Estimating Waterfowl Densities in a Flooded Forest: a Comparison of Methods

During winter, aerial surveys are used to estimate densities of ducks that occupy open-water habitats. However, such surveys are ineffective for sampling forest-dwelling species, especially Aix sponsa (Wood Ducks), Anas platyrhynchos (Mallards), and Lophodytes cucullatus (Hooded Mergansers). We evaluated fixed-radius plot (FRP) and Reynolds and Goodrum variable-radius plot (VRP) methods for estimating waterfowl densities in a flooded hardwood bottomland. We constructed 15 elevated blinds on the Angelina River flood plain in eastern Texas and established a 1-ha FRP around each blind; color-coded markers were placed at fixed intervals from each blind. Observers surveyed waterfowl from blinds for 21 mornings during January–March, 1990. For FRPs, species, sex, and time a bird entered and exited the plot were recorded. For VRPs, similar data and estimated observer-to-bird distance were recorded. Data were arranged in a randomized block design and tested using 1-way analyses of variances. Wood Ducks, Mallards, and Hooded Mergansers comprised 68, 18, and 10% of the birds recorded, respectively. Wood Duck density estimates (per ha) for FRP, Reynolds VRP, and Goodrum VRP methods were 0.65, 0.49, and 1.00 (P \u3c 0.001), respectively; for Mallards, estimates were 0.27, 0.20, and 0.33 (P \u3c 0.001), respectively; and estimates were 0.09, 0.13, and 0.15 (P = 0.003) for Hooded Mergansers, respectively. Based on ease of implementation, complexity of data analyses, and precision of density estimates, the FRP and Goodrum VRP methods are recommended for sampling waterfowl in flooded forests

Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure

Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were licensed, creating optimal market conditions and choice for prescribers. FN affects up to 117 per 1000 cancer patients, with mortality rates in the range of 2–21%. By reducing FN incidence and improving chemotherapy relative dose intensity (RDI), G-CSF has been associated with a 3.2% absolute survival benefit. Guidelines recommend primary prophylaxis and that filgrastim be administered for 10–14 days, while pegfilgrastim is administered once per cycle. When taken according to the guidelines, pegfilgrastim and filgrastim are equally effective. However, in routine clinical practice, filgrastim is often under-dosed (< 7 days) and has been shown to be inferior to pegfilgrastim at reducing FN incidence, hospitalisations and maintaining RDI. Once-per-cycle administration with pegfilgrastim might also aid patient adherence. The introduction of biosimilar pegfilgrastim should instigate a rethink of neutropenia management. Biosimilar pegfilgrastim

Multiple equilibria in Tullock contests

We find the sufficient conditions for the existence of multiple equilibria in Tullock-type contests, and show that asymmetric equilibria arise even under symmetric prize and cost structures. We then present existing contests where multiple equilibria exist under reasonably weak conditions

The changing landscape of biosimilars in rheumatology

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities in access to therapy based on economic differences across countries. Since approved biosimilars have already demonstrated highly similar efficacy, it will be most important to establish pharmacovigilance databases across countries that are adequate to monitor long-term safety after marketing approval

Capturing the holistic value of biosimilars in Europe–part 1:a historical perspective

Introduction: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics. Methods: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets. Key insights were also sought from an expert panel of European stakeholders. Results: Survey respondents were clinicians, pharmacists, and payers from Europe (N = 103). Perceived benefits of biosimilars included increased access to innovative medicines (73% of respondents) or biologic treatments (66%). Biosimilar competition was thought to expand access to biologics (~50% of respondents) or drug combinations (~36%) and reduce biologic access time (34%). Key drivers of biologic access after biosimilar competition included increased biologic awareness (51%) and changes to prescribing guidelines (37%) and/or treatment paradigms (28%). The expert panel developed a market maturity framework of biosimilar adoption/opportunities comprising three stages: ‘Invest,’ ‘Expand,’ and ‘Harvest.’ Findings were supported by published literature. Conclusions: In Europe, the perceptions of well-informed survey/interview respondents are that biosimilars have improved patient outcomes via increased access to biologics and innovative biologic products, contributing to earlier and longer treatment of a broader population.</p

