Future trends of marine fish biomass distributions from the North Sea to the Barents Sea.

Climate warming is one of the facets of anthropogenic global change predicted to increase in the future, its magnitude depending on present-day decisions. The north Atlantic and Arctic Oceans are already undergoing community changes, with warmer-water species expanding northwards, and colder-water species retracting. However, the future extent and implications of these shifts remain unclear. Here, we fitted a joint species distribution model to occurrence data of 107, and biomass data of 61 marine fish species from 16,345 fishery independent trawls sampled between 2004 and 2022 in the northeast Atlantic Ocean, including the Barents Sea. We project overall increases in richness and declines in relative dominance in the community, and generalised increases in species' ranges and biomass across three different future scenarios in 2050 and 2100. The projected decline of capelin and the practical extirpation of polar cod from the system, the two most abundant species in the Barents Sea, drove an overall reduction in fish biomass at Arctic latitudes that is not replaced by expanding species. Furthermore, our projections suggest that Arctic demersal fish will be at high risk of extinction by the end of the century if no climate refugia is available at eastern latitudes.

Role of PLGA Variability in Controlled Drug Release from Dexamethasone Intravitreal Implants.

Long-acting injectable formulations based on poly(lactide-co-glycolide) (PLGA) have been commercialized for over 30 years in at least 20 FDA-approved products. These formulations offer several advantages, including reduced dosing frequency, improved patient compliance, and maintenance of therapeutic levels of drug. Despite extensive studies, the inherent complexity of the PLGA copolymer still poses significant challenges associated with the development of generic formulations having drug release profiles equivalent to those of the reference listed drugs. In addition, small changes to PLGA physicochemical properties or the drug product manufacturing process can have a major impact on the drug release profile of these long-acting formulations. This work seeks to better understand how variability in the physicochemical properties of similar PLGAs affects drug release from PLGA solid implants using Ozurdex (dexamethasone intravitreal implant) as the model system. Four 50:50, acid-terminated PLGAs of similar molecular weights were used to prepare four dexamethasone intravitreal implants structurally equivalent to Ozurdex. The PLGAs were extensively characterized by using a variety of analytical techniques prior to implant manufacture using a continuous, hot-melt extrusion process. In vitro release testing of the four structurally equivalent implants was performed in both normal saline and phosphate-buffered saline (PBS), yielding drastically different results between the two methods. In normal saline, no differences in the release profiles were observed. In PBS, the drug release profiles were sensitive to small changes in the residual monomer content, carboxylic acid end group content, and blockiness of the polymers. This finding further underscores the need for a physiologically relevant in vitro release testing method as part of a robust quality control strategy for PLGA-based solid implant formulations.

A Chewing Study of Abuse-Deterrent Tablets Containing Polyethylene Oxide Using a Robotic Simulator.

Abuse-deterrent formulations (ADFs) refer to formulation technologies aiming to deter the abuse of prescription drugs by making the dosage forms difficult to manipulate or extract the opioids. Assessments are required to evaluate the performance of the drugs through different routes including injection, ingestion, and insufflation and also when the drugs are manipulated. Chewing is the easiest and most convenient way to manipulate the drugs and deserves investigation. Chewing is one of the most complex bioprocesses, where the ingested materials are subject to periodic tooth crushing, mixed through the tongue, and lubricated and softened by the saliva. Inter- and intra-subject variations in chewing patterns may result in different chewing performances. The purpose of this study is to use a chewing simulator to assess the deterrent properties of tablets made of polyethylene oxide (PEO). The simulator can mimic human molar grinding with variable chewing parameters including molar trajectory, chewing frequency, and saliva flow rate. To investigate the effects of these parameters, the sizes of the chewed tablet particles and the chewing force were measured to evaluate the chewing performance. Thirty-four out of forty tablets were broken into pieces. The results suggested that the simulator can chew the tablets into smaller particles and that the molar trajectory and saliva flow rate had significant effect on reducing the size of the particles by analysis of variance (ANOVA) while the effect of chewing frequency was not clear. Additionally, chewing force can work as an indicator of the chewing performance.

Numbers of fish species, higher taxa, and phylogenetic similarity decrease with latitude and depth, and deep-sea assemblages are unique.

