89 research outputs found

    Sexual signalling in an artificial population: When does the handicap principle work?

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    Males may use sexual displays to signal their quality to females; the handicap principle provides a mechanism that could enforce honesty in such cases. Iwasa et al. model the signalling of inherited male quality, and distinguish between three variants of the handicap principle: pure epistasis, conditional, and revealing They argue that only the second and third will work. An evolutionary simulation is presented in which all three variants function under certain conditions; the assumptions made by Iwasa et al. are questioned

    Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model

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    Back pain is the leading cause of disability with half of cases attributed to intervertebral disc (IVD) degeneration, yet currently no therapies target this cause. We previously reported an ex vivo caprine loaded disc culture system (LDCS) that accurately represents the cellular phenotype and biomechanical environment of human IVD degeneration. Here, the efficacy of an injectable hydrogel system (LAPONITE® crosslinked pNIPAM-co-DMAc, (NPgel)) to halt or reverse the catabolic processes of IVD degeneration was investigated within the LDCS. Following enzymatic induction of degeneration using 1 mg mL−1 collagenase and 2 U mL−1 chondroitinase ABC within the LDCS for 7 days, IVDs were injected with NPgel alone or with encapsulated human bone marrow progenitor cells (BMPCs). Un-injected caprine discs served as degenerate controls. IVDs were cultured for a further 21 days within the LDCS. Tissues were then processed for histology and immunohistochemistry. No extrusion of NPgel was observed during culture. A significant decrease in histological grade of degeneration was seen in both IVDs injected with NPgel alone and NPgel seeded with BMPCs, compared to un-injected controls. Fissures within degenerate tissue were filled by NPgel and there was evidence of native cell migration into injected NPgel. The expression of healthy NP matrix markers (collagen type II and aggrecan) was increased, whereas the expression of catabolic proteins (MMP3, ADAMTS4, IL-1β and IL-8) was decreased in NPgel (±BMPCs) injected discs, compared to degenerate controls. This demonstrates that NPgel promotes new matrix production at the same time as halting the degenerative cascade within a physiologically relevant testing platform. This highlights the potential of NPgel as a future therapy for IVD degeneration

    Palaeontology, the biogeohistory of Victoria

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    The broad-scale distribution of fossils within Victoria is controlled by general global patterns in the biological evolution of life on Earth, the local development and environmental evolution of habitats, and the occurrence of geological processes conducive to the preservation of fossil floras and faunas. Early Palaeozoic fossils are mostly marine in origin because of the predominance of marine sedimentary rocks in Victoria and because life on land was not significant during most of this time interval. Middle Palaeozoic sequences have both terrestrial and marine fossil records. Within Victoria, marine rocks are only very minor components of strata deposited during the late Palaeozoic, so that few marine fossils are known from this time period. A similar situation existed during most of the Mesozoic except towards the end of this era when marine conditions began to prevail in the Bass Strait region. During long intervals in the Cainozoic, large areas of Victoria were flooded by shallow-marine seas, particularly in the southern basins of Bass Strait, as well as in the northwest of the State (Murray Basin). Cainozoic sediments contain an extraordinary range of animal and plant fossils. During the Quaternary, the landscape of Victoria became, and continues to be, dominated by continental environments including, at times, extensive freshwater lake systems. Fossil floras and faunas from sediments deposited in these lake systems and from other continental sediments, as well as from Quaternary sediments deposited in marginal marine environments, collectively record a history of rapid fluctuations in climate and sea level.<br /

    Clinical Significance of Circulating Tumor Cells in Hormone Receptor–positive Metastatic Breast Cancer Patients who Received Letrozole with or without Bevacizumab

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    Purpose: We evaluated the prognostic and predictive value of circulating tumor cells (CTCs) hormone receptor–positive (HRþ) metastatic breast cancer (MBC) patients randomized to letrozole alone or letrozole plus bevacizumab in the first-line setting (CALGB 40503). Experimental Design: Blood samples were collected at pretreatment and three additional time points during therapy. The presence of ≥5 CTCs per 7.5 mL of blood was considered CTC positive. Association of CTCs with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. Results: Of 343 patients treated, 294 had CTC data and were included in this analysis. Median follow-up was 39 months. In multivariable analysis, CTC-positive patients at baseline (31%) had significantly reduced PFS [HR, 1.49; 95% confidence interval (CI), 1.12–1.97] and OS (HR, 2.08; 95% CI, 1.49–2.93) compared with CTC negative. Failure to clear CTCs during treatment was associated with significantly increased risk of progression (HR, 2.2; 95% CI, 1.58–3.07) and death (HR, 3.4; 95% CI, 2.36–4.88). CTC-positive patients who received only letrozole had the worse PFS (HR, 2.3; 95% CI, 1.54–3.47) and OS (HR, 2.6; 95% CI, 1.59–4.40). Median PFS in CTC-positive patients was significantly longer (18.0 vs. 7.0 months) in letrozole plus bevacizumab versus letrozole arm (P ¼ 0.0009). Restricted mean survival time analysis further revealed that addition of bevacizumab was associated with PFS benefit in both CTC-positive and CTC-negative patients, but OS benefit was only observed in CTC-positive patients. Conclusions: CTCs were highly prognostic for the addition of bevacizumab to first-line letrozole in patients with HRþ MBC in CALGB 40503. Further research to determine the potential predictive value of CTCs in this setting is warranted

