Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration

PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payers’ perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (€14,215), followed by aflibercept (€18,202) and ranibizumab (€31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively €507 and €60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (€20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not

Loss of Potential Aquatic-Terrestrial Subsidies Along the Missouri River Floodplain

The floodplains of large rivers have been heavily modified due to riparian development and channel modifications, both of which can eliminate shallow off-channel habitats. The importance of these habitats for aquatic organisms like fishes is well studied. However, loss of off-channel habitat also eliminates habitats for the production of emerging aquatic insects, which subsidize riparian consumers in terrestrial food webs. We used field collections of insect emergence, historical mapping, and statistical modeling to estimate the loss of insect emergence due to channel modifications along eight segments of the Missouri River (USA), encompassing 1566 river km, between 1890 and 2012. We estimate annual production of emerging aquatic insects declined by a median of 36,000 kgC (95% CrI: 3000 to 450,000) between 1890 and 2012 (a 34% loss), due to the loss of surface area in backwaters and related off-channel habitats. Under a conservative assumption that riparian birds obtain 24% of their annual energy budget from adult aquatic insects, this amount of insect loss would be enough to subsidize approximately 790,000 riparan woodland birds during the breeding and nesting period (May to August; 95% CrI: 57,000 to 10,000,000). Most of the loss is concentrated in the lower reaches of the Missouri River, which historically had a wide floodplain, a meandering channel, and a high density of off-channel habitats, but which were substantially reduced due to channelization and bank stabilization. Our results indicate that the loss of off-channel habitats in large river floodplains has the potential to substantially affect energy availability for riparian insectivores, further demonstrating the importance of maintaining and restoring these habitats for linked aquatic-terrestrial ecosystems

The rate of hypo-osmotic challenge influences regulatory volume decrease (RVD) and mechanical properties of articular chondrocytes

Zhao Wang is funded on a China Scholarships PhD Studentship. Jerome Irianto was supported on a project grant from The Wellcome Trust (ref no. 084717)

Fish Species of Greatest Conservation Need in Wadeable Iowa Streams: Current Status and Effectiveness of Aquatic Gap Program Distribution Models

Effective conservation of fish species of greatest conservation need (SGCN) requires an understanding of species– habitat relationships and distributional trends. Thus, modeling the distribution of fish species across large spatial scales may be a valuable tool for conservation planning. Our goals were to evaluate the status of 10 fish SGCN in wadeable Iowa streams and to test the effectiveness of IowaAquatic Gap Analysis Project (IAGAP) species distribution models. We sampled fish assemblages from 86 wadeable stream segments in the Mississippi River drainage of Iowa during 2009 and 2010 to provide contemporary, independent fish species presence–absence data. The frequencies of occurrence in stream segments where species were historically documented varied from 0.0% for redfin shiner Lythrurus umbratilis to 100.0% for American brook lamprey Lampetra appendix, with a mean of 53.0%, suggesting that the status of Iowa fish SGCN is highly variable. Cohen’s kappa values and other model performance measures were calculated by comparing field-collected presence–absence data with IAGAP model–predicted presences and absences for 12 fish SGCN. Kappa values varied from 0.00 to 0.50, with a mean of 0.15. The models only predicted the occurrences of banded darter Etheostoma zonale, southern redbelly dace Phoxinus erythrogaster, and longnose dace Rhinichthys cataractae more accurately than would be expected by chance. Overall, the accuracy of the twelve models was low, with a mean correct classification rate of 58.3%. Poor model performance probably reflects the difficulties associated with modeling the distribution of rare species and the inability of the large-scale habitat variables used in IAGAP models to explain the variation in fish species occurrences. Our results highlight the importance of quantifying the confidence in species distribution model predictions with an independent data set and the need for long-term monitoring to better understand the distributional trends and habitat associations of fish SGCN

Multidimensional Atomic Force Microscopy: A Versatile Novel Technology for Nanopharmacology Research

Nanotechnology is giving us a glimpse into a nascent field of nanopharmacology that deals with pharmacological phenomena at molecular scale. This review presents our perspective on the use of scanning probe microscopy techniques with special emphasis to multidimensional atomic force microscopy (m-AFM) to explore this new field with a particular emphasis to define targets, design therapeutics, and track outcomes of molecular-scale pharmacological interactions. The approach will be to first discuss operating principles of m-AFM and provide representative examples of studies to understand human health and disease at the molecular level and then to address different strategies in defining target macromolecules, screening potential drug candidates, developing and characterizing of drug delivery systems, and monitoring target–drug interactions. Finally, we will discuss some future directions including AFM tip-based parallel sensors integrated with other high-throughput technologies which could be a powerful platform for drug discovery

Assessing the Dutch energy transition policy: how does it deal with dilemmas of managing transitions?

