29 research outputs found

    Skeleton of an unusual cat-sized marsupial relative (Metatheria: Marsupialiformes) from the middle Eocene (Lutetian: 44-43 million years ago) of Turkey

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    We describe a near-complete, three-dimensionally preserved skeleton of a metatherian (relative of modern marsupials) from the middle Eocene (Lutetian: 44–43 million years ago) Lülük member of the Uzunçarşıdere Formation, central Turkey. With an estimated body mass of 3–4 kg, about the size of a domestic cat (Felis catus) or spotted quoll (Dasyurus maculatus), it is an order of magnitude larger than the largest fossil metatherians previously known from the Cenozoic of the northern hemisphere. This new taxon is characterised by large, broad third premolars that probably represent adaptations for hard object feeding (durophagy), and its craniodental morphology suggests the capacity to generate high bite forces. Qualitative and quantitative functional analyses of its postcranial skeleton indicate that it was probably scansorial and relatively agile, perhaps broadly similar in locomotor mode to the spotted quoll, but with a greater capacity for climbing and grasping. Bayesian phylogenetic analysis of a total evidence dataset comprising 259 morphological characters and 9kb of DNA sequence data from five nuclear protein-coding genes, using both undated and “tip-and-node dating” approaches, place the new taxon outside the marsupial crown-clade, but within the clade Marsupialiformes. It demonstrates that at least one metatherian lineage evolved to occupy the small-medium, meso- or hypo-carnivore niche in the northern hemisphere during the early Cenozoic, at a time when there were numerous eutherians (placentals and their fossil relatives) filling similar niches. However, the known mammal fauna from Uzunçarşıdere Formation appears highly endemic, and geological evidence suggests that this region of Turkey was an island for at least part of the early Cenozoic, and so the new taxon may have evolved in isolation from potential eutherian competitors. Nevertheless, the new taxon reveals previously unsuspected ecomorphological disparity among northern hemisphere metatherians during the first half of the Cenozoic

    Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

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    BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

    Cervicale hernia veroorzaakt door het werk?

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    Flat Feet, Happy Feet? Comparison of the Dynamic Plantar Pressure Distribution and Static Medial Foot Geometry between Malawian and Dutch Adults

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    Contains fulltext : 118438.pdf (publisher's version ) (Open Access)In contrast to western countries, foot complaints are rare in Africa. This is remarkable, as many African adults walk many hours each day, often barefoot or with worn-out shoes. The reason why Africans can withstand such loading without developing foot complaints might be related to the way the foot is loaded. Therefore, static foot geometry and dynamic plantar pressure distribution of 77 adults from Malawi were compared to 77 adults from the Netherlands. None of the subjects had a history of foot complaints. The plantar pressure pattern as well as the Arch Index (AI) and the trajectory of the center of pressure during the stance phase were calculated and compared between both groups. Standardized pictures were taken from the feet to assess the height of the Medial Longitudinal Arch (MLA). We found that Malawian adults: (1) loaded the midfoot for a longer and the forefoot for a shorter period during roll off, (2) had significantly lower plantar pressures under the heel and a part of the forefoot, and (3) had a larger AI and a lower MLA compared to the Dutch. These findings demonstrate that differences in static foot geometry, foot loading, and roll off technique exist between the two groups. The advantage of the foot loading pattern as shown by the Malawian group is that the plantar pressure is distributed more equally over the foot. This might prevent foot complaints

    Análise do arco longitudinal medial em adolescentes usuárias de calçados de salto alto Analysis of the medial longitudinal arch in adolescents users of high heeled shoes

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    O objetivo do estudo foi analisar a influência do calçado de salto alto no arco longitudinal medial (ALM) do pé de adolescentes. Fizeram parte do estudo 82 adolescentes entre 13 e 20 anos, sendo 54 não usuárias (grupo controle - GC) e 28 usuárias (grupo experimental - GE) de calçado de salto alto. Foram obtidas as impressões plantares de ambos os pés para análise do ALM, antes e depois do uso de um calçado de salto alto padronizado por um período de 30 minutos. As impressões plantares foram avaliadas pelo índice de Chippaux-Smirak (ICS) e pelo arco de Cavanagh & Rodgers (ICR). O teste de Shapiro-Wilks foi utilizado para a verificação da normalidade dos dados. Variáveis paramétricas pareadas foram tratadas com o Teste t de Student pareado e as não-paramétricas com o teste de Wilcoxon. As comparações não-pareadas foram realizadas com o teste t de Student para as variáveis paramétricas e o de Mann-Withney para as não-paramétricas, com nível de significância de 0,05. Houve diferença no ALM entre os lados direito e esquerdo apenas no GC antes do uso do calçado. Na comparação entre antes e depois do uso do sapato, notou-se diferença apenas no pé esquerdo do GC pelo ICS. Já entre GC e GE, não houve diferença. Apesar dos resultados não evidenciarem alterações no ALM, deve-se lembrar que esta é uma medida estática, sendo necessários estudos do componente dinâmico e do uso do calçado de salto crônico para correlacionar com os achados deste trabalho.<br>The aim of this study was to analyze the influence of high heeled shoes in foot´s medial longitudinal arch in adolescents. Eighty two female adolescents between 13 and 20 years old participated, being 54 non-users of high heleed shoes (control group - GC) and 28 usuaries (experimental group - GE). The footprints of both feet were collected to analyse the medial longitudinal arch (ALM), before and after 30 minutes using a shoe with heel high given by the examiner, an then evaluated by Chippaux-Smirak index (ICS) and Cavanagh & Rodgers Arch index (ICR). The Shapiro-Wilks test was performed to evaluate data normality. For paired comparisons, paired Student's t-test was used in case of parametric data, and the Wilcoxon test in non-parametric data. In non-paired comparisons was used the Student's t-test and the Mann-Whitney test with a level of significance of 0.05. There was a difference between right and left only in CG before the use of the shoe given by the examiner. Comparing before and after the use of this shoe, a difference was noticed only on left foot in CG by ICS. There wasn't any significative difference between CG and EG. Although the results haven´t shown changes in ALM, it must be remembered this is only a static measure, being necessary studies of the dinamic component and the chronic use of high heeled shoes to correlate with the findings of this work
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