Species richness has been found to increase from the poles to the tropics but with a small dip near the equator over all marine fishes. Phylogenetic diversity measures offer an alternative perspective on biodiversity linked to evolutionary history. If phylogenetic diversity is standardized for species richness, then it may indicate places with relatively high genetic diversity. Latitudes and depths with both high species and phylogenetic diversity would be a priority for conservation. We compared latitudinal and depth gradients of species richness, and three measures of phylogenetic diversity, namely average phylogenetic diversity (AvPD), the sum of the higher taxonomic levels (STL) and the sum of the higher taxonomic levels divided by the number of species (STL/spp) for modelled ranges of 5,619 marine fish species. We distinguished all, bony and cartilaginous fish groups and four depth zones namely: whole water column; 0 -200 m; 201-1,000 m; and 1,001-6,000 m; at 5°  latitudinal intervals from 75°S to 75°N, and at 100 m depth intervals from 0 m to 3,500 m. Species richness and higher taxonomic richness (STL) were higher in the tropics and subtropics with a small dip at the equator, and were significantly correlated among fish groups and depth zones. Species assemblages had closer phylogenetic relationships (lower AvPD and STL/spp) in warmer (low latitudes and shallow water) than colder environments (high latitudes and deep sea). This supports the hypothesis that warmer shallow latitudes and depths have had higher rates of evolution across a range of higher taxa. We also found distinct assemblages of species in different depth zones such that deeper sea species are not simply a subset of shallow assemblages. Thus, conservation needs to be representative of all latitudes and depth zones to encompass global biodiversity.

Widespread support for a global species list with a formal governance system.

Taxonomic data are a scientific common. Unlike nomenclature, which has strong governance institutions, there are currently no generally accepted governance institutions for the compilation of taxonomic data into an accepted global list. This gap results in challenges for conservation, ecological research, policymaking, international trade, and other areas of scientific and societal importance. Consensus on a global list and its management requires effective governance and standards, including agreed mechanisms for choosing among competing taxonomies and partial lists. However, governance frameworks are currently lacking, and a call for governance in 2017 generated critical responses. Any governance system to which compliance is voluntary requires a high level of legitimacy and credibility among those by and for whom it is created. Legitimacy and credibility, in turn, require adequate and credible consultation. Here, we report on the results of a global survey of taxonomists, scientists from other disciplines, and users of taxonomy designed to assess views and test ideas for a new system of taxonomic list governance. We found a surprisingly high degree of agreement on the need for a global list of accepted species and their names, and consistent views on what such a list should provide to users and how it should be governed. The survey suggests that consensus on a mechanism to create, manage, and govern a single widely accepted list of all the world's species is achievable. This finding was unexpected given past controversies about the merits of list governance.

Manufacturing dexamethasone intravitreal implants: Process control and critical quality attributes.

Over 20 long-acting injectable formulations based on poly(lactide-co-glycolide) (PLGA) have been approved by the FDA to date. PLGA is a biodegradable polymer that can extend drug release from these dosage forms for up to six months after administration. Despite the commercial success of several of these formulations, there are still a limited number of products that utilize PLGA, and there are currently no generic counterparts of these products on the market. Significant technical challenges are associated with preparation of chemically and structurally equivalent formulations that yield an equivalent drug release profile to the reference listed drug (RLD) both in vitro and in vivo. In this work, Ozurdex (dexamethasone intravitreal implant) was used as a model system to explore how the manufacturing process of PLGA-based solid implants impacts the quality and performance of the dosage form. Control of implant structural characteristics, including diameter, internal porosity, and surface roughness, was required to maintain accurate unit dose potency. Implants were prepared by a continuous hot-melt extrusion process that was thoroughly characterized to show the importance of precise feeding control to meet dimensional specifications. Five extruder die designs were evaluated using the same hot-melt extrusion process to produce five structurally-distinct implants. The structural differences did not alter the in vitro drug release profile when tested in both normal saline and phosphate-buffered saline (pH 7.4); however, implant porosity was shown to impact the mechanical strength of the implants. This work seeks to provide insight into the manufacturing process of PLGA-based solid implants to support development of future novel and generic drug products.

Over 20% of marine fishes shifting in the North and Barents Seas, but not in the Norwegian Sea.

Climate warming generally induces poleward range expansions and equatorward range contractions of species' environmental niches on a global scale. Here, we examined the direction and magnitude of species biomass centroid geographic shifts in relation to temperature and depth for 83 fish species in 9,522 standardised research trawls from the North Sea (1998-2020) to the Norwegian (2000-2020) and Barents Sea (2004-2020). We detected an overall significant northward shift of the marine fish community biomass in the North Sea, and individual species northward shifts in the Barents and North Seas, in 20% and 25% of the species' biomass centroids in each respective region. We did not detect overall community shifts in the Norwegian Sea, where two species (8%) shifted in each direction (northwards and southwards). Among 9 biological traits, species biogeographic assignation, preferred temperature, age at maturity and maximum depth were significant explanatory variables for species latitudinal shifts in some of the study areas, and Arctic species shifted significantly faster than boreal species in the Barents Sea. Overall, our results suggest a strong influence of other factors, such as biological interactions, in determining several species' recent geographic shifts.