    The Williams Scale of Attitude toward Paganism: development and application among British Pagans

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    This article builds on the tradition of attitudinal measures of religiosity established by Leslie Francis and colleagues with the Francis Scale of Attitude toward Christianity (and reflected in the Sahin-Francis Scale of Attitude toward Islam, the Katz-Francis Scale of Attitude toward Judaism, and the Santosh-Francis Scale of Attitude toward Hinduism) by introducing a new measure to assess the attitudinal disposition of Pagans. A battery of items was completed by 75 members of a Pagan Summer Camp. These items were reduced to produce a 21-item scale that measured aspects of Paganism concerned with: the God/Goddess, worshipping, prayer, and coven. The scale recorded an alpha coefficient of 0.93. Construct validity of the Williams Scale of Attitude toward Paganism was demonstrated by the clear association with measures of participation in private rituals

    Measurement of Branching Ratios for Ρc\eta_c Hadronic Decays

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    In a sample of 58 million J/ψJ/\psi events collected with the BES II detector, the process J/ψ→γηc\psi\to\gamma\eta_c is observed in five decay channels: ηc→K+K−π+π−\eta_c \to K^+K^-\pi^+\pi^-, π+π−π+π−\pi^+\pi^-\pi^+\pi^-, K±KS0π∓K^\pm K^0_S \pi^\mp (with KS0→π+π−K^0_S\to\pi^+\pi^-), ϕϕ\phi\phi (with ϕ→K+K−\phi\to K^+K^-) and ppˉp\bar{p}. From these signals, we determine Br(J/ψ→γηc)×Br(ηc→K+K−π+π−)Br(J/\psi\to\gamma\eta_c)\times Br(\eta_c\to K^+K^-\pi^+\pi^-) =(1.5±0.2±0.2)×10−4=(1.5\pm0.2\pm0.2)\times10^{-4}, Br(J/ψ→γηc)×Br(ηc→π+π−π+π−)Br(J/\psi\to\gamma\eta_c)\times Br(\eta_c\to \pi^+\pi^-\pi^+\pi^-) =(1.3±0.2±0.4)×10−4=(1.3\pm0.2\pm0.4)\times10^{-4}, Br(J/ψ→γηc)×Br(ηc→K±KS0π∓)Br(J/\psi\to\gamma\eta_c)\times Br(\eta_c\to K^\pm K_{S}^{0}\pi^\mp) =(2.2±0.3±0.5)×10−4=(2.2\pm0.3\pm0.5)\times10^{-4}, Br(J/ψ→γηc)×Br(ηc→ϕϕ)Br(J/\psi\to\gamma\eta_c)\times Br(\eta_c\to \phi\phi) =(3.3±0.6±0.6)×10−5=(3.3\pm0.6\pm0.6)\times10^{-5} and Br(J/ψ→γηc)×Br(ηc→ppˉ)Br(J/\psi\to\gamma\eta_c)\times Br(\eta_c\to p\bar{p}) =(1.9±0.3±0.3)×10−5=(1.9\pm0.3\pm0.3)\times10^{-5}.Comment: 8 pages, 1 figures and 4 table. Submitted to Phys. Lett.

    Serial Analysis of Circulating Tumor Cells in Metastatic Breast Cancer Receiving First-Line Chemotherapy

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    BACKGROUND: We examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy. METHODS: Serial CTC data from 469 patients (2202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs, combined CTC status at baseline to the end of cycle 1, and tCTC. Akaike information criterion was used to select the model that best predicted PFS and OS. RESULTS: Latent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (56.9% ), low (23.7%), intermediate (14.5%), or high (4.9%). Patients with low, intermediate, and high tCTC patterns had statistically significant inferior PFS and OS compared with those with undetectable CTCs (P < .001). Akaike Information Criterion indicated that the tCTC model best predicted PFS and OS compared with baseline CTCs and combined CTC status at baseline to the end of cycle 1 models. Validation studies in an independent cohort of 1856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model. CONCLUSIONS: We identified 4 novel prognostic groups in MBC based on similarities in tCTC patterns during chemotherapy. Prognostic groups included patients with very poor outcome (intermediate + high CTCs, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be used for fine-tuning of CTC-based risk stratification strategies to guide future prospective clinical trials in MBC

    Track D Social Science, Human Rights and Political Science

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd
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