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Recent spikes in interactions between humans and sharks in the New York Bight have sparked widespread reporting of possible causalities, many of which lack empirical support. Here we comment on the current state of knowledge regarding shark biology and management in New York waters emphasizing that the possible drivers of increased human–shark interactions are confounded by a lack of historical monitoring data. We outline several key research avenues that should be considered to ensure the safe and sustainable coexistence of humans, sharks, and their prey, in an era of accelerated environmental change. [ABSTRACT FROM AUTHOR]

Identifying potential links between food web structure and animal body condition is fundamental for predicting the long‐term persistence of populations under rapidly changing environments. Northern lakes, and the cold‐water adapted species that inhabit them, are particularly vulnerable to a warming climate.We explored relationships among body condition and energy channel use in lake trout (Salvelinus namaycush) and seasonal variation in food‐chain length in the Lake of Two Rivers, Ontario, Canada. Bayesian mixing models using carbon isotope values (δ13C) of essential amino acids showed that individuals utilising multiple energy channels had higher gonad mass, suggesting that dietary diversity has reproductive fitness benefits.Amino acid nitrogen isotope (δ15N) analysis revealed seasonal variation in food chain length, with extension of the food web during winter and spring and truncation of the food web during summer. Although these findings illustrate increased omnivory of lake trout during summer, there was no clear evidence that seasonal changes in food chain length had an impact on trout condition.These findings provide new insight into potential relationships between food web structure, energy flow and consumer condition in freshwater ecosystems, thereby revealing potential responses of species to shifting ecosystem states under intensifying climate change at high latitudes. [ABSTRACT FROM AUTHOR]

Robustly quantifying dietary resource use and trophic position using stable isotopes requires accurate trophic discrimination factors (TDF; Δ13C and Δ15N for carbon and nitrogen, respectively), defined as the isotopic difference between consumer and diet. Early TDF studies converged on values of around 1.0‰ for Δ13C and 3.4‰ for Δ15N but more recent work indicates that TDF values may be more nuanced, depending on taxa, tissues, trophic level and diets. Yet, the relative importance of these factors remains unclear.Focusing on vertebrates (birds, fish, herptiles and mammals), we conducted a literature review of 279 studies that estimated TDF values and used a Bayesian framework to determine how tissue type, trophic level and diet source influence variation in Δ13C and Δ15N. Additionally, we reviewed 358 trophic ecology studies to determine if studies accounted for these factors during their TDF selection process.For Δ13C, vertebrates showed consistent patterns among tissue types (likely influenced by amino acid composition) and between trophic levels and diet sources (likely a result of dietary protein content and metabolic routing). Comparatively, for Δ15N, vertebrates showed considerable variation among tissue types and trophic levels, likely due to differences in tissue synthesis and physiological capabilities. Overall, Δ13C ranged from −5.1‰ to 9.1‰ and Δ15N from −3.3‰ to 9.7‰, underscoring that 1.0‰ for Δ13C and 3.4‰ for Δ15N are not universally appropriate. Moreover, both Δ13C and Δ15N varied by more than 9‰ within a single species and tissue type, demonstrating that using TDF values from the same, or similar, species may not be appropriate if diet and trophic level are not considered.Despite the importance of diet source on TDF values, most trophic ecology studies did not account for it. Further, most fish studies relied on literature review values that failed to account for tissue type, trophic level and diet source. To aid ecologists in diet and trophic assessments of vertebrates, we used our meta‐analysis to model taxon‐specific TDF estimates (mean ± SD) for each tissue type, trophic level and diet source combination. These more refined TDF values should improve ecological assessments that use stable isotopes. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Public participation in research, also known as citizen science, is being increasingly adopted for the analysis of biological volumetric data. Researchers working in this domain are applying online citizen science as a scalable distributed data analysis approach, with recent research demonstrating that non-experts can productively contribute to tasks such as the segmentation of organelles in volume electron microscopy data. This, alongside the growing challenge to rapidly process the large amounts of biological volumetric data now routinely produced, means there is increasing interest within the research community to apply online citizen science for the analysis of data in this context. Here, we synthesise core methodological principles and practices for applying citizen science for analysis of biological volumetric data. We collate and share the knowledge and experience of multiple research teams who have applied online citizen science for the analysis of volumetric biological data using the Zooniverse platform (www.zooniverse.org). We hope this provides inspiration and practical guidance regarding how contributor effort via online citizen science may be usefully applied in this domain. [ABSTRACT FROM AUTHOR]

Background: The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. Main text: Trial estimands provide a broader perspective compared to the limitations of ITT and per-protocol analysis. Trial treatment effects depend on how events occurring after treatment initiation such as use of alternative medication or discontinuation of the intervention are included in the definition. These events can be accounted for in different ways, depending on the clinical question of interest. Conclusion: The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines. [ABSTRACT FROM AUTHOR]

Background: Systematic literature searches are the cornerstone of systematic reviews. In this study, we evaluated database coverage of randomized clinical trials for central serous chorioretinopathy (CSC). Methods: We searched 12 databases (BIOSIS Previews, CINAHL, the Cochrane Central, Current Contents Connect, Data Citation Index, Derwent Innovations Index, EMBASE, KCI-Korean Journal Database, MEDLINE, PubMed, SciELO Citation Index, and Web of Science Core Collection) on 10 April 2023 for randomized clinical trials for CSC. After identifying all eligible studies across all databases, we investigated the coverage of these studies within each database, including the coverage of any combination of two databases. Results: The 12 databases yielded 848 records for screening, of which 76 were randomized clinical trials for CSC. No single database provided full coverage. The most comprehensive coverage was provided by EMBASE (88%), the Cochrane Central (87%), and PubMed (75%). A combined search in the Cochrane Central and PubMed led to complete coverage (100%) while reducing the number of records for screening from 848 to 279. Conclusions: Systematic review search design should include multiple databases. For randomized clinical trials for CSC, the combination of the Cochrane Central and PubMed provides an excellent balance between coverage and workload. [ABSTRACT FROM AUTHOR]

Understanding the factors shaping patterns of ecological resilience is critical for mitigating the loss of global biodiversity. Throughout aquatic environments, highly mobile predators are thought to serve as important vectors of energy between ecosystems thereby promoting stability and resilience. However, the role these predators play in connecting food webs and promoting energy flow remains poorly understood in most contexts. Using carbon and nitrogen isotopes, we quantified the use of several prey resource pools (small oceanic forage, large oceanics, coral reef, and seagrass) by 17 species of elasmobranch fishes (n = 351 individuals) in The Bahamas to determine their functional diversity and roles as ecosystem links. We observed remarkable functional diversity across species and identified four major groups responsible for connecting discrete regions of the seascape. Elasmobranchs were responsible for promoting energetic connectivity between neritic, oceanic and deep-sea ecosystems. Our findings illustrate how mobile predators promote ecosystem connectivity, underscoring their functional significance and role in supporting ecological resilience. More broadly, strong predator conservation efforts in developing island nations, such as The Bahamas, are likely to yield ecological benefits that enhance the resilience of marine ecosystems to combat imminent threats such as habitat degradation and climate change. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is an ophthalmological emergency that can be difficult to diagnose and prompt treatment is vital. We investigated the sequential diagnostic value for patients with suspected GCA using three biochemical measures as they arrive to the clinician: first, platelet count, then C-reactive protein (CRP), and lastly, erythrocyte sedimentation rate (ESR). This retrospective cross-sectional study of consecutive patients with suspected GCA investigated platelet count, CRP, and ESR using diagnostic test accuracy statistics and odds ratios (ORs) in a sequential fashion. The diagnosis was established by experts at follow-up, considering clinical findings and tests including temporal artery biopsy. A total of 94 patients were included, of which 37 (40%) were diagnosed with GCA. Compared with those without GCA, patients with GCA had a higher platelet count (p < 0.001), CRP (p < 0.001), and ESR (p < 0.001). Platelet count demonstrated a low sensitivity (38%) and high specificity (88%); CRP, a high sensitivity (86%) and low specificity (56%); routine ESR, a high sensitivity (89%) and low specificity (47%); and age-adjusted ESR, a moderate sensitivity (65%) and moderate specificity (65%). Sequential analysis revealed that ESR did not provide additional value in evaluating risk of GCA. Initial biochemical evaluation can be based on platelet count and CRP, without waiting for ESR, which allows faster initial decision-making in GCA. [ABSTRACT FROM AUTHOR]

With normal retinal blood flow, cross-sectional optical coherence tomography (OCT) of retinal vessels shows a structured intravascular reflectivity profile, resembling a 'figure-of-8'. Altered profiles have been reported in vascular occlusive and haematological diseases. Giant cell arteritis (GCA) can cause visual loss, usually due to anterior ischaemic optic neuropathy (AION) or retinal artery occlusion. Our aim was to extend the assessment of OCT vascular profiles to patients with suspected GCA and to determine if any abnormalities were related to GCA per se or to ischaemic ocular conditions. This nested retrospective study included 61 eyes of 31 patients (13 with GCA). Six eyes had arteritic and seven eyes non-arteritic AION, three eyes had non-arteritic retinal artery occlusion, 11 eyes had other ocular conditions and 34 were unaffected control eyes. For each eye the appearance of structured intravascular profiles on peripapillary OCT was graded as present, partial, absent or uncertain. Non-presence of structured intravascular profiles was more frequent in AION and retinal artery occlusion than in other ocular conditions or unaffected eyes (Fisher's test, p =.0047). Based on follow-up of 25 eyes, reflectivity profiles normalised in three out of four eyes after 85 (35–245) days. Vessel profiles were not associated with GCA (p =.32) and were similar in arteritic and non-arteritic AION (p =.66). In conclusion, absence of structured intravascular reflectivity profiles may be a marker of acute ischaemia in the anterior optic nerve or inner retina. However, it did not seem specific for GCA. The prognostic value warrants further studies. [ABSTRACT FROM AUTHOR]

Understanding how intraspecific variation in the use of prey resources impacts energy metabolism has strong implications for predicting long-term fitness and is critical for predicting population-to-community level responses to environmental change. Here, we examine the energetic consequences of variable prey resource use in a widely distributed marine carnivore, juvenile sand tiger sharks (Carcharias taurus). We used carbon and nitrogen isotope analysis to identify three primary prey resource pools—demersal omnivores, pelagic forage, and benthic detritivores and estimated the proportional assimilation of each resource using Bayesian mixing models. We then quantified how the utilization of these resource pools impacted the concentrations of six plasma lipids and how this varied by ontogeny. Sharks exhibited variable reliance on two of three predominant prey resource pools: demersal omnivores and pelagic forage. Resource use variation was a strong predictor of energetic condition, whereby individuals more reliant upon pelagic forage exhibited higher blood plasma concentrations of very low-density lipoproteins, cholesterol, and triglycerides. These findings underscore how intraspecific variation in resource use may impact the energy metabolism of animals, and more broadly, that natural and anthropogenically driven fluctuations in prey resources could have longer term energetic consequences. [ABSTRACT FROM AUTHOR]

Hypomelanosis refers to a suite of skin pigment abnormalities, including albinism, leucism and piebaldism. While documented across many vertebrate species, examples of hypomelanosis are rarely seen in chondrichthyans, with little insight into the potential effects on survival. Here, we report the first observation of abnormal skin pigmentation indicative of piebaldism in the Atlantic nurse shark Ginglymostoma cirratum, representing only the second reported case of skin aberrations for this species. This extremely rare observation is discussed in the broader context of fitness variation and long‐term survival. [ABSTRACT FROM AUTHOR]

Nitrogen isotope (δ15N) analysis of bulk tissues and individual amino acids (AA) can be used to assess how consumers maintain nitrogen balance with broad implications for predicting individual fitness. For elasmobranchs, a ureotelic taxa thought to be constantly nitrogen limited, the isotopic effects associated with nitrogen-demanding events such as prolonged gestation remain unknown. Given the linkages between nitrogen isotope variation and consumer nitrogen balance, we used AA δ15N analysis of muscle and liver tissue collected from female bonnethead sharks (Sphyrna tiburo, n = 16) and their embryos (n = 14) to explore how nitrogen balance may vary across gestation. Gestational stage was a strong predictor of bulk tissue and AA δ15N values in pregnant shark tissues, decreasing as individuals neared parturition. This trend was observed in trophic (e.g., Glx, Ala, Val), source (e.g., Lys), and physiological (e.g., Gly) AAs. Several potential mechanisms may explain these results including nitrogen conservation, scavenging, and bacterially mediated breakdown of urea to free ammonia that is used to synthesize AAs. We observed contrasting patterns of isotopic discrimination in embryo tissues, which generally became enriched in 15N throughout development. This was attributed to greater excretion of nitrogenous waste in more developed embryos, and the role of physiologically sensitive AAs (i.e., Gly and Ser) to molecular processes such as nucleotide synthesis. These findings underscore how AA isotopes can quantify shifts in nitrogen balance, providing unequivocal evidence for the role of physiological condition in driving δ15N variation in both bulk tissues and individual AAs. [ABSTRACT FROM AUTHOR]

Animal movement and resource use are essential considerations for effective environmental management, but they are challenging to quantify in expansive natural ecosystems such as oceans.We used a novel combination of fish tracking with expansive acoustic telemetry networks, stable isotope analysis and integrated modelling techniques to characterize the spatial and trophic ecology of a marine fish species, permit Trachinotus falcatus, and to address specific resource management needs in the Florida Keys.Tracking‐based movement patterns indicated that permit remained primarily within the designated fisheries management unit (92% of individuals), but they moved frequently among distinct habitat types and fisheries. Movement metrics from 109 individuals were integrated into Bayesian isotope mixing models, revealing variable reliance on seagrass‐ versus offshore/pelagic‐based energy channels amongst individuals. Variance was driven mainly by fish habitat use and home range size (km2).A telemetry‐based regional isoscape, informed by individual‐level estimates of resource use (% seagrass reliance; median = 70%, 29%–100% range), illustrated connectivity among habitats and fisheries. Specifically, seagrass flats were highly connected with the Florida reef tract, with frequent movements between these habitat types and a high reliance on seagrass‐based prey. There was a distinction between these fish and those occupying artificial reefs, with the latter showing high use of pelagic/offshore (i.e. planktonic) energy channels.Synthesis and applications. This study used a novel combination of telemetry, stable isotope analysis and integrated modelling techniques to identify two distinct ecotypes of a nearshore fish species, permit, in the Florida Keys. Of the two ecotypes, nearshore Florida Keys permit support multiple valuable fisheries; for these fish management should prioritize conservation of seagrass flats as a key permit food source, as well as fisheries protection measures at spawning sites on the Florida reef tract. This study highlights the capacity for integrated telemetry‐isotope models to provide key insights into animal ecology that has direct implications for applied environmental management. [ABSTRACT FROM AUTHOR]

The isotopic composition of tooth‐bound collagen has long been used to reconstruct dietary patterns of animals in extant and palaeoecological systems. For sharks that replace teeth rapidly in a conveyor‐like system, stable isotopes of tooth collagen (δ13CTeeth & δ15NTeeth) are poorly understood and lacking in ecological context relative to other non‐lethally sampled tissues. This tissue holds promise, because shark jaws may preserve isotopic chronologies from which to infer individual‐level ecological patterns across a range of temporal resolutions.Carbon and nitrogen stable isotope values were measured and compared between extracted tooth collagen and four other non‐lethally sampled tissues of varying isotopic turnover rates: blood plasma, red blood cells, fin and muscle, from eight species of sharks. Individual‐level isotopic variability of shark tooth collagen was evaluated by profiling teeth of different ages across whole jaws for the shortfin mako shark Isurus oxyrinchus and sandbar shark Carcharhinus plumbeus.Measurements of δ13CTeeth and δ15NTeeth were positively correlated with isotopic values from the four other tissues. Collagen δ13C was consistently 13C‐enriched relative to all other tissues. Patterns for δ15N were slightly less uniform; tooth collagen was generally 15N‐enriched relative to muscle and red blood cells, but congruent with fin and blood plasma (values clustered around a 1:1 relationship).Significant within‐individual variability was observed across whole shortfin mako shark (δ13C range = 1.4‰, δ15N range = 3.6‰) and sandbar shark (δ13C range = 1.2‰–2.4‰, δ15N range = 1.7‰–2.4‰) jaws, which trended with tooth age.We conclude that amino acid composition and associated patterns of isotopic fractionation result in predictable isotopic offsets between tissues. Within‐individual variability of tooth collagen stable isotope values suggests teeth of different ages may serve as ecological chronologies, that could be applied to studies on migration and individual‐level diet variation across diverse time‐scales. Greater understanding of tooth replacement rates, isotopic turnover and associated fractionation of tooth collagen will help refine potential ecological inferences, outlining clear goals for future scientific inquiry. [ABSTRACT FROM AUTHOR]

Nitrogen stable isotopes (δ15N) are typically used to estimate trophic position, providing insight into ecological roles and broader food web structure. Ecological inferences drawn from these estimates rely on quantification of isotopic baselines, i.e., low trophic level organisms reflecting the predominant nitrogen sources that support food web biomass. When baselines vary due to environmental (e.g., temperature) or anthropogenic factors (e.g., nutrient run-off), interpretation of trophic position based on δ15N may not be ecologically sound. Here, we tested the effects of assuming stable versus spatially variable δ15N baselines used to estimate the trophic position of a cosmopolitan estuarine predator—juvenile bull sharks (Carcharhinus leucas). Sampling across the San Antonio Bay system, TX, USA revealed that baseline consumers exhibited spatially variable δ15N values, which were strongly associated with capture salinity representing the influence of anthropogenically introduced nitrogen largely from fluvial run-off. As a result, estimates of bull shark trophic position differed based on baseline assumptions—sharks exhibited an ontogenetic shift in trophic position when spatial variability of baseline δ15N was accounted for, while an uncorrected approach indicated no relationship between body size and trophic position. Diet data supported ontogenetic shifts in bull shark diets, with increased consumption of larger-bodied prey among older individuals. Evaluation of isotopic baselines in spatially dynamic ecosystems like estuaries is essential, especially for highly mobile species like sharks that traverse dynamic isoscapes. A literature review revealed that only 16% of studies leveraging stable isotopes to assess the trophic ecology of sharks have accounted for potential spatial variability of isotopic baselines. As such, greater consideration of variability in isotopic baselines is important moving forward considering the ubiquitous application of this technique by ecologists. [ABSTRACT FROM AUTHOR]

Over the last century anthropogenic activities have rapidly increased the influx of metals and metalloids entering the marine environment, which can bioaccumulate and biomagnify in marine top consumers. This may elicit sublethal effects on target organisms, having broad implications for human seafood consumers. We provide the first assessment of metal (Cd, Pb, Cr, Mn, Co, Cu, Zn, As, Ag, and THg) and metalloid (As) concentrations in the muscle tissue of coastal sharks from The Bahamas. A total of 36 individual sharks from six species were evaluated, spanning two regions/study areas, with a focus on the Caribbean reef shark (Carcharhinus perezi), and to a lesser extent the tiger shark (Galeocerdo cuvier). This is due their high relative abundance and ecological significance throughout coastal Bahamian and regional ecosystems. Caribbean reef sharks exhibited some of the highest metal concentrations compared to five other species, and peaks in the concentrations of Pb, Cr, Cu were observed as individuals reached sexual maturity. Observations were attributed to foraging on larger, more piscivorous prey, high longevity, as well a potential slowing rate of growth. We observed correlations between some metals, which are challenging to interpret but may be attributed to trophic level and ambient metal conditions. Our results provide the first account of metal concentrations in Bahamian sharks, suggesting individuals exhibit high concentrations which may potentially cause sublethal effects. Finally, these findings underscore the potential toxicity of shark meat and have significant implications for human consumers. [ABSTRACT FROM AUTHOR]

Golden and Blueline Tilefish (Lopholatilus chamaeleonticeps and Caulolatilus microps) are keystone taxa in northwest (NW) Atlantic continental shelf‐edge environments due to their biotic (trophic‐mediated) and abiotic (ecosystem engineering) functional roles combined with high‐value fisheries. Despite this importance, the ecological niche dynamics (i.e., those relating to trophic behavior and food‐web interactions) of these sympatric species are poorly understood, knowledge of which may be consequential for maintaining both ecosystem function and fishery sustainability. We used stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) to build realized ecological niche hypervolumes to serve as proxies for diet and production use patterns of L. chamaeleonticeps and C. microps. We hypothesized that: (a) species exhibit ontogenetic shifts in diet and use of production sources; (b) species acquire energy from spatially distinct resource pools that reflect a sedentary life‐history and differential use of the continental shelf‐edge; and (c) species exhibit differentiation in one or more measured niche axes. We found evidence for ontogenetic shifts in diet (δ15N) but not production source (δ13C) in both species, suggesting a subtle expansion of measured ecological niche axes. Spatial interpolation of stable isotope ratios showed distinct latitudinal gradients; for example, individuals were 13C enriched in northern and 15N enriched in southern regions, supporting the assertion that tilefish species acquire energy from regional resource pools. High isotopic overlap was observed among species (≥82%); however, when hypervolumes included depth and region of capture, overlap among species substantially decreased to overlap estimates of 15%–77%. This suggests that spatial segregation could alleviate potential competition for resources among tilefish species inhabiting continental shelf‐edge environments. Importantly, our results question the consensus interpretation of isotopic overlap estimates as representative of direct competition among species for shared resources or habitats, instead identifying habitat segregation as a possible mechanism for coexistence of tilefish species in the NW Atlantic. [ABSTRACT FROM AUTHOR]

Summary: In drug development, we ask ourselves which population, endpoint and treatment comparison should be investigated. In this context, we also debate what matters most to the different stakeholders that are involved in clinical drug development, for example, patients, physicians, regulators and payers. With the publication of draft ICH E9 addendum on estimands in 2017, we now have a common framework and language to discuss such questions in an informed and transparent way. This has led to the estimand discussion being a key element in study development, including design, analysis and interpretation of a treatment effect. At an invited session at the 2018 PSI annual conference, PSI hosted a role‐play debate where the aim of the session was to mimic a regulatory and payer scientific advice discussion for a COPD drug. Including role‐play views from an industry sponsor, a patient, a regulator and a payer. This paper presents the invented COPD case‐study design and considerations relating to appropriate estimands are discussed by each of the stakeholders from their differing viewpoints with the additional inclusion of a technical (academic) perspective. The rationale for each perspective on approaches for handling intercurrent events is presented, with a key emphasis on the application of while‐on‐treatment and treatment policy estimands in this context. It is increasingly recognised that the treatment effect estimated by the treatment policy approach may not always be of primary clinical interest and may not appropriately communicate to patients the efficacy they can expect if they take the treatment as directed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the effects of high CO2 exposure on wound healing rates in an elasmobranch fish (Urobatis jamaicensis). Small dermal injuries (8 mm biopsy) closed by 22 days post wounding with a decrease in haematocrit. High CO2 exposure (ΔpH = 1.4) did not influence healing rate or haematocrit. Combined, these data provide evidence that minimally invasive scientific procedures have short‐term impacts on elasmobranch fishes even during exposure to a chronic stressor. Therefore, wound healing rates may not be strongly impacted by ocean acidification (ΔpH = 0.4). [ABSTRACT FROM AUTHOR]

The development of the isotopic niche, an n-dimensional hypervolume (with n being the number of isotopes) occupied by a population in delta space, has revolutionized the study of animal interactions in wild populations. While the isotopic niche offers a useful means to understand interactions at many ecological resolutions (e.g., individual, population, community, ecosystem), a variety of intrinsic and extrinsic factors drive isotopic variability and influence the ultimate geometry of observed niche dimensions. Here, we provide an updated synthesis to guide the application of bulk stable isotope ratios to study ecological niches. We summarize progress in the application of bulk stable isotope ratios for evaluating niches to synthesize a formal definition of the isotopic niche. We identify six broad categories to describe drivers of isotopic variance introduced by the animal, its environment, and the researcher, and provide recommendations to account for such variations before, during, and after sample collection and data analyses. Our synthesis illustrates the considerations that should be made before employing the isotopic niche to broader ecological contexts, and offers guidance for the use and interpretation of isotopic niche dynamics in future studies. [ABSTRACT FROM AUTHOR]

Calculation of dietary niche characteristics using stable isotopes has become a popular approach to understand the functional role of taxa across food webs. An underlying assumption of this approach is that stable isotopes accurately reflect the dietary breadth of a species over a temporal duration defined by tissue-specific isotopic turnover rates. In theory, dietary niche estimates derived from fast turnover rate tissues (e.g., blood plasma and liver) may augment stomach content-derived estimates more agreeably than slower turnover rate tissues (e.g., muscle or fin). We tested this hypothesis by comparing commonly used dietary niche estimates derived from stomach contents (nicheSCA: Levins', Shannon–Wiener's, and Smith's), with those estimated using stable isotopes [nicheSIA: standard ellipse area (SEA), convex hull total area (TA), theta (θ), and ellipse eccentricity (E)] of liver and muscle tissue. Model species were three large-bodied sharks: white (Carcharodon carcharias), dusky (Carcharhinus obscurus), and scalloped hammerhead (Sphyrna lewini). Within-technique comparisons for nicheSCA and nicheSIA metrics (i.e., SEA vs. TA) were often correlated; however, we did not observe any statistically significant correlations between nicheSCA and liver/muscle tissue nicheSIA (i.e., Levins' vs. SEA). We conclude that nicheSCA and nicheSIA do not provide comparable estimates of dietary niche, at least for the three predator species examined. This fundamental discrepancy highlights technique-specific limitations to estimating organismal dietary niche and identifies a need for the use of clearly defined niche metrics, i.e., the standardized use and reporting of the term isotopic niche as proposed by Newsome et al. (Front Ecol Environ 5:429–436, 2007). Finally, further investigation into the factors underpinning nicheSIA is required to better contextualize this popular ecological metric when compared to nicheSCA. [ABSTRACT FROM AUTHOR]

Recent studies on shark assemblages on the northeast Florida and southeast Georgia coast (hereafter referred to collectively as the "First Coast") have demonstrated differences in species and age‐class composition of catch from previously characterized estuaries and newly surveyed area beaches, demonstrating that these regions may provide a critical habitat to different segments (i.e., life stages) of local shark populations. In this study, carbon and nitrogen stable isotopes (δ13C and δ15N) from muscle tissue and blood plasma were used to examine trophic dynamics (and temporal variability thereof) of the three dominant co‐occurring species found along First Coast beaches (the Atlantic Sharpnose shark Rhizoprionodon terraenovae, Blacknose shark Carcharhinus acronotus and Blacktip shark Carcharhinus limbatus) to determine if they exhibit overlap in resource use along with spatial and temporal habitat use. Although considered spatially segregated from the beach species, a dominant, age‐class species found in First Coast estuaries (juvenile Sandbar sharks Carcharhinus plumbeus) was also included in this analysis for comparison. Temporal variability of resource‐use characteristics was detected at the species level. Resource‐use overlap among species varied by tissue type and was generally higher for blood plasma, suggesting greater resource sharing over more recent time periods. Over longer time periods Atlantic Sharpnose and Blacktip sharks exhibited resource‐use expansion, whereas Blacknose sharks exhibited a narrowing in resource use, suggesting a more specialized foraging strategy compared to the other species. The resource‐use breadth of Sandbar sharks also expanded between blood plasma and muscle tissue. Significant size relationships were detected in Blacktip and Sandbar sharks, indicating ontogenetic resource shifts for both species. A diversity of highly productive resource pools likely support shark populations along the First Coast such that resource‐use differentiation is not required to facilitate species co‐occurrence. This work may shed light on understanding patterns of species co‐occurrence as well as aid in future conservation efforts. [ABSTRACT FROM AUTHOR]

We evaluated whether existing assumptions regarding the trophic ecology of a poorly‐studied predator guild, northwest (NW) Atlantic skates (family: Rajidae), were supported across broad geographic scales. Four hypotheses were tested using carbon (δ13C) and nitrogen (δ15N) stable isotope values as a proxy for foraging behavior: 1) species exhibit ontogenetic shifts in habitat and thus display a shift in 13C with differential use of the continental shelf; 2) species exhibit ontogenetic prey shifts (i.e. from smaller to larger prey items) and become enriched in 15N; 3) individuals acquire energy from spatially confined local resource pools and exhibit limited displacement; and 4) species exhibit similarly sized and highly overlapping trophic niches. We found some evidence for ontogenetic shifts in habitat‐use (δ13C) for thorny and little skate and diet (δ15N) of thorny and winter skate and hypothesize that individuals exhibit gradual trophic niche transition, especially in δ15N space, rather than a clear and distinct shift in diet throughout ontogeny. Spatial isoscapes generated for little, thorny, and winter skate highlighted distinct spatial patterns in isotopic composition across the coastal shelf. For little and thorny skate, patterns mimicked expected spatial variability in the isotopic composition of phytoplankton/POM, suggesting limited displacement and utilization of spatially confined resource pools. Winter skate, however, exhibited a much narrower range of δ13C and δ15N values, suggesting individuals may use resources from a more confined latitudinal range. Although high total trophic niche overlap was observed between some species (e.g. little and thorny skate), sympatric species (e.g. little and winter skate) exhibited a degree of trophic niche separation. These findings offer new insight into the trophic dynamics of a poorly‐studied, vulnerable group of predators, and highlight a need to re‐examine assumptions pertaining to aspects of their ecology. [ABSTRACT FROM AUTHOR]

Skates (class Chondrichthyes; subclass Elasmobranchii; order Rajiformes; family Rajidae) comprise one quarter of extant chondrichthyans, yet have received little attention in the scientific literature likely due to their relatively low economic value and difficulties in species identification. The absence of species‐specific information on catch, life history and migration of skates has often precluded the development of single‐species stock assessments and led to the use of cursory multispecies assessments, which lack the ability to track species‐specific catch and abundance trends. This has resulted in undetected local extirpations, as has been previously reported for common (Dipturus batis, Rajidae), white (Rostroraja alba, Rajidae) and long‐nose (Dipturus oxyrhinchus, Rajidae) skates in the Irish Sea. Here, we (a) use case studies to illustrate how the perception of skate population structure and stock status has historically been masked through multispecies assessment and management practices, (b) review current information on the movement of skates and identify gaps in knowledge, and (c) identify biases associated with the use of various tagging technologies, which have confounded our understanding of movement and migration ecology of skates. Considering that over 40% of extant Rajidae species are listed as "Data Deficient" by the International Union for Conservation of Nature, we illustrate a critical need to broaden the current understanding of skate life history, movement and migration ecology by providing recommendations on the further application of electronic tags and biogeochemical natural tags in movement studies and highlight the benefits that studies using these approaches have for novel management frameworks. [ABSTRACT FROM AUTHOR]

Fraud/cheat in the buying and selling of commodities is part and parcel of modern businesses worldwide, and a common phenomenon in Nigeria. Personal purchases of meats using a measurement scale and others without measurement scale were made in Abakiliki and Calabar meat markets. Empirically, holding the quality of meats constant, a paired t-test analytical tool shows significant difference in the weight of meats bought and sold by non-measurement scale and those with measurement scale. Theoretically, perspectives from rational choice, fraud triangle, economic, social learning/contagious, anomie theories and political economy are drawn on to suggest an integrated multiple reinforcing-social-forces theory of fraud in the sale of meats. Results confirm that consumers receive less value for their money when they purchase meats without metrology. Cheat is conceived as a product of individual, structural variables and process that interact at different levels to produce negative consequences. An EpiCrim approach which, include strategies to promote consumers' rights awareness, impose sanctions with certainty, celerity and pains, and other measures to assist helpless victims of cheat is advocated. [ABSTRACT FROM AUTHOR]

Summary: The draft addendum to the ICH E9 regulatory guideline asks for explicit definition of the treatment effect to be estimated in clinical trials. The draft guideline also introduces the concept of intercurrent events to describe events that occur post‐randomisation that may affect efficacy assessment. Composite estimands allow incorporation of intercurrent events in the definition of the endpoint. A common example of an intercurrent event is discontinuation of randomised treatment and use of a composite strategy would assess treatment effect based on a variable that combines the outcome variable of interest with discontinuation of randomised treatment. Use of a composite estimand may avoid the need for imputation which would be required by a treatment policy estimand. The draft guideline gives the example of a binary approach for specifying a composite estimand. When the variable is measured on a non‐binary scale, other options are available where the intercurrent event is given an extreme unfavourable value, for example comparison of median values or analysis based on categories of response. This paper reviews approaches to deriving a composite estimand and contrasts the use of this estimand to the treatment policy estimand. The benefits of using each strategy are discussed and examples of the use of the different approaches are given for a clinical trial in nasal polyposis and a steroid reduction trial in severe asthma. [ABSTRACT FROM AUTHOR]

Background: In the United States, young men who have sex with men (YMSM) of color represent a high number of new HIV diagnoses annually. HIV pre-exposure prophylaxis (PrEP) is effective and acceptable to YMSM of color; yet, PrEP uptake is low in those communities because of barriers including stigma, cost, adherence concerns, and medical distrust. A telehealth-based approach to PrEP initiation may be a solution to those barriers. This pilot study investigates one such intervention called PrEPTECH. Methods: We enrolled 25 HIV-uninfected YMSM, aged 18–25 years, from the San Francisco Bay Area into a 180-day longitudinal study between November 2016 and May 2017. Participants received cost-free PrEP services through telehealth [eg, telemedicine visits, home delivery of Truvada, and sexually transmitted infection testing kits], except for 2 laboratory visits. Online survey assessments querying PrEPTECH features and experiences were administered to participants at 90 and 180 days. Results: Eighty-four percent of participants were YMSM of color. Among the 21 who completed the study, 11 of the 16 who wanted to continue PrEP were transitioned to sustainable PrEP providers. At least 75% felt that PrEPTECH was confidential, fast, convenient, and easy to use. Less than 15% personally experienced PrEP stigma during the study. The median time to PrEP initiation was 46 days. Sexually transmitted infection positivity was 20% and 19% at baseline and 90 days, respectively. No HIV infections were detected. Conclusions: Telehealth programs such as PrEPTECH increase PrEP access for YMSM of color by eliminating barriers inherent in traditional clinic-based models. [ABSTRACT FROM AUTHOR]

Lipids affect stable isotope values generated for marine fishes, however these effects remain poorly described for many extant shark taxa, especially deep-sea species. Here, we report the effects of lipid extraction (LE) on δ 13 C, δ 15 N, and C:N values of seven deep-sea sharks, generate novel mathematical normalizations for δ 13 C based on the relationship between bulk and lipid extracted values (δ 13 C Bulk and δ 13 C LE ) and examine whether common normalized correction models provide a robust method for addressing lipid-biasing effects in two species, the Cuban dogfish ( Squalus cubensis ; n = 20), and Greenland shark ( Somniosus microcephalus ; n = 24). LE generally resulted in enrichment of 13 C and 15 N, but produced variable effects on C:N across all species. Novel mathematical normalizations for δ 13 C were derived from the pooled shark community, and a single species-specific correction was generated for the Cuban dogfish, but could not be determined for the Greenland shark. Four common lipid correction models used for teleosts, failed to accurately predict δ 13 C values statistically similar to δ 13 C LE , in both Cuban dogfish and Greenland sharks, likely due to the confounding effects of lipids and urea on C:N. These observations suggest that chemical lipid extraction should be a mandatory procedure prior to interpreting stable isotope data for deep-sea sharks, at least for those species where lipid effects are large. [ABSTRACT FROM AUTHOR]

Acquiring movement data for small-bodied, deep-water chondrichthyans is challenged by extreme effects of capture and handling stress, and post-release predation, however, it is urgently required to examine important fisheries interactions and assess the ecological role of these species within deep-water food webs. Here we suggest a novel release-cage mechanism to deploy pop-up satellite archival tags, as well as present vertical habitat data for a data-deficient, small-bodied, deep-water bycatch species, the Cuban dogfish ( Squalus cubensis ). Data were gathered from seven of eight High Rate X-Tags deployed on mature Cuban dogfish in the Exuma Sound, The Bahamas. Recovery periods appeared variable between individuals and are likely driven by capture-and-handling stress and tag burden. Application of the cross-correlation function to time-series depth and temperature data indicated three of the seven individuals suffered mortality through predation, which occurred during daytime, and suggests Cuban dogfish may constitute a proportion of deep-water apex predator diet in the Exuma Sound. Two animals were successfully released via a novel release-cage mechanism and displayed either no, or rapid (<15 mins) vertically stationary recovery periods and were not consumed by predators; data for these individuals were recorded for the entire deployment duration (14 days). Vertical habitat data suggests Cuban dogfish are diel-vertical migrators, similar to other deep-water taxa, and exhibit a relatively broad temperature and depth range, which may be driven by preference for specific bathymetric structures. These techniques provide an important first step into acquiring and presenting vertical habitat data for small-bodied, deep-water chondrichthyans, which can be directly applied to fisheries and ecosystem-based management approaches. [ABSTRACT FROM AUTHOR]

From 1929 to 1941, the Vrbas Banate was one of nine provinces of the Kingdom Yugoslavia, and according to historical data, the poorest one, without well-organized and sustainable agriculture production. Naturalistic production and poor animal health control in the Vrbas Banate were the most important risk factors for infectious disease spreading. Anthrax was very prevalent infectious disease in domestic animals and humans in that period, but some data on this disease remain scarce. In this paper epidemiology and clinical investigation of anthrax in the Vrbas Banate are reviewed. Apart from many aggravating factors that influenced the control of anthrax, the veterinary service of Banate contributed to the development of animal husbandry, animal health and public health in that period. [ABSTRACT FROM AUTHOR]

ABSTRACT Optimizing the productivity of nonconventional, low-permeability 'shale' reservoirs requires detailed knowledge of the mechanical properties of such materials. These rocks' elastic anisotropy is acknowledged but usually ignored due to difficulties in obtaining such information. Here we study in detail the dynamic and static elastic properties of a suite of calcareous mudstones from the nonconventional Duvernay reservoir of Alberta, Canada. The complete set of transversely isotropic elastic constants is obtained from strategically oriented ultrasonic transducers to confining pressures of 90 MPa. Wave speed anisotropies of up to 35% are observed at even the highest confining pressures. Furthermore, the stress sensitivity of the wave speeds, and hence moduli, is itself highly dependent on direction with speeds taken perpendicular to the bedding plane being highly nonlinearly dependent on pressure, whereas those along the bedding plane show, unexpectedly, nearly no pressure dependence. These observations are in qualitative agreement with the preferentially oriented porosity and minerals seen in scanning electron microscope images. These results may be significant to the interpretation of sonic logs and azimuthal amplitude versus offset for principal stress directions, for the concentration of stress within such formations, and for estimation of static engineering moduli from sonic log wave speeds. [ABSTRACT FROM AUTHOR]

Rivers can transport a substantial amount of allochthonous nutrients into coastal marine ecosystems. These nutrients are a significant contributor to estuarine productivity, resulting in increased fishery production. However, for migratory marine predators, the importance of nutrients from fluvial-dominated estuaries is unclear. We used carbon (δ 13C) and sulfur (δ 34S) stable isotope mixing models to identify the contribution of prey sources in fluvial-dominated estuarine habitat relative to nearby seagrass and offshore reef habitats to five species of migratory shark: finetooth shark Carcharhinus isodon , blacktip shark Carcharhinus limbatus , bull shark Carcharhinus leucas, Atlantic sharpnose shark Rhizoprionodon terraenovae , and bonnethead shark Sphyrna tiburo. We explored how the contribution of these sources varied as a function of shark length. Sharks generally exhibited a strong reliance on prey from fluvial-estuarine energy channels, with the youngest individuals displaying the highest reliance relative to larger individuals. Models suggested that sharks rely increasingly on nutrient sources from nearby seagrass or offshore reef habitats with age, potentially acting as vectors of nutrient transport across systems. These findings illustrate the importance of a fluvial-dominated estuarine system to migratory marine predators and suggest that these individuals may connect inshore and offshore food-webs. Estuarine systems with high fluvial-influence offer important nutrient subsidies for migratory species, which can transport that energy to adjacent, nutrient-limited systems. Changes to river-flow regimes could disrupt the channeling of nutrients to coastal marine systems, affecting migratory predator populations and their role in transporting these nutrients across the seascape. • Stable isotope analyses revealed that coastal sharks use multiple distinct energy channels. • 52 – 79% of modeled shark diet came from intermittent use of a river-dominated estuary with high fluvial input. • We observed significant ontogenetic shifts in shark diet from fluvial nutrients to seagrass and/or offshore nutrients. [ABSTRACT FROM AUTHOR]

The management of migratory taxa relies on the knowledge of their movements. Among them, ontogenetic habitat shift, from nurseries to adult habitats, is a behavioural trait shared across marine taxa allowing resource partitioning between life stages and reducing predation risk. As this movement is consistent over time, characterizing its timing is critical to implement efficient management plans, notably in coastal areas to mitigate the impact of fisheries on juvenile stocks.In the Mexican Pacific, habitat use of the smooth hammerhead shark (Sphyrna zygaena) is poorly described, while the species is heavily harvested. Given the large uncertainties associated with the timing of out‐migration from coastal nursery grounds to offshore waters prior to reproductive maturity, a more precise assessment of smooth hammerhead shark movements is needed.Photochemical degradation of mercury imparts mass‐independent isotope fractionation (Δ199Hg) which can be used to discriminate between neonate coastal shallow habitats and the offshore deep foraging patterns of late juveniles. Here, we present the application of muscle Δ199Hg as molecular clocks to predict the timing of ontogenetic habitat shifts by smooth hammerhead sharks, based on their isotopic compositions at the initial and arrival habitats and on muscle isotopic turnover rate.We observed decreases in Δ199Hg values with shark body length, reflecting increasing reliance on offshore mesopelagic prey with age. Coastal residency estimates indicated that smooth hammerhead sharks utilize coastal resources for 2 years prior to offshore migration, suggesting a prolonged residency in these ecosystems.Policy implications. This study demonstrates how mercury stable isotopes and isotopic clocks can be implemented as a complementary tool for stock management by predicting the timing of animal migration—a key aspect in the conservation of marine taxa. In the Mexican Pacific, fishing pressure on shark species occurs in coastal habitats depleting juvenile stocks. Consequently, management decision support tools are imperative for effectively maintaining early life stage population levels over time. The finding that smooth hammerhead sharks extensively rely on highly fished habitats for 2 years after parturition supports the relevance of establishing a size limit in coastal fisheries and demonstrates how the current temporal shark fishing closure could lack efficiency for the species. [ABSTRACT FROM AUTHOR]

We present the results from the RHOMA2011-LEG2 campaign that took place in the eastern Gulf of Lion from 7 to 17 Oct 2011 and combine them with remote sensing observations and results from a 3D coupled hydrodynamic-biogeochemical model to study an intrusion event of the Northern Current (NC) onto the continental shelf in the Gulf of Lion (NW Mediterranean). Our analysis shows that during the intrusion, the previously upwelled nutrient-rich water present on the shelf is replaced by warmer and mostly oligotrophic NC water within a matter of 2–3 days. This has a marked impact on the local biogeochemistry in the Gulf with pre-intrusion Chl- a concentrations in the surface layer of over 0.5 mg m −3 dropping to near the detection limit within less than 72 h. The intrusion event leads to a dramatic albeit short-lived regime shift in the limiting nutrient for primary production: prior to the intrusion most of production on the shelf is nitrogen limited while the intrusion induces a shift to phosphorous limitation. The relatively high frequency of occurrence of these intrusions in combination with their impact on the local ecosystem make them primary targets for future study. [ABSTRACT FROM AUTHOR]

Purpose: To compare retinal vascular dynamics during acute hyperglycaemia in patients with type 2 diabetes and healthy volunteers. Methods: Twenty-one patients with type 2 diabetes and 27 healthy controls were examined with fundus photographic measurement of retinal vessel diameters, retinal oximetry, macular perfusion velocities and optical coherence tomographic measurement of subfoveal choroidal thickness every 30 min during a 3-hr 75 g oral glucose tolerance test (OGTT). Patients paused antidiabetic therapy for 1 week prior to the OGTT. Results: Plasma glucose (PG) and fluctuations in PG were larger in patients with diabetes (p < 0.0001). PG increased significantly 30 min after ingestion of glucose (p < 0.0001 in both groups). With a delay of 0-120 min, the PG increase was followed by increased retinal arterial oxygen saturations and arteriovenous oxygen saturation differences, narrowed retinal veins and increased arteriovenous diameter ratios.Noeffect of age, gender or diabetes status was observed. Choroidal thickness was transiently reduced in controls and unchanged in patients with diabetes (p = 0.021). Macular perfusion velocities increased after 150 min in patients with diabetes but not in controls (arterial p = 0.059; venous p = 0.16). Higher age and diabetes tended to be associated with higher retinal arterial oxygen saturation. Conclusion: The transition from fasting to acute hyperglycaemia is followed, with a delay of up to 2 hr, by retinal vascular changes, notably increased oxygen extraction, suggesting an effect of secondary metabolic changes. Retinal responses were similar in patients with type 2 diabetes and controls despite differences in glucose levels. It is necessary to standardize measurement conditions in studies of retinal physiology. [ABSTRACT FROM AUTHOR]

Ketone measurement is advocated for the diagnosis of diabetic ketoacidosis and assessment of its severity. Assessing the evidence base for ketone measurement in clinical practice is challenging because multiple methods are available but there is a lack of consensus about which is preferable. Evaluating the utility of ketone measurement is additionally problematic because of variability in the biochemical definition of ketoacidosis internationally and in the proposed thresholds for ketone measures. This has led to conflicting guidance from expert bodies on how ketone measurement should be used in the management of ketoacidosis. The development of point-of-care devices that can reliably measure the capillary blood ketone β-hydroxybutyrate ( BOHB) has widened the spectrum of applications of ketone measurement, but whether the evidence base supporting these applications is robust enough to warrant their incorporation into routine clinical practice remains unclear. The imprecision of capillary blood ketone measures at higher values, the lack of availability of routine laboratory-based assays for BOHB and the continued cost-effectiveness of urine ketone assessment prompt further discussion on the role of capillary blood ketone assessment in ketoacidosis. In the present article, we review the various existing methods of ketone measurement, the precision of capillary blood ketone as compared with other measures, its diagnostic accuracy in predicting ketoacidosis and other clinical applications including prevention, assessment of severity and resolution of ketoacidosis. [ABSTRACT FROM AUTHOR]

Statistical analyses of recurrent event data have typically been based on the missing at random assumption. One implication of this is that, if data are collected only when patients are on their randomized treatment, the resulting de jure estimator of treatment effect corresponds to the situation in which the patients adhere to this regime throughout the study. For confirmatory analysis of clinical trials, sensitivity analyses are required to investigate alternative de facto estimands that depart from this assumption. Recent publications have described the use of multiple imputation methods based on pattern mixture models for continuous outcomes, where imputation for the missing data for one treatment arm (e.g. the active arm) is based on the statistical behaviour of outcomes in another arm (e.g. the placebo arm). This has been referred to as controlled imputation or reference-based imputation. In this paper, we use the negative multinomial distribution to apply this approach to analyses of recurrent events and other similar outcomes. The methods are illustrated by a trial in severe asthma where the primary endpoint was rate of exacerbations and the primary analysis was based on the negative binomial model. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This article discusses how to diagnose and manage patients with ketosis prone type 2 diabetes [ABSTRACT FROM AUTHOR]

Aims: To establish the knowledge of women with pre-gestational diabetes about of the risks of diabetes in pregnancy, and investigate their pregnancy plans, contraceptive choices, and preparedness for pregnancy.Methods: Women of reproductive age attending diabetes clinics across a single busy metropolitan NHS Trust were invited to fill in a questionnaire about pregnancy and contraception. The electronic health records of those women were also reviewed.Results: Ninety-six women completed the questionnaire. The majority of respondents (94%) had Type 1 Diabetes. Only 3% of women met the criteria of 'prepared for pregnancy'. Low efficacy contraception was used by 32% of women. Most women were only aware of a few risks to the mother and fetus in pregnancy, though the majority of women were aware of the importance of good glycaemic control before pregnancy. Previous pregnancies, or attendance at pre-conception counselling, did not improve participant knowledge.Conclusions: Many women with diabetes of reproductive age are poorly prepared for pregnancy, but many are also using less effective contraceptive methods. These areas should be addressed if the poor pregnancy outcome in women with diabetes are to be improved, possibly through the development of an evidenced-based structured education course to target pre-conception and contraception. [ABSTRACT FROM AUTHOR]

Abstract: Three free water surface constructed wetlands (FWSCWs) have been built in the border of the Lake L’Albufera de Valencia (Valencia, Spain). This lake is the emblematic element of one of the most important wetlands in Spain, L’Albufera de Valencia Natural Park, and it is highly eutrophicated. The function of the set of CWs (9ha) is treating the eutrophic water from the lake with the objective of reducing the phytoplankton population and nutrients. The treatment wetlands named as FG and fp are comprised of three basins in a series, while the last, F4, consists of a single cell. During the first 2 years of operation, the inflow from lake was gradually increased from 0.01m3 s−1 (April 2009) to 0.13m3 s−1 (December 2010) with the goal of establishing the maximum hydraulic loading rate (HLR) and finding the highest removal efficiency. Input concentrations of different water quality variables studied showed a high variability. The inflow contained 8.80–94mgl−1 TSS, 0.16–1.13mgl−1 TP, 1–17.30mgl−1 TN, 0.13–13.10mg Nl−1 DIN, 0.10–11.50mg NO3 −-Nl−1, and 3.34–257.03μgl−1 Chl a. The best removal results for these parameters were obtained in the FG wetland, where the average mass removal efficiencies were 75% TSS, 65% TP, 52% TN, 61% DIN, 58% NO3 −-N, and 46% Chl a. In the set of constructed wetlands the removal rates increased with the hydraulic load rate for TSS and TP but neither for nitrogen species nor Chl a; for these variables the input concentrations are a key factor in removal. For instance, mean removal rate for nitrate is 101mg Nm−2 d−1 but values higher than 400mg Nm−2 d−1 were obtained when input concentrations were about 7mg NO3 −-Nl−1. Values of first-order constant aerial rate (k A) have been obtained for all variables. The corresponding values for nitrogen species and total phosphorus are higher than obtained in previous studies but the value k A value for TSS is low (94.9myear−1) owing to the eutrophic characteristics of water and a k A value for phytoplankton-Chl a of 65.1myear−1 is introduced. The management of CWs implies the harvest of vegetation, not for remove nitrogen because nitrification–denitrification processes reduce the 83.3% of TN that enters, but for the phosphorus, limiting nutrient in the Lake L’Albufera, that now is accumulated in plants and soils but could be sent back in several years. [Copyright &y& Elsevier]

Background: Combined lateral elbow tendinosis (tennis elbow) and medial elbow tendinosis (golfer’s elbow) can be a disabling condition that, if unresponsive to nonoperative treatments, may be effectively treated surgically. The authors are not aware of any study that reports the outcome of a combined operation for lateral and medial elbow tendinosis (country club elbow) performed in the same operative setting.Hypothesis: Combined surgical treatment of country club elbow in the same operative setting has similar outcomes to those seen in the literature for single operative procedures.Study Design: Case series; Level of evidence 4.Methods: Outcome measurements included the Numeric Pain Intensity Scale, the Nirschl tennis elbow scoring system, and the American Shoulder and Elbow Surgeons elbow form. Forty-eight patients (53 clinical elbows) were available by telephone, with a minimum time to follow-up of 5 years (range, 5-19 years; mean, 11.7 years).Results: The average Nirschl tennis elbow score improved from 16.7 preoperatively to 70.8 postoperatively (P < .01). The average American Shoulder and Elbow Surgeons elbow score improved from 45.2 to 90.4 (P < .01). The Numeric Pain Intensity Scale score improved from 8.8 to 1.7 (P < .01). By the criteria of the Nirschl tennis elbow score, results were rated excellent in 38 elbows, good in 7 elbows, fair in 5 elbows, and poor in 3 elbows, with 85% (45 of 53) good to excellent results. Patient satisfaction with the surgery averaged 8.7 out of 10. Of the 46 patients who played sports, 44 (96%) reported returning to their sports.Conclusion: When nonoperative treatment of lateral and medial elbow tendinosis fails, combined surgical intervention via the Nirschl operative techniques for country club elbow is highly effective, with results similar to those of single-sided intervention. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is of particular interest to anaesthetists because of the muscle groups affected, the pharmacology of the neuromuscular junction, and interaction of both the disease and treatment with many anaesthetic drugs. Anaesthetists may encounter children with myasthenia either to facilitate treatment options or to institute mechanical ventilation in the face of a crisis. This paper reviews the literature pertaining to the pathophysiology and applied pharmacology of the disease and explores the relationship between these and the anaesthetic management. In addition to illustrating the tried-and-tested techniques, some newer management options are explored. [ABSTRACT FROM AUTHOR]

Background: Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. Nϵ-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. Nϵ-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors. Principal Findings: High-throughput screening of a ∼236,000-member collection of diverse molecules arrayed as dilution series was used to identify inhibitors of the JMJD2 (KDM4) family of 2-oxoglutarate-dependent histone demethylases. Initial screening hits were prioritized by a combination of cheminformatics, counterscreening using a coupled assay enzyme, and orthogonal confirmatory detection of inhibition by mass spectrometric assays. Follow-up studies were carried out on one of the series identified, 8-hydroxyquinolines, which were shown by crystallographic analyses to inhibit by binding to the active site Fe(II) and to modulate demethylation at the H3K9 locus in a cell-based assay. Conclusions: These studies demonstrate that diverse compound screening can yield novel inhibitors of 2OG dependent histone demethylases and provide starting points for the development of potent and selective agents to interrogate epigenetic regulation. [ABSTRACT FROM AUTHOR]

Direct velocity feedback control of structures is well known to increase structural damping and thus reduce vibration. In multi-channel systems the way in which the velocity signals are used to inform the actuators ranges from decentralized control, through distributed or clustered control to fully centralized control. The objective of distributed controllers is to exploit the anticipated performance advantage of the centralized control while maintaining the scalability, ease of implementation, and robustness of decentralized control. However, and in seeming contradiction, some investigations have concluded that decentralized control performs as well as distributed and centralized control, while other results have indicated that distributed control has significant performance advantages over decentralized control. The purpose of this work is to explain this seeming contradiction in results, to explore the effectiveness of decentralized, distributed, and centralized vibro-acoustic control, and to expand the concept of distributed control to include the distribution of the optimization process and the cost function employed. [ABSTRACT FROM AUTHOR]

Aims To assess efficacy of conservative management of neuropathic forefoot ulcers with underlying osteomyelitis in subjects with diabetes when magnetic resonance imaging (MRI) is used to confirm or establish diagnosis and to guide antibiotic duration. Methods A retrospective cohort study over 6 years assessing rates of ulcer healing, relapse and amputation. Antibiotics were continued for 3-month cycles with interval MRI: if the lesion had healed and bone signal change resolved or improved, antibiotics were discontinued; if the lesion had not healed or there was no difference in bone signal change, antibiotics were continued for a further 3-month cycle; clinical or radiological deterioration resulted in endoluminal or open vascular surgical intervention where appropriate, or digital or more proximal amputation. Results There were 53 episodes in 47 subjects (mean ± sd age 62 ± 13 years, duration of diabetes 19 ± 13 years, glycated haemoglobin 8.4 ± 1.6%; six with Type 1 diabetes and seven with end-stage renal failure). Successful healing without relapse was achieved in 40 episodes (75%) [median (range) duration of antibiotics 6 (3–12) months and follow-up post-cessation of antibiotics 15 (3–58) months]. Relapse occurred in six episodes (13%) at 31 (2–38) months post-cessation of antibiotics. There were one major (2%) and eight minor (15%) amputations. Five subjects have died (11%), all without foot ulcers. Conclusions High rates of healing and low rates of amputation were achieved. The use of MRI was associated with long courses of antibiotics, but particularly low relapse rate. [ABSTRACT FROM AUTHOR]

Abstract: Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modern positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use. [Copyright &y& Elsevier]

Glucose monitoring technology has been used in the management of diabetes for three decades. Traditional devices use enzymatic methods to measure glucose concentration and provide point sample information. More recently continuous glucose monitoring devices have become available providing more detailed data on glucose excursions. In future applications the continuous glucose sensor may become a critical component of the closed loop insulin delivery system and, as such, must be selective, rapid, predictable and acceptable for continuous patient use. Many potential sensing modalities are being pursued including optical and transdermal techniques. This review aims to summarize existing technology, the methods for assessing glucose sensing devices and provide an overview of emergent sensing modalities. [ABSTRACT FROM AUTHOR]

What's new?: Chronic sleep disturbance is common for people with Type 1 diabetes.Fear of nocturnal hypoglycaemia is causing frequent nocturnal blood glucose testing causing impaired sleep.New strategies for the prevention of nocturnal hypoglycaemia need to be devised and tested.The consequences of chronic sleep disturbance for people living with diabetes and their families needs to be appreciated by their clinical advisors. [ABSTRACT FROM AUTHOR]

For many years there has been a consensus among the Clinical Research community that ITT analysis represents the correct approach for the vast majority of trials. Recent worldwide regulatory guidance for pharmaceutical industry trials has allowed discussion of alternatives to the ITT approach to analysis; different treatment effects can be considered which may be more clinically meaningful and more relevant to patients and prescribers. The key concept is of a trial "estimand", a precise description of the estimated treatment effect. The strategy chosen to account for patients who discontinue treatment or take alternative medications which are not part of the randomised treatment regimen are important determinants of this treatment effect. One strategy to account for these events is treatment policy, which corresponds to an ITT approach. Alternative equally valid strategies address what the treatment effect is if the patient actually takes the treatment or does not use specific alternative medication. There is no single right answer to which strategy is most appropriate, the solution depends on the key clinical question of interest. The estimands framework discussed in the new guidance has been particularly useful in the context of the current COVID-19 pandemic and has clarified what choices are available to account for the impact of COVID-19 on clinical trials. Specifically, an ITT approach addresses a treatment effect that may not be generalisable beyond the current pandemic. [ABSTRACT FROM AUTHOR]