Body size and trophic level increase with latitude, and decrease in the deep-sea and Antarctica, for marine fish species.

The functional traits of species depend both on species' evolutionary characteristics and their local environmental conditions and opportunities. The temperature-size rule (TSR), gill-oxygen limitation theory (GOLT), and temperature constraint hypothesis (TCH) have been proposed to explain the gradients of body size and trophic level of marine species. However, how functional traits vary both with latitude and depth have not been quantified at a global scale for any marine taxon. We compared the latitudinal gradients of trophic level and maximum body size of 5,619 marine fish from modelled species ranges, based on (1) three body size ranges, <30, 30-100, and >100 cm, and (2) four trophic levels, <2.20, 2.20-2.80, 2.81-3.70, >3.70. These were parsed into 5° latitudinal intervals in four depth zones: whole water column, 0-200, 201-1,000, and 1,001-6,000 m. We described the relationship between latitudinal gradients of functional traits and salinity, sea surface and near seabed temperatures, and dissolved oxygen. We found mean body sizes and mean trophic levels of marine fish were smaller and lower in the warmer latitudes, and larger and higher respectively in the high latitudes except for the Southern Ocean (Antarctica). Fish species with trophic levels ≤2.80 were dominant in warmer and absent in colder environments. We attribute these differences in body size and trophic level between polar regions to the greater environmental heterogeneity of the Arctic compared to Antarctica. We suggest that fish species' mean maximum body size declined with depth because of decreased dissolved oxygen. These results support the TSR, GOLT and TCH hypotheses respectively. Thus, at the global scale, temperature and oxygen are primary factors affecting marine fishes' biogeography and biological traits.

Progress in the discovery of isopods (Crustacea: Peracarida)-is the description rate slowing down?

Taxonomic species are the best standardised metric of biodiversity. Therefore, there is broad scientific and public interest in how many species have already been named and how many more may exist. Crustaceans comprise about 6% of all named animal species and isopods about 15% of all crustaceans. Here, we review progress in the naming of isopods in relation to the number of people describing new species and estimate how many more species may yet be named by 2050 and 2100, respectively. In over two and a half centuries of discovery, 10,687 isopod species in 1,557 genera and 141 families have been described by 755 first authors. The number of authors has increased over time, especially since the 1950s, indicating increasing effort in the description of new species. Despite that the average number of species described per first author has declined since the 1910s, and the description rate has slowed down over the recent decades. Authors' publication lifetimes did not change considerably over time, and there was a distinct shift towards multi-authored publications in recent decades. Estimates from a non-homogeneous renewal process model predict that an additional 660 isopod species will be described by 2100, assuming that the rate of description continues at its current pace.

Fishery catch is affected by geographic expansion, fishing down food webs and climate change in Aotearoa, New Zealand.

Historical fishing effort has resulted, in many parts of the ocean, in increasing catches of smaller, lower trophic level species once larger higher trophic level species have been depleted. Concurrently, changes in the geographic distribution of marine species have been observed as species track their thermal affinity in line with ocean warming. However, geographic shifts in fisheries, including to deeper waters, may conceal the phenomenon of fishing down the food web and effects of climate warming on fish stocks. Fisheries-catch weighted metrics such as the Mean Trophic Level (MTL) and Mean Temperature of the Catch (MTC) are used to investigate these phenomena, although apparent trends of these metrics can be masked by the aforementioned geographic expansion and deepening of fisheries catch across large areas and time periods. We investigated instances of both fishing down trophic levels and climate-driven changes in the geographic distribution of fished species in New Zealand waters from 1950-2019, using the MTL and MTC. Thereafter, we corrected for the masking effect of the geographic expansion of fisheries within these indices by using the Fishing-in-Balance (FiB) index and the adapted Mean Trophic Level (aMTL) index. Our results document the offshore expansion of fisheries across the New Zealand Exclusive Economic Zone (EEZ) from 1950-2019, as well as the pervasiveness of fishing down within nearshore fishing stock assemblages. We also revealed the warming of the MTC for pelagic-associated fisheries, trends that were otherwise masked by the depth- and geographic expansion of New Zealand fisheries across the study period.

