anaplastic thyroid cancer (ATC) is a rare lethal disease. Lenvatinib is an off-label therapeutic option for ATC in most countries, except in Japan. The aim of this multicenter retrospective survey was to analyze the efficacy and the toxicity profile of off-label lenvatinib treatment in all adults advanced ATC patients, in France. Of the 23 patients analysed (14 males; mean age 64 years), 15 were pure ATC and 8 were mixed tumors (i.e. with a differentiated or poorly differentiated component). Prior treatments included neck external beam irradiation in 74%, at least one line of chemotherapy in 22 cases, two lines of chemotherapy in 11 patients, other TKI in 4 cases. A central RECIST assessment was performed. Since lenvatinib initiation, median PFS was 2.7 months (95% CI; 1.9-3.5) and median OS was 3.1 months (95% CI; 0.6-5.5). OS was significantly longer in case of mixed tumors compared with pure ATC (6.3 vs 2.7 months, P = 0.026). Best tumor response was partial response in two cases and stable disease in seven. Clinical improvement was achieved in seven patients. Lethal adverse events occurred in three patients, consisting in haemoptysis in two cases and pneumothorax in one case. Among long-surviving ATC patients (>6 months), four underwent biopsy of distant metastasis, revealing poorly differentiated histology; three of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure vs mixed ATC disclose differences in disease aggressiveness and treatment response. Long-surviving ATC patients might benefit from biopsy of persistent disease, searching for histological transition or molecular target.


Assuntos
Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia
14.
Sci Rep ; 9(1): 7076, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068662

RESUMO

Most birds of prey (raptors), rely heavily on their talons for capturing prey. However, the relationship between talon shape and the ability to take prey is poorly understood. In this study we investigate whether raptor talons have evolved primarily in response to adaptive pressures exerted by different dietary demands, or if talon morphology is largely constrained by allometric or phylogenetic factors. We focus on the hallux talon and include 21 species in total varying greatly in body mass and feeding ecology, ranging from active predation on relatively large prey to obligate scavenging. To quantify the variation in talon shape and biomechanical performance within a phylogenetic framework, we combined three dimensional (3D) geometric morphometrics, finite element modelling and phylogenetic comparative methods. Our results indicate that relative prey size plays a key role in shaping the raptorial talon. Species that hunt larger prey are characterised by both distinct talon shape and mechanical performance when compared to species that predate smaller prey, even when accounting for phylogeny. In contrast to previous results of skull-based analysis, allometry had no significant effect. In conclusion, we found that raptor talon evolution has been strongly influenced by relative prey size, but not allometry and, that talon shape and mechanical performance are good indicators of feeding ecology.


Assuntos
Tamanho Corporal/fisiologia , Casco e Garras/fisiologia , Comportamento Predatório/fisiologia , Aves Predatórias/fisiologia , Animais , Evolução Biológica , Fenômenos Biomecânicos , Dieta , Casco e Garras/diagnóstico por imagem , Filogenia , Aves Predatórias/classificação , Microtomografia por Raio-X
15.
Thyroid ; 29(5): 735-742, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30880598

RESUMO

A 59-year-old woman with locally invasive poorly differentiated thyroid cancer with synchronous lung, mediastinal, and bone metastases and a somatic BRAFK601E mutation with contraindication for antiangiogenic drugs was treated with dabrafenib and trametinib. During treatment, serum levels of thyroglobulin increased as early as day 7 up to 10-fold over baseline at week 4. Concurrently, clinical hyperthyroidism occurred, with free triiodothyronine and free thyroxine levels increasing to 6.6 and 4.4 times their upper reference limit. Fludeoxyglucose positron emission tomography/computed tomography at one and two months after treatment initiation showed a PERCIST metabolic response with a 82% decrease in fludeoxyglucose uptake, whereas disease remained morphologically stable according to RECIST criteria. A diagnostic radioactive iodine whole-body scan performed when the patient was thyrotoxic with an undetectable serum thyrotropin level, in the absence of any exogenous thyrotropin stimulation, showed high radioactive iodine uptake in the lung, mediastinum, and skull metastases. A biopsy performed two months after treatment initiation showed a more differentiated growth pattern and a decrease in the mitotic activity compared to baseline. An increase of thyroglobulin and thyroid peroxidase was observed at both the protein and mRNA levels. Sodium-iodide symporter mRNA expression increased by >750 times over its initial level, and sodium-iodide symporter protein expression became detectable under treatment. A decrease in general status due to thyrotoxicosis led to treatment discontinuation. Thyrotoxicosis resolved rapidly and radioactive iodine uptake decreased by >90%. This clinical case shows that redifferentiation itself is not necessarily associated with an antitumor effect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/administração & dosagem , Mutação , Oximas/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias da Glândula Tireoide/patologia , Diferenciação Celular , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética
16.
Eur J Cancer ; 103: 137-142, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30223227

