1,457 research outputs found

    Molecular area effects in Cepaea

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    Toll-like receptor 9 in breast cancer.

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    Toll-like receptor 9 (TLR9) is a cellular DNA receptor of the innate immune system. DNA recognition via TLR9 results in an inflammatory reaction, which eventually also activates a Th1-biased adaptive immune attack. In addition to cells of the immune system, TLR9 mRNA and protein are also widely expressed in breast cancer cell lines and in clinical breast cancer specimens. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. In the studies conducted so far, tumor TLR9 expression has been shown to have prognostic significance only in patients that have triple-negative breast cancer (TNBC). Specifically, high tumor TLR9 expression predicts good prognosis among TNBC patients. Pre-clinical studies suggest that TLR9 expression may affect tumor immunophenotype and contribute to the immunogenic benefit of chemotherapy. In this review, we discuss the possible contribution of tumor TLR9 to the pathogenesis and treatment responses in breast cancer.</p

    Genetic Polymorphism in Evolving Population

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    We present a model for evolving population which maintains genetic polymorphism. By introducing random mutation in the model population at a constant rate, we observe that the population does not become extinct but survives, keeping diversity in the gene pool under abrupt environmental changes. The model provides reasonable estimates for the proportions of polymorphic and heterozygous loci and for the mutation rate, as observed in nature

    Bootstrap calibration of TRANSMIT for informative missingness of parental genotype data

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    Informative missingness of parental genotype data occurs when the genotype of a parent influences the probability of the parent's genotype data being observed. Informative missingness can occur in a number of plausible ways and can affect both the validity and power of procedures that assume the data are missing at random (MAR). We propose a bootstrap calibration of MAR procedures to account for informative missingness and apply our methodology to refine the approach implemented in the TRANSMIT program. We illustrate this approach by applying it to data on hypertensive probands and their parents who participated in the Framingham Heart Study

    Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A : A nationwide real-world study with 700 person-years

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    AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.Peer reviewe

    Wrasse fishery on the Swedish West Coast: towards ecosystem-based management

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    Fishing and translocation of marine species for use in aquaculture is widespread. Corkwing, goldsinny, and ballan wrasse (Symphodus melops, Ctenolabrus rupestris, and Labrus bergylta) are fished on the Swedish west coast for use as cleaner-fish in Norwegian salmon farms. Here, we aim to provide knowledge and recommendations to support ecosystem-based management for wrasse fisheries in Sweden. We compared fished and non-fished areas to test if current fishery levels have led to stock depletion. To gain insight on the role of wrasse in the algal belt trophic chain, we analysed the gut contents of goldsinny and corkwing using metabarcoding. Finally, we analysed the trophic interactions of wrasse and potential prey in a mesocosm study. We could not detect any signs of stock depletion or altered size structure in fished areas compared to the protected control area. Gut analyses confirmed both goldsinny and corkwing as non-specialized, omnivorous opportunists and revealed, with 189 prey taxa detected, a broader spectrum of prey than previously known. Common prey items included mesoherbivores such as small gastropods and crustaceans, but also insects and algae. We conclude that there are no visible signs of stock depletion at the current removal level of wrasses by the fishery. However, this emerging fishery should be closely monitored for potential cascading effects on the algal belt ecosystem, and our study could provide a baseline for future monitoring
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