Hurdles and opportunities in implementing marine biosecurity systems in data-poor regions.

Managing marine nonindigenous species (mNIS) is challenging, because marine environments are highly connected, allowing the dispersal of species across large spatial scales, including geopolitical borders. Cross-border inconsistencies in biosecurity management can promote the spread of mNIS across geopolitical borders, and incursions often go unnoticed or unreported. Collaborative surveillance programs can enhance the early detection of mNIS, when response may still be possible, and can foster capacity building around a common threat. Regional or international databases curated for mNIS can inform local monitoring programs and can foster real-time information exchange on mNIS of concern. When combined, local species reference libraries, publicly available mNIS databases, and predictive modeling can facilitate the development of biosecurity programs in regions lacking baseline data. Biosecurity programs should be practical, feasible, cost-effective, mainly focused on prevention and early detection, and be built on the collaboration and coordination of government, nongovernment organizations, stakeholders, and local citizens for a rapid response.

Drug release mechanisms of high-drug-load, melt-extruded dexamethasone intravitreal implants.

Ozurdex is an FDA-approved sustained-release, biodegradable implant formulated to deliver the corticosteroid dexamethasone to the posterior segment of the eye for up to 6 months. Hot-melt extrusion is used to prepare the 0.46 mm × 6 mm, rod-shaped implant by embedding the drug in a matrix of poly(lactic-co-glycolic acid) (PLGA) in a 60:40 drug:polymer ratio by weight. In our previous work, the Ozurdex implant was carefully studied and reverse engineered to produce a compositionally and structurally equivalent implant for further analysis. In this work, the reverse-engineered implant was thoroughly characterized throughout the in vitro dissolution process to elucidate the mechanisms of controlled drug release. The implant exhibited a triphasic release profile in 37 °C normal saline with a small burst release (1-2 %), a one-week lag phase with limited release (less than 10 %), and a final phase where the remainder of the dose was released over 3-4 weeks. The limited intermolecular interaction between dexamethasone and PLGA rendered the breakdown of the polymer the dominating mechanism of controlled release. A close relationship between drug release and total implant mass loss was observed. Unique chemical and structural differences were seen between the core of the implant and the implant surface driven by diffusional limitations, autocatalytic hydrolysis, and osmotic effects.

Oceanographic connectivity explains the intra-specific diversity of mangrove forests at global scales.

The distribution of mangrove intra-specific biodiversity can be structured by historical demographic processes that enhance or limit effective population sizes. Oceanographic connectivity (OC) may further structure intra-specific biodiversity by preserving or diluting the genetic signatures of historical changes. Despite its relevance for biogeography and evolution, the role of oceanographic connectivity in structuring the distribution of mangrove's genetic diversity has not been addressed at global scale. Here we ask whether connectivity mediated by ocean currents explains the intra-specific diversity of mangroves. A comprehensive dataset of population genetic differentiation was compiled from the literature. Multigenerational connectivity and population centrality indices were estimated with biophysical modeling coupled with network analyses. The variability explained in genetic differentiation was tested with competitive regression models built upon classical isolation-by-distance (IBD) models considering geographic distance. We show that oceanographic connectivity can explain the genetic differentiation of mangrove populations regardless of the species, region, and genetic marker (significant regression models in 95% of cases, with an average R-square of 0.44 ± 0.23 and Person's correlation of 0.65 ± 0.17), systematically improving IBD models. Centrality indices, providing information on important stepping-stone sites between biogeographic regions, were also important in explaining differentiation (R-square improvement of 0.06 ± 0.07, up to 0.42). We further show that ocean currents produce skewed dispersal kernels for mangroves, highlighting the role of rare long-distance dispersal events responsible for historical settlements. Overall, we demonstrate the role of oceanographic connectivity in structuring mangrove intra-specific diversity. Our findings are critical for mangroves' biogeography and evolution, but also for management strategies considering climate change and genetic biodiversity conservation.

Reverse engineering the Ozurdex dexamethasone intravitreal implant.