RESUMO

We evaluated the impact of patient-assisted compression (PAC) on image quality, dose, workflow and patient experience of mammography. Patients aged 40-90 years coming for bilateral mammography were included prospectively in the study. After positioning each breast, the technologist performed the compression and exposure of the first breast, initiated the compression of the other until 3 daN and then let the patient complete the compression using a remote control device. Image quality, compression force, breast thickness, average glandular dose and pain value for each breast were assessed for PAC and technologist compression (TC). The compression level was significantly higher with PAC than TC for both craniocaudal (CC; median difference 2.0 daN, p < 0.0001) and mediolateral oblique (MLO) views (median difference 1.5 daN, p < 0.0001). Breast thickness was reduced with PAC (CC, median difference -1.90 cm, p = 0.02), as well as glandular dose (CC, median difference -0.03, p = 0.02). The image quality was rated equivalent for both modes in 85% (85/100) of cases, superior for PAC in 10% (10/100) of cases and inferior in 5% (5/100) of cases. There was no significant difference in discomfort or pain felt between PAC and TC modes. Seventy-four percent of patients reported that the self-compressing device would facilitate their reattendance. PAC may be a suitable technique for mammography examinations, providing an equivalent image quality to TC. Moreover, as the breast compression level is increased, PAC may help reduce breast thickness, hence glandular dose. The fact that patients have control over the procedure may change their perception of mammography and improve uptake and compliance.


Assuntos
Mama/diagnóstico por imagem , Aumento da Imagem/métodos , Mamografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Pressão , Autocuidado/métodos
17.
PeerJ ; 6: e5052, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967731

RESUMO

This paper proposes a new methodology to quantify patterns of egg shape variation using geometric morphometrics of three-dimensional landmarks captured on digitally reconstructed eggshells and demonstrates its performance in capturing shape variation at multiple biological levels. This methodology offers unique benefits to complement established linear measurement or two-dimensional (2D) contour profiling techniques by (i) providing a more precise representation of eggshell curvature by accounting for variation across the entire surface of the egg; (ii) avoids the occurrence of correlations from combining multiple egg shape features; (iii) avoids error stemming from projecting a highly-curved three-dimensional (3D) object into 2D space; and (iv) enables integration into 3D workflows such as finite elements analysis. To demonstrate, we quantify patterns of egg shape variation and estimate morphological disparity at multiple biological levels, within and between clutches and among species of four passerine species of different lineages, using volumetric dataset obtained from micro computed tomography. The results indicate that species broadly have differently shaped eggs, but with extensive within-species variation so that all four-focal species occupy a range of shapes. Within-species variation is attributed to between-clutch differences in egg shape; within-clutch variation is surprisingly substantial. Recent comparative analyses that aim to explain shape variation among avian taxa have largely ignored potential biases due to within-species variation, or use methods limited to a narrow range of egg shapes. Through our approach, we suggest that there is appreciable variation in egg shape across clutches and that this variation needs to be accounted for in future research. The approach developed in this study to assess variation in shape is freely accessible and can be applied to any spherical-to-conical shaped object, including eggs of non-avian dinosaurs and reptiles through to other extant taxa such as poultry.

18.
Proc Biol Sci ; 283(1822)2016 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-26763698

RESUMO

The moa (Dinornithiformes) are large to gigantic extinct terrestrial birds of New Zealand. Knowledge about niche partitioning, feeding mode and preference among moa species is limited, hampering palaeoecological reconstruction and evaluation of the impacts of their extinction on remnant native biota, or the viability of exotic species as proposed ecological 'surrogates'. Here we apply three-dimensional finite-element analysis to compare the biomechanical performance of skulls from five of the six moa genera, and two extant ratites, to predict the range of moa feeding behaviours relative to each other and to living relatives. Mechanical performance during biting was compared using simulations of the birds clipping twigs based on muscle reconstruction of mummified moa remains. Other simulated food acquisition strategies included lateral shaking, pullback and dorsoventral movement of the skull. We found evidence for limited overlap in biomechanical performance between the extant emu (Dromaius novaehollandiae) and extinct upland moa (Megalapteryx didinus) based on similarities in mandibular stress distribution in two loading cases, but overall our findings suggest that moa species exploited their habitats in different ways, relative to both each other and extant ratites. The broad range of feeding strategies used by moa, as inferred from interspecific differences in biomechanical performance of the skull, provides insight into mechanisms that facilitated high diversities of these avian herbivores in prehistoric New Zealand.


Assuntos
Aves/fisiologia , Herbivoria , Crânio/fisiologia , Animais , Fenômenos Biomecânicos , Extinção Biológica , Fósseis , Imageamento Tridimensional , Nova Zelândia , Crânio/anatomia & histologia , Especificidade da Espécie
19.
PLoS One ; 9(4): e93088, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24718109

RESUMO

Thylacinidae is an extinct family of Australian and New Guinean marsupial carnivores, comprizing 12 known species, the oldest of which are late Oligocene (∼24 Ma) in age. Except for the recently extinct thylacine (Thylacinus cynocephalus), most are known from fragmentary craniodental material only, limiting the scope of biomechanical and ecological studies. However, a particularly well-preserved skull of the fossil species Nimbacinus dicksoni, has been recovered from middle Miocene (∼16-11.6 Ma) deposits in the Riversleigh World Heritage Area, northwestern Queensland. Here, we ask whether N. dicksoni was more similar to its recently extinct relative or to several large living marsupials in a key aspect of feeding ecology, i.e., was N. dicksoni a relatively small or large prey specialist. To address this question we have digitally reconstructed its skull and applied three-dimensional Finite Element Analysis to compare its mechanical performance with that of three extant marsupial carnivores and T. cynocephalus. Under loadings adjusted for differences in size that simulated forces generated by both jaw closing musculature and struggling prey, we found that stress distributions and magnitudes in the skull of N. dicksoni were more similar to those of the living spotted-tailed quoll (Dasyurus maculatus) than to its recently extinct relative. Considering the Finite Element Analysis results and dental morphology, we predict that N. dicksoni likely occupied a broadly similar ecological niche to that of D. maculatus, and was likely capable of hunting vertebrate prey that may have exceeded its own body mass.


Assuntos
Tamanho Corporal , Processamento de Imagem Assistida por Computador , Marsupiais/fisiologia , Comportamento Predatório/fisiologia , Animais , Fenômenos Biomecânicos , Peso Corporal , Mastigação , Músculos/fisiologia , Análise de Componente Principal , Estresse Mecânico , Fatores de Tempo
20.
PLoS One ; 8(12): e82261, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367509

RESUMO

The description of a Neanderthal hyoid from Kebara Cave (Israel) in 1989 fuelled scientific debate on the evolution of speech and complex language. Gross anatomy of the Kebara 2 hyoid differs little from that of modern humans. However, whether Homo neanderthalensis could use speech or complex language remains controversial. Similarity in overall shape does not necessarily demonstrate that the Kebara 2 hyoid was used in the same way as that of Homo sapiens. The mechanical performance of whole bones is partly controlled by internal trabecular geometries, regulated by bone-remodelling in response to the forces applied. Here we show that the Neanderthal and modern human hyoids also present very similar internal architectures and micro-biomechanical behaviours. Our study incorporates detailed analysis of histology, meticulous reconstruction of musculature, and computational biomechanical analysis with models incorporating internal micro-geometry. Because internal architecture reflects the loadings to which a bone is routinely subjected, our findings are consistent with a capacity for speech in the Neanderthals.


Assuntos
Osso Hioide , Animais , Fenômenos Biomecânicos , Humanos , Homem de Neandertal
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