ABSTRACT In the Netherlands, the national government is committed towards altering the systems of energy, transport and agriculture in the name of sustainable development. A process of deliberation and change was started\xe2\x80\x94aimed at achieving \xe2\x80\x98transitions\xe2\x80\x99\xe2\x80\x94using a model of transition management. This paper examines how the new arrangements of governance for energy transition deal with six problems of steering: ambivalence about goals, uncertainty about cause\xe2\x80\x93effect relations, distributed power of control, political myopia, determination of short-term steps for long-term change and the danger of lock-in to new systems. The Dutch experience shows that transition management is applied in ways different from the original model (established players play a too great role) but it appears a useful model of reflexive governance, combining advantages of incremental politics with those of planning. It helps to orientate innovation policy and sectoral policies to sustainable development goals and to exploit business interests in system innovations in a prudent manner

Habitat Associations of Fish Species of Greatest Conservation Need at Multiple Spatial Scales in Wadeable Iowa Streams

Fish and habitat data were collected from 84 wadeable stream reaches in the Mississippi River drainage of Iowa to predict the occurrences of seven fish species of greatest conservation need and to identify the relative importance of habitat variables measured at small (e.g., depth, velocity, and substrate) and large (e.g., stream order, elevation, and gradient) scales in terms of their influence on species occurrences. Multiple logistic regression analysis was used to predict fish species occurrences, starting with all possible combinations of variables (5 large-scale variables, 13 small-scale variables, and all 18 variables) but limiting the final models to a maximum of five variables. Akaike’s information criterion was used to rank candidate models, weight model parameters, and calculate model-averaged predictions. On average, the correct classification rate (CCR = 80%) and Cohen’s kappa (κ = 0.59) were greatest for multiple-scale models (i.e., those including both large-scale and small-scale variables), intermediate for small-scale models (CCR = 75%; κ = 0.49), and lowest for large-scale models (CCR = 73%; κ = 0.44). The occurrence of each species was associated with a unique combination of large-scale and small-scale variables. Our results support the necessity of understanding factors that constrain the distribution of fishes across spatial scales to ensure that management decisions and actions occur at the appropriate scale

GMOs: Non-Health Issues

The controversy over genetically modified [GM] organisms is often framed in terms of possible hazards for human health. Articles in a previous volume of this *Encyclopedia* give a general overview of GM crops [@Mulvaney2014] and specifically examine human health [@Nordgard2014] and labeling [@Bruton2014] issues surrounding GM organisms. This article explores several other aspects of the controversy: environmental concerns, political and legal disputes, and the aim of "feeding the world" and promoting food security. Rather than discussing abstract, hypothetical GM organisms, this article explores the consequences of the GM organisms that have actually been deployed in the particular contexts that they have been deployed, on the belief that there is little point in discussing GM organisms in an idealized or context-independent way

Effects of Commercial Harvest on Shovelnose Sturgeon Populations in the Upper Mississippi River

Shovelnose sturgeon Scaphirhynchus platorynchus have become an increasingly important commercial species in the upper Mississippi River (UMR) because of the collapse of foreign sturgeon (family Acipenseridae) populations and bans on imported caviar. In response to concerns about the sustainability of the commercial shovelnose sturgeon fishery in the UMR, we undertook this study to describe the demographics of the shovelnose sturgeon population and evaluate the influence of commercial harvest on shovelnose sturgeon populations in the UMR. A total of 1,682 shovelnose sturgeon were collected from eight study pools in 2006 and 2007 (Pools 4, 7, 9, 11, 13, 14, 16, and 18). Shovelnose sturgeon from upstream pools generally had greater lengths, weights, and ages than those from downstream pools. Additionally, mortality estimates were lower in upstream pools (Pools 4, 7, 9, and 11) than in downstream pools (Pools 13, 14, 16, and 18). Linear regression suggested that the slower growth of shovelnose sturgeon is a consequence of commercial harvest in the UMR. Modeling of potential management scenarios suggested that a 685-mm minimum length limit is necessary to prevent growth and recruitment overfishing of shovelnose sturgeon in the UMR