Ozurdex is a biodegradable implant formulated for sustained-release delivery of the corticosteroid dexamethasone to the posterior segment of the eye. The small, rod-shaped implant is administered directly to the vitreous using a dedicated applicator, and releases drug for up to 6 months after administration. Sustained release is achieved by embedding dexamethasone in a matrix of 50:50 poly(lactic-co-glycolic acid) (PLGA). In this work, the Ozurdex implant was thoroughly characterized to enable the reverse engineering of a compositionally and structurally equivalent implant. Advanced imaging techniques such as scanning electron microscopy (SEM) and microcomputed tomography (microCT) revealed that the Ozurdex implant exhibits an irregular surface and an internal porosity of 6% due to a large number of discrete voids approximately 3 µm in diameter. Thermal and spectroscopic analyses showed limited interaction between the drug and the polymer, resulting in a two-phase system of dexamethasone crystals embedded within a PLGA matrix. Reverse-engineered implants with properties similar to Ozurdex were prepared using a two-step hot-melt extrusion process. The reverse-engineered implants exhibited a triphasic drug release profile similar to Ozurdex. This work seeks to provide insight into the manufacturing process and characterization of PLGA-based solid implants to support future generic product development.

Three decades of increasing fish biodiversity across the northeast Atlantic and the Arctic Ocean.

Observed range shifts of numerous species support predictions of climate change models that species will shift their distribution northward into the Arctic and sub-Arctic seas due to ocean warming. However, how this is affecting overall species richness is unclear. Here we analyze 20,670 scientific research trawls from the North Sea to the Arctic Ocean collected from 1994 to 2020, including 193 fish species. We found that demersal fish species richness at the local scale has doubled in some Arctic regions, including the Barents Sea, and increased at a lower rate at adjacent regions in the last three decades, followed by an increase in species richness and turnover at a regional scale. These changes in biodiversity correlated with an increase in sea bottom temperature. Within the study area, Arctic species' probability of occurrence generally declined over time. However, the increase in species from southern latitudes, together with an increase in some Arctic species, ultimately led to an enrichment of the Arctic and sub-Arctic marine fauna due to increasing water temperature consistent with climate change.

Climate change projections show shrinking deep-water ecosystems with implications for biodiversity and aquaculture in the Northwest Pacific.

The increased availability of environmental data with depth deriving from remote-sensing-based datasets permits more comprehensive modelling of the distribution of marine ecosystems in space and time. This research tests the potential of such objective modelling of marine ecosystems in four dimensions, spatial and temporal, to provide projections of how climate change may affect biodiversity, including aquaculture. This approach could be replicated for any regional seas. The Bohai Sea, Yellow Sea, and East China Sea (BYECS) are marginal seas in the Northwest Pacific bounded by China, Korea, and Japan. Despite providing important ecological and economic services, their ecological conditions and ecosystems distribution have not yet been systematically mapped. This analysis used 13 marine environmental variables, measured on a three-dimensional and monthly basis during 1993-2019, to classify and map the BYECS region by k-means clustering using cosine similarity as distance function. There were 13 distinct areas identified that fit the definition of "ecosystems" that is, enduring regions demarcated by environmental characteristics. Of these 13 ecosystems, the Yellow Sea Cold Water (YSCW) Ecosystem is significant in relation to seasonal species composition and the newly developing deep-sea salmon caging aquaculture in the region. Projections of the potential size of this water mass under various climate-change scenarios based on analysis using the Non-Parametric Probabilistic Ecological Niche (NPPEN) model show that its volume may decrease 31 %-66 % in the future. Such a decrease would have impacts on the seasonal species' abundances in the BYECS marginal sea region and threaten the deep-sea cold-water salmon farming.

Twin-Screw Continuous Mixing Can Produce Dry Powder Inhalation Mixtures for Pulmonary Delivery.

The feasibility of twin-screw corotating extruder as a continuous process mixer to prepare dry powder inhalation (DPI) powders was investigated. Interactive mixtures of 1% micronized budesonide, 0.3% magnesium stearate and 98.7% alpha-lactose monohydrate were manufactured using a Leistritz Nano-16 extruder at various processing conditions. One set of GFM (grooved mixing) elements were included in the screw profile to provide distributive mixing of conveyed powders with the goal of resulting in a homogeneous mixture. Residence time in the twin-screw mixer was modelled to quantify mixing efficiency. Comparative powders were also prepared using either low or high-shear batch mixing to compare the effect of mixing methods on the properties of the budesonide dry powder inhalation formulation. Twin screw mixing results in homogeneous mixtures with aerosol performance comparable to that of high-shear batch mixing. Scanning electron microscopy confirmed that twin screw mixing produces particles with morphology like that of low and high-shear batch mixing. X-ray diffraction (XRD) analysis verified that there was no form change of the drug due to twin-screw processing. Statistical regression was used to probe the relationship between twin screw mixing process parameters such as screw speed and feed rate and aerosol performance. The twin screw mixing process was found to be robust, as no significant differences in aerosol performance were found for various processing parameters.