Leveraging the holistic benefits of biosimilars in Europe - part 2:how payers can safeguard the future of a healthy biosimilar market environment

IntroductionBiosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets.Areas coveredAn expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1). Directional recommendations are provided for payers.Expert OpinionThe panel's market maturity framework for biosimilars has three stages: 'Invest,' 'Expand' and 'Harvest.' Across market stages, re-thinking the benefits of biosimilars beyond cost-savings, considering earlier or expanded access/new indications, product innovations, and re-investment of biosimilar-generated cost-savings should be communicated to stakeholders to promote further engagement. During 'Expand' and 'Harvest' stages, development of efficient, forward-looking procurement systems and mechanisms that drive uptake and stabilize competition between manufacturers are key. Future biosimilars will target various therapy areas beyond those targeted by existing biosimilars. To ensure a healthy, accessible future market, stakeholders must align their objectives, communicate, collaborate, and coordinate via education, incentivization, and procurement, to maximize the totality of benefits

Capturing the holistic value of biosimilars in Europe–part 1:a historical perspective

Introduction: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics. Methods: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets. Key insights were also sought from an expert panel of European stakeholders. Results: Survey respondents were clinicians, pharmacists, and payers from Europe (N = 103). Perceived benefits of biosimilars included increased access to innovative medicines (73% of respondents) or biologic treatments (66%). Biosimilar competition was thought to expand access to biologics (~50% of respondents) or drug combinations (~36%) and reduce biologic access time (34%). Key drivers of biologic access after biosimilar competition included increased biologic awareness (51%) and changes to prescribing guidelines (37%) and/or treatment paradigms (28%). The expert panel developed a market maturity framework of biosimilar adoption/opportunities comprising three stages: ‘Invest,’ ‘Expand,’ and ‘Harvest.’ Findings were supported by published literature. Conclusions: In Europe, the perceptions of well-informed survey/interview respondents are that biosimilars have improved patient outcomes via increased access to biologics and innovative biologic products, contributing to earlier and longer treatment of a broader population.</p

The green box: An electronically versatile perylene diimide macrocyclic host for fullerenes

The powerful electron accepting ability of fullerenes makes them ubiquitous components in biomimetic donor–acceptor systems that model the intermolecular electron transfer processes of Nature’s photosynthetic center. Exploiting perylene diimides (PDIs) as components in cyclic host systems for the noncovalent recognition of fullerenes is unprecedented, in part because archetypal PDIs are also electron deficient, making dyad assembly formation electronically unfavorable. To address this, we report the strategic design and synthesis of a novel large, macrocyclic receptor composed of two covalently strapped electron-rich bis-pyrrolidine PDI panels, nicknamed the “Green Box” due to its color. Through the principle of electronic complementarity, the Green Box exhibits strong recognition of pristine fullerenes (C60/70), with the noncovalent ground and excited state interactions that occur upon fullerene guest encapsulation characterized by a range of techniques including electronic absorption, fluorescence emission, NMR and time-resolved EPR spectroscopies, cyclic voltammetry, mass spectrometry, and DFT calculations. While relatively low polarity solvents result in partial charge transfer in the host donor–guest acceptor complex, increasing the polarity of the solvent medium facilitates rare, thermally allowed full electron transfer from the Green Box to fullerene in the ground state. The ensuing charge separated radical ion paired complex is spectroscopically characterized, with thermodynamic reversibility and kinetic stability also demonstrated. Importantly, the Green Box represents a seminal type of C60/70 host where electron-rich PDI motifs are utilized as recognition motifs for fullerenes, facilitating novel intermolecular, solvent tunable ground state electronic communication with these guests. The ability to switch between extremes of the charge transfer energy continuum is without precedent in synthetic fullerene-based dyads

RET Mutational Spectrum in Hirschsprung Disease: Evaluation of 601 Chinese Patients

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial)