Ecosystem services provided by Olympia oyster (Ostrea lurida) habitat and Pacific oyster (Crassostrea gigas) habitat; Dungeness crab (Metacarcinus magister) production in Willapa Bay, WA

Oyster reefs provide an array of ecosystem services. Specifically, they provide structurally complex habitat for fish and invertebrate species such as the commercially important Dungeness crab, Metacarcinus magister. This ecosystem service, once provided by the native oyster Ostrea lurida, is now provided by the commercially cultured oyster Crassostrea gigas in many estuaries on the U.S west coast. An economic investigation was conducted examining the ecosystem services provided by oyster habitat, common economic valuation theories and techniques, and tradeoffs between oyster restoration and aquaculture expansion. A scientific investigation, comprised of three studies, was also conducted to examine Dungeness crab production as an ecosystem service provided by oyster habitat. Because natural ecosystems, such as oyster reefs, provide beneficial goods and services through time, they should be valued as any other economic asset or capital. Until recently many of these beneficial services have not been accounted for within resource management plans, often resulting in the over-exploitation of those resources. Activities such as coastal development, dredging, aquaculture expansion, or even habitat restoration can affect estuarine ecosystems. While valuing the ecosystems themselves might be difficult, valuation of the services they provide can be a useful tool for identifying and protecting key ecosystem services while implementing plans with minimal negative impact. The oysters, O. lurida and C. gigas inhabit different regions of the tidal zone. O. lurida is predominantly found in subtidal and low intertidal regions whereas C. gigas is predominantly found in intertidal regions. The shift in the dominant species has resulted in a subsequent shift of available recruitment habitat for M. magister. We conducted an across-estuary study to examine settlement of M. magister in existing O. lurida, C. gigas, eelgrass, and open mud habitats in Willapa Bay, WA, Netarts Bay, OR, and Coos Bay, OR, to determine tradeoffs in crab production between habitat types. A second study using shell bags as settlement substrate at various tidal elevations was conducted in Yaquina Bay, OR, to obtain density data of M. magister by depth. We used these densities, in combination with pre-existing data from Willapa Bay, to compare the production of Dungeness crab as an ecosystem service historically provided by O. lurida habitat and production currently provided by C. gigas habitat in Willapa Bay, WA. A third study using shell piles was conducted in Yaquina Bay, OR to estimate survival of juvenile M. magister. The results of these three studies generally support prior research indicating that densities of juvenile M. magister are greater in oyster and eelgrass habitats than in open mud, and are generally greater in oyster habitat than in eelgrass. The Yaquina Bay shell bag study indicated greater densities of juvenile M. magister in subtidal regions, while the shell pile study indicated greater densities in higher intertidal regions

Anthelmintic activities against Haemonchus contortus or Trichostrongylus colubriformis from small ruminants are influenced by structural features of condensed tannins

Plants containing condensed tannins (CTs) may hold promise as alternatives to synthetic anthelmintic (AH) drugs for controlling gastrointestinal nematodes (GINs). However, the structural features that contribute to the AH activities of CTs remain elusive. This study probed the relationships between CT structures and their AH activities. Eighteen plant resources were selected based on their diverse CT structures. From each plant resource, two CT fractions were isolated and their in vitro AH activities were measured with the Larval Exsheathment Inhibition Assay, which was applied to Haemonchus contortus and Trichostrongylus colubriformis. Calculation of mean EC50 values indicated that H. contortus was more susceptible than T colubriformis to the different fractions and that the F1 fractions were less efficient than the F2 ones, as indicated by the respective mean values for H.contortus F1 = 136.9 ± 74.1 µg/ml; and for H.contortus F2 = 108.1 ± 53.2 µg/ml and for T colubriformis F1 = 233 ± 54.3 µg/ml and F2=166 ± 39.9 µg/ml. The results showed that the AH activity against H. contortus was associated with the monomeric subunits that give rise to prodelphinidins (P < 0.05) and with CT polymer size (P < 0.10). However, for T. colubriformis AH activity was correlated only with prodelphinidins (P < 0.05). These results suggest that CTs have different modes of action against different parasite species

A platform in the use of medicines to treat chronic hepatitis C (PLATINUM C): Protocol for a prospective treatment registry of real-world outcomes for hepatitis C

© 2020, The Author(s). Background: Safe, highly curative, short course, direct acting antiviral (DAA) therapies are now available to treat chronic hepatitis C. DAA therapy is freely available to all adults chronically infected with the hepatitis C virus (HCV) in Australia. If left untreated, hepatitis C may lead to progressive hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Australia is committed to eliminating hepatitis as a public health threat by 2030 set by the World Health Organization. However, since the introduction of funded DAA treatment, uptake has been suboptimal. Australia needs improved strategies for testing, treatment uptake and treatment completion to address the persisting hepatitis C public health problem. PLATINUM C is a HCV treatment registry and research platform for assessing the comparative effectiveness of alternative interventions for achieving virological cure. Methods: PLATINUM C will prospectively enrol people with active HCV infection confirmed by recent detection of HCV ribonucleic acid (RNA) in blood. Those enrolled will agree to allow standardised collection of demographic, lifestyle, treatment, virological outcome and other relevant clinical data to better inform the future management of HCV infection. The primary outcome is virological cure evidenced by sustained virological response (SVR), which is defined as a negative HCV PCR result 6 to 18 months after initial prescription of DAA therapy and no less than 12 weeks after the completion of treatment. Study participants will be invited to opt-in to medication adherence monitoring and quality of life assessments using validated self-reported instruments (EQ-5D-5L). Discussion: PLATINUM C is a treatment registry and platform for nesting pragmatic trials. Data collected will inform the design, development and implementation of pragmatic trials. The digital infrastructure, study procedures and governing systems established by the registry will allow PLATINUM C to support a wider research platform in the management of hepatitis C in primary care. Trial registration: The trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12619000023156). Date of registration: 10/01/2019

Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation

In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in the discrete stages of angiogenesis can uniquely contribute to vessel branching outcomes

Evolution of olivine lattice preferred orientation during simple shear in the mantle

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Earth and Planetary Science Letters 272 (2008): 501-512, doi:10.1016/j.epsl.2008.03.063.Understanding the variation of olivine lattice preferred orientation (LPO) as a function of shear strain is important for models that relate seismic anisotropy to the kinematics of deformation. We present results on the evolution of olivine orientation as a function of shear strain in samples from a shear zone in the Josephine Peridotite (southwest Oregon). We find that the LPO in harzburgites re-orients from a pre-existing LPO outside the shear zone to a new LPO with the olivine [100] maximum aligned sub-parallel to the shear direction between 168% and 258% shear strain. The strain at which [100] aligns with the shear plane is slightly higher than that observed in experimental samples, which do not have an initial LPO. While our observations broadly agree with the experimental observations, our results suggest that a pre-existing LPO influences the strain necessary for LPO alignment with the shear direction. In addition, olivine re-alignment appears to be dominated by slip on both (010)[100] and (001)[100], due to the orientation of the pre-existing LPO. Fabric strengths, quantified using both the J- and M- indices, do not increase with increasing shear strain. Unlike experimental observations, our natural samples do not have a secondary LPO peak. The lack of a secondary peak suggests that subgrain rotation recrystallization dominates over grain boundary migration during fabric re-alignment. Harzburgites exhibit girdle patterns among [010] and [001] axes, while a dunite has point maxima. Combined with the observation that harzburgites are finer grained than dunites, we speculate that additional phases (i.e., pyroxenes) limit olivine grain growth and promote grain boundary sliding. Grain boundary sliding may relax the requirement for slip on the hardest olivine system, enhancing activation of the two easiest olivine slip systems, resulting in the [010] and [001] girdle patterns. Overall, our results provide an improved framework for calibration of LPO evolution models.This work was partly supported by NSF grants EAR-0230267 and EAR-0409609. Funding for fieldwork was provided by the WHOI Academic Programs Office as part of a 2003 field class run by P.B.K. and G.H

Comparison of LED and Conventional Fluorescence Microscopy for Detection of Acid Fast Bacilli in a Low-Incidence Setting

INTRODUCTION: Light emitting diode fluorescence microscopes have many practical advantages over conventional mercury vapour fluorescence microscopes, which would make them the preferred choice for laboratories in both low- and high-resource settings, provided performance is equivalent. METHODS: In a nested case-control study, we compared diagnostic accuracy and time required to read slides with the Zeiss PrimoStar iLED, LW Scientific Lumin, and a conventional fluorescence microscope (Leica DMLS). Mycobacterial culture was used as the reference standard, and subgroup analysis by specimen source and organism isolated were performed. RESULTS: There was no difference in sensitivity or specificity between the three microscopes, and agreement was high for all comparisons and subgroups. The Lumin and the conventional fluorescence microscope were equivalent with respect to time required to read smears, but the Zeiss iLED was significantly time saving compared to both. CONCLUSIONS: Light emitting diode microscopy should be considered by all tuberculosis diagnostic laboratories, including those in high income countries, as a replacement for conventional fluorescence microscopes. Our findings provide support to the recent World Health Organization policy recommending that conventional fluorescence microscopy be replaced by light emitting diode microscopy using auramine staining in all settings where fluorescence microscopy is currently used

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial

BackgroundRelapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined. MethodsThe REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms. Discussion:Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery. Trial registration: ClinicalTrials.gov: NCT05848765; 08-May-2023. EudraCT: 2022-000677-75; 10-Feb-2022

Benefits of condensed tannins in forage legumes fed to ruminants:Importance of structure, concentration, and diet composition

Condensed tannins (CTs) account for up to 20% of the dry matter in forage legumes used as ruminant feeds. Beneficial animal responses to CTs have included improved growth, milk and wool production, fertility, and reduced methane emissions and ammonia volatilization from dung or urine. Most important is the ability of such forages to combat the effects of gastrointestinal parasitic nematodes. Inconsistent animal responses to CTs were initially attributed to concentration in the diet, but recent research has highlighted the importance of their molecular structures, as well as concentration, and also the composition of the diet containing the CTs. The importance of CT structural traits cannot be underestimated. Interdisciplinary research is the key to unraveling the relationships between CT traits and bioactivities and will enable future on-farm exploitation of these natural plant compounds. Research is also needed to provide plant breeders with guidelines and screening tools to optimize CT traits, in both the forage and the whole diet. In addition, improvements are needed in the competitiveness and agronomic traits of CT-containing legumes and our understanding of options for their inclusion in ruminant diets. Farmers need varieties that are competitive in mixed swards and have predictable bioactivities. This review covers recent results from multidisciplinary research on sainfoin (Onobrychis Mill. spp.) and provides an overview of current developments with several other tanniniferous forages. Tannin chemistry is now being linked with agronomy, plant breeding, animal nutrition, and parasitology. The past decade has yielded considerable progress but also generated more questions — an enviable consequence of new knowledge