Search

Background: Percutaneous Zadek osteotomy (ZO) has emerged as a surgical treatment of insertional Achilles tendinopathy (IAT) over the last decade. Existing literature is limited regarding the comparison of this approach with the more established, open ZO technique. This systematic review aims to evaluate and compare the current data on open vs percutaneous ZO approaches to help set evidence-based guidelines. Methods: A systematic literature search was performed using the keywords (Zadek osteotomy) OR (Keck and Kelly osteotomy) OR (dorsal closing wedge calcaneal osteotomy) OR (Haglund Deformity) OR (Haglund Syndrome) OR (Insertional Achilles Tendinopathy) and MeSH terms Osteotomy , Calcaneus , Syndrome , Insertional , Achilles tendon , and Tendinopathy . Our search included the following databases: PubMed, Embase, and the Cochrane Library. The PRISMA protocol and the Cochrane Handbook guidelines were followed. All studies included were published from 2009 to 2024 and included the use of open or percutaneous approaches of ZO for the treatment of IAT with at least a 12-month follow-up. The MINORS score criteria were used to evaluate the strength and quality of studies. Results: A total of 17 studies were reviewed, including 611 subjects and 625 ZO procedures. Of these procedures, 81 (11%) subjects had a percutaneous and 544 (89%) subjects had an open ZO. The mean follow-up time was 16.1 months for patients treated with percutaneous ZO and 36.1 months for patients treated with open ZO. Both open and percutaneous studies included in this review showed postoperative improvements in AOFAS, FFI, VISA-A, and VAS scores in patients with IAT. The reported complication rate was 5.8% among patients treated with percutaneous ZO and 10.2% among patients treated with open ZO. Conclusion: Percutaneous ZO is an emerging approach with substantially fewer documented cases compared with the open ZO. Both percutaneous and open ZO appear to be relatively effective treatments for insertional Achilles tendinopathy with Haglund’s deformity. The lower complication rates reported for percutaneous ZO is encouraging. Further investigation with more subjects undergoing percutaneous ZO is clearly needed.

Stable isotope data have made pivotal contributions to nearly every discipline of the physical and natural sciences. As the generation and application of stable isotope data continues to grow exponentially, so does the need for a unifying data repository to improve accessibility and promote collaborative engagement. This paper provides an overview of the design, development, and implementation of IsoBank (www.isobank.org), a community-driven initiative to create an open-access repository for stable isotope data implemented online in 2021. A central goal of IsoBank is to provide a web-accessible database supporting interdisciplinary stable isotope research and educational opportunities. To achieve this goal, we convened a multi-disciplinary group of over 40 analytical experts, stable isotope researchers, database managers, and web developers to collaboratively design the database. This paper outlines the main features of IsoBank and provides a focused description of the core metadata structure. We present plans for future database and tool development and engagement across the scientific community. These efforts will help facilitate interdisciplinary collaboration among the many users of stable isotopic data while also offering useful data resources and standardization of metadata reporting across eco-geoinformatics landscapes.

Effective management and conservation of threatened species biodiversity requires knowledge of reproductive biology, such as cyclicity, mode, and age at maturity. We combined reproductive endocrinology and in-situ ultrasonography to examine reproductive characteristics of female Caribbean reef sharks Carcharhinus perezi, a widely distributed, threatened marine predator which remains largely understudied throughout its range. Unique to this study was the opportunity to conduct longitudinal assessments of two individuals, recaptured across multiple seasons during sampling in The Bahamas. Within-individual, paired hormone analyses and in-situ ultrasounds of female sharks that were confirmed as either pregnant, non-pregnant, or reproductively active, suggest a biennial reproductive cycle for Carcharhinus perezi. This unique opportunity to assess the reproductive biology of the same individuals over time underscore the importance of repeated sampling for elucidating population reproductive cyclicity of highly mobile sharks in the wild.

Abstract Income and capital breeding represent opposing ends of a continuum of reproductive strategies. Quantifying nutrient allocation to reproduction is challenging, but recent advances in compound‐specific stable isotope analysis hold promise for tracing the source of individual compounds allocated to reproduction. Here, we describe a novel approach of using measured carbon (δ13C) and nitrogen (δ15N) isotope values of individual amino acids (AAs) in pectoral muscle of egg‐laying females and egg yolk as a useful tool to quantify the reliance on income versus capital breeding in migrating species. We used white‐fronted (Anser albifrons frontalis), lesser snow (A. caerulescens caerulescens) and black brant (Branta bernicla nigricans) geese breeding in tundra ecosystems of northern Alaska as model organisms. All three species relied on mixed capital–income breeding strategies, but models based on AA isotope data estimated higher proportional contributions of endogenous resources to yolk synthesis compared to results based on bulk tissue isotope analyses. Tracing income versus capital nutrient allocation in migratory species at the compound level is a major advance from the current ‘elemental’ perspective obtained from bulk tissue stable isotope analyses. Our framework is applicable to all taxonomic groups, as long as there is a sufficient spatial or temporal isotopic gradient between resources obtained during the breeding and non‐breeding periods.

Abstract 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.

Misty Groupers (Hyporthodus mystacinus) are one of the largest and most geographically widespread grouper species and one of the few grouper species known to occur at depths greater than 200 m. However, aspects of their basic biology, behavior, and ecology remain poorly understood, leaving significant gaps in our ability to evaluate their functional role throughout the vertical water column, as well as our understanding of their conservation needs in a changing ocean. Through in-situ video observation obtained using deep-sea landers in both The Bahamas and Cayman Islands over multiple years, we documented Misty Grouper occurrence up to 470 m depth in the mesopelagic zone. These observations provide a new depth range extension for the species and illuminate the potential importance of deep-water habitats for large grouper species in the wider Caribbean.

Methane (CH4) hydrate dissociation and CH4 release are potential geohazards currently investigated using X-ray computed tomography (XCT). Image segmentation is an important data processing step for this type of research. However, it is often time consuming, computing resource-intensive, operator-dependent, and tailored for each XCT dataset due to differences in greyscale contrast. In this paper, an investigation is carried out using U-Nets, a class of Convolutional Neural Network, to segment synchrotron XCT images of CH4-bearing sand during hydrate formation, and extract porosity and CH4 gas saturation. Three U-Net deployments previously untried for this task are assessed: (1) a bespoke 3D hierarchical method, (2) a 2D multi-label, multi-axis method and (3) RootPainter, a 2D U-Net application with interactive corrections. U-Nets are trained using small, targeted hand-annotated datasets to reduce operator time. It was found that the segmentation accuracy of all three methods surpass mainstream watershed and thresholding techniques. Accuracy slightly reduces in low-contrast data, which affects volume fraction measurements, but errors are small compared with gravimetric methods. Moreover, U-Net models trained on low-contrast images can be used to segment higher-contrast datasets, without further training. This demonstrates model portability, which can expedite the segmentation of large datasets over short timespans.

This study characterizes the world’s largest seagrass ecosystem in The Bahamas by integrating spatial estimates with remote sensing and performing extensive ground-truthing of benthic habitat with 2,542 diver surveys, as well as data obtained from instrument-equipped tiger sharks, which have strong fidelity to seagrass ecosystems.

The genus Etmopterus is the most speciose group of small bodied deep-sea sharks found throughout the tropical and subtropical Western Atlantic. Despite exhibiting a global distribution at the genus-level, the blurred lantern shark (Etempoterus bigelowi) is known only from a few records in the Western and Southern Atlantic Ocean. Through in-situ video observations using deep-sea landers, we provide two new locality records of the blurred lantern shark from the deep waters off the Cayman Islands, Caribbean Sea. Three unique individuals were recorded across two separate deployments between 653m – 668m. These observations provide the first records of this species in the Caribbean Sea, adding to the minimal knowledge of the species’ distribution throughout the Western Atlantic Ocean.

This paper is an overview of various features of regional anesthesia (RA) and aims to introduce spine surgeons unfamiliar with RA. RA is commonly used for procedures that involve the lower extremities, perineum, pelvic girdle, or lower abdomen. However, general anesthesia (GA) is preferred and most commonly used for lumbar spine surgery. Spinal anesthesia (SA) and epidural anesthesia (EA) are the most commonly used RA methods, and a combined method of SA and EA (CSE). Compared to GA, RA offers numerous benefits including reduced intraoperative blood loss, arterial and venous thrombosis, pulmonary embolism, perioperative cardiac ischemic incidents, renal failure, hypoxic episodes in the postanesthetic care unit, postoperative morbidity and mortality, and decreased incidence of cognitive dysfunction. In spine surgery, RA is associated with lower pain scores, postoperative nausea and vomiting, positioning injuries, shorter anesthesia time, and higher patient satisfaction. Currently, RA is mostly used in short lumbar spine surgeries. However, recent findings illustrate the possibility of applying RA in spinal tumors and spinal fusion. Various researches reveal that SA is an effective alternative to GA with lower minor complications incidence. Comprehensive insight on RA will promote spine surgery under RA, thereby broadening the horizon of spine surgery under RA.

Category: Hindfoot; Basic Sciences/Biologics; Other Introduction/Purpose: Minimally Invasive (MIS) calcaneal osteotomy has grown in popularity in recent years to address hindfoot deformity. A potential complication is thermal bone necrosis secondary to heat generation from the burr, leading to nonunion of the osteotomy. Irrigation is commonly employed to reduce this risk. The effect of irrigation on reducing this risk remains an understudied area. The purpose of this study was to evaluate the effect of cooled versus room-temperature irrigation on thermal energy dissipation on a temperature curve during calcaneal osteotomy using a Shannon burr. Methods: Ten cadaveric limbs (5 pairs) at room temperature (68 0F) were randomized to receive either cooled saline or room temperature irrigation during MIS calcaneal osteotomy. Two thermocouple probes (EL-USB-TC-LCD, Lascar Electronics) were inserted 5mm away from the plane of the osteotomy, on proximal and distal sides respectively (Fig. 1). The probes were inserted to a depth of 2cm. A 3 x 30mm Shannon burr was used to perform the osteotomy. The burr was run continuously under continuous irrigation using either room temperature (680F) and chilled (370F) irrigation, until the osteotomy was completed. All osteotomies were performed in approximately 60 seconds. Temperature was recorded at 15sec, 30sec, 45 sec and 60 sec for the two groups and used as a measure of thermal energy generation. Results: Both room temperature and chilled irrigation were effective in minimizing temperature change. On the proximal side, an overall mean increase of 2.60F (70.60F) with room temperature irrigation and a mean increase of 0.70F (68.70F) with chilled irrigation were observed at the 60 sec interval (p=0.09). On the distal side both irrigation methods were more effective in heat control (70.20F vs 67.10F; p=0.17). Conclusion: For the duration of a MIS calcaneal osteotomy, both continuous room temperature and chilled irrigation can reduce thermal energy generation. Use of chilled irrigation can be considered for osteotomies of denser bone that may take longer to perform and generate higher temperatures.

Background: Minimally invasive (MIS) calcaneal osteotomy has grown in popularity in recent years to address hindfoot deformity. A potential complication is thermal bone necrosis secondary to heat generation from the burr that may lead to osteotomy nonunion. Irrigation is commonly employed to reduce this risk. The effect of irrigation on reducing heat accumulation remains an understudied area. The purpose of this study was to evaluate the effect of cooled vs room-temperature irrigation on thermal energy dissipation during calcaneal osteotomy using a Shannon burr. Methods: Fourteen cadaveric limbs at room temperature (68 °F) were randomized to receive either cooled saline (7 limbs) or room-temperature (7 limbs) irrigation during MIS calcaneal osteotomy. Two thermocouple probes were inserted 5 mm away from the plane of the osteotomy, on the proximal and distal sides, respectively. A 3 × 30-mm Shannon burr was used to perform the osteotomy. The burr was run continuously with continuous irrigation using either room-temperature (68 °F) or chilled (37 °F) irrigation, until the osteotomy was completed. Temperature was recorded at 0, 15, 30, 45, and 60 seconds for the 2 groups and used as a measure of thermal energy accumulation. Results: Both room-temperature and chilled irrigation were effective in minimizing temperature change. On the proximal side, an overall mean increase of 2.5 °F with room-temperature irrigation and a mean decrease of 1.0 °F with chilled irrigation were observed at the 60-second interval ( P = .004). On the distal side, there was a mean increase of 1.3 °F with room-temperature irrigation and a mean increase of 0.5 °F with chilled irrigation ( P = .05). Conclusion: For the duration of an MIS calcaneal osteotomy, both continuous room-temperature and chilled irrigation can minimize temperature increases and potentially reduce the risk of an osteotomy nonunion. Clinical Relevance: Both room-temperature and chilled irrigation can minimize bone temperature increases during MIS calcaneal osteotomy.

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.

As sample preparation and imaging techniques have expanded and improved to include a variety of options for larger sized and numbers of samples, the bottleneck in volumetric imaging is now data analysis. Annotation and segmentation are both common, yet difficult, data analysis tasks which are required to bring meaning to the volumetric data. The SuRVoS application has been updated and redesigned to provide access to both manual and machine learning-based segmentation and annotation techniques, including support for crowd sourced data. Combining adjacent, similar voxels (supervoxels) provides a mechanism for speeding up segmentation both in the painting of annotation and by training a segmentation model on a small amount of annotation. The support for layers allows multiple datasets to be viewed and annotated together which, for example, enables the use of correlative data (e.g. crowd-sourced annotations or secondary imaging techniques) to guide segmentation. The ability to work with larger data on high-performance servers with GPUs has been added through a client-server architecture and the Pytorch-based image processing and segmentation server is flexible and extensible, and allows the implementation of deep learning-based segmentation modules. The client side has been built around Napari allowing integration of SuRVoS into an ecosystem for open-source image analysis while the server side has been built with cloud computing and extensibility through plugins in mind. Together these improvements to SuRVoS provide a platform for accelerating the annotation and segmentation of volumetric and correlative imaging data across modalities and scales.

Abstract 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.

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.

The Caribbean reef shark (Carcharhinus perezi; Poey, 1876) is a medium to large-bodied coastal and reef-associated predator found throughout the subtropical and tropical waters of the Atlantic Ocean and Caribbean Sea, although its populations are increasingly threatened by overfishing. We describe the first mitochondrial genome sequence for this species, using Illumina MiSeq sequencing of an individual from The Bahamas. We report the mitogenome sequence of the Caribbean reef shark to be 16,709 bp and composed two rRNA genes, 22 tRNA genes, 13 protein-coding genes, 2 non-coding regions; the D-loop control region and the origin of light-strand replication. We discuss the implications of this new information on future monitoring efforts and conservation measures such as marine protected areas, and urge for greater application of mitochondrial studies of sharks in the Atlantic Ocean.

Abstract 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.

In this paper, a flexible numerical framework to provide thermal performance assessment for the underground buried cables, considering different geological and meteorological conditions, has been presented. Underground cables tend to retain the heat produced in the conductor, so complex coupled thermo-hydraulic response of the porous medium surrounding the cables needs to be assessed to prevent cable overheating and the associated reduction in cable capacity for carrying current. Applying a coupled thermo-hydraulic model within the developed numerical framework to conduct a health assessment on a subset of National Grid Electricity Transmission’s underground cables, this study provides novel insights into the thermal behaviour of buried circuits. The results indicate that backfill and surrounding native soil have the dominant effect on the thermal behaviour of cables, while the amount of precipitation and ambient temperature were found to have less impact on cable’s thermal behaviour. The findings strongly infer that the nature of the overloading which is undertaken in practice would have no ongoing negative impact, suggesting that more frequent or longer duration overloading regimes could be tolerated. Overall, this study demonstrates how the developed numerical framework could be harnessed to allow safe rating adjustments of buried transmission circuits.

Background: With the development of the COVID-19 pandemic, elective foot and ankle surgeries were delayed throughout the United States to divert health care resources and limit exposure. Little is known about the impact of COVID-19 on patient’s willingness to proceed with elective procedures once restrictions are lifted and factors contributing to such decision. Methods: Patients across 6 US orthopedic institutions who had their elective foot and ankle surgeries cancelled secondary to the pandemic were given a questionnaire. Specifically, patients were asked about their willingness to move forward with surgery once restrictions were lifted and if not why. Pain-level and pain medication use were also assessed. Univariate analysis was used to identify factors that contribute to patient’s decisions. Results: A total of 150 patients participated in this study. Twenty-one (14%) opted not to proceed with surgery once restrictions were lifted. Forty-three percent (n = 9) listed concern for COVID infection as the reason; however, 14% of them would proceed if procedures were performed in surgery center. Twenty-nine (19% of the total cohort) patients had increased pain and 11% of patients were taking more pain meds because of the delay to their procedure. Patients who decided not to proceed with surgery reported pain reduction (3% vs 14%) and lower increase in pain medication used (5% vs 12%). Conclusion: COVID-19 has made a significant impact on the health care system. Delay of elective foot and ankle procedures impact patient quality of life and outcomes. Access to surgery centers may provide a partial solution during the pandemic Level of Evidence: Level III.

Blue sharks (Prionace glauca) are globally distributed, large-bodied pelagic sharks that make extensive migrations throughout their range. In the North Pacific, mark-recapture studies have shown trans-Pacific migrations, but knowledge gaps in migration frequency hinder understanding of regional connectivity and assessments of regional demography for stock assessments. Here, we use oceanographic gradients of stable isotope ratios (i.e., regional isoscapes) to determine exchange rates of blue sharks between the East and West North Pacific Ocean (EPO and WPO). We generated regional δ13C and δ15N distributions for blue sharks from published values in the North Pacific (n = 180; both sexes, juveniles and adults combined). Discriminant analysis suggested low trans-Pacific exchange, categorizing all western (100%) and most eastern (95.3%) blue sharks as resident to their sampling region, with isotopic niche overlap of WPO and EPO highly distinct (0.01–5.6% overlap). Limited trans-Pacific movements suggest that other mechanisms maintain genetic mixing of the North Pacific blue shark population. Potential finer scale movement structure was indicated by isotopic differences in sub-regions of the eastern and western Pacific, though application of mixing models are currently limited by aberrantly low blue shark δ13C values across studies. Our results suggest that blue shark population dynamics may be effectively assessed on a regional basis (i.e., WPO and EPO). We recommend further studies to provide size- and sex-specific movement patterns based on empirical isotopic values with large sample sizes from targeted regions. Strategically applied stable isotope approaches can continue to elucidate migration dynamics of mobile marine predators, complementing traditional approaches to fisheries biology and ecology.

Abstract Adolescents (12–17 years of age) with severe eosinophilic asthma experience frequent exacerbations and reduced lung function leading to poor health-related quality of life. Mepolizumab is approved for add-on maintenance therapy in patients with severe eosinophilic asthma ≥ 6 years of age in the EU and ≥ 12 years of age in other regions (including the USA), based on a Phase II/III program demonstrating reduced exacerbation rates with 4-weekly treatment. A total of 34 adolescent patients were recruited across the Phase III mepolizumab trials. Consistent with outcomes in the overall population, there was a reduction in the annual rate of clinically significant exacerbations, along with a reduction in blood eosinophil counts in response to mepolizumab in adolescent patients. The safety profile in adolescent patients was consistent with that seen in the overall population. Data from the Phase III clinical development program provide evidence for comparable efficacy and safety of mepolizumab between adolescents with severe eosinophilic asthma and the overall population. Clinical trial registration DREAM, NCT01000506 [MEA112997]; MENSA, NCT01691521 [MEA115588]; SIRIUS, NCT01691508 [MEA115575]; MUSCA, NCT02281318 [200862]; COSMOS, NCT01842607 [MEA115661].

Abstract The notion that closely related species resemble each other in ecological niche space (i.e., phylogenetic dependence) has been a long‐standing, contentious paradigm in evolutionary biology, the incidence of which is important for predicting the ecosystem‐level effects of species loss. Despite being examined across a multitude of terrestrial taxa, many aspects of niche conservatism have yet to be explored in marine species, especially for characteristics related to resource use and trophic behavior (Eltonian niche characteristics, ENCs). We combined ENCs derived from stable isotope ratios at assemblage‐ and species‐levels with phylogenetic comparative methods, to test the hypotheses that benthic marine fishes (1) exhibit similar assemblage‐wide ENCs regardless of geographic location and (2) display phylogenetically dependent ENCs at the species level. We used a 12‐species sub‐set of the monophyletic group Rajidae sampled from three independent assemblages (Central California, Gulf of Alaska, and Northwest Atlantic), which span two ocean basins. Assemblage‐level ENCs implied low trophic diversity and high evenness, suggesting that Rajidae assemblages may exhibit a well‐defined trophic role, a trend consistent regardless of geographic location. At the species level, we found evidence for phylogenetic dependence of ENCs relating to trophic diversity (i.e., isotopic niche width; SEAc). Whether individuals can be considered functional equivalents across assemblages is hard to ascertain because we did not detect a significant phylogenetic signal for ENCs relating to trophic function (e.g., trophic position). Thus, additional, complimentary approaches are required to further examine the phylogenetic dependence of species functionality. Our approach illustrates the potential of stable isotope‐derived niche characteristics to provide insight on macroecological processes occurring across evolutionary time, which could help predict how assemblages may respond to the effects of species loss.

Marine protected areas (MPAs) have emerged as potentially important conservation tools for the conservation of biodiversity and mitigation of climate impacts. Among MPAs, a large percentage has been created with the implicit goal of protecting shark populations, including 17 shark sanctuaries which fully protect sharks throughout their jurisdiction. The Commonwealth of the Bahamas represents a long-term MPA for sharks, following the banning of commercial longlining in 1993 and subsequent designation as a shark sanctuary in 2011. Little is known, however, about the long-term behavior and space use of sharks within this protected area, particularly among reef-associated sharks for which the sanctuary presumably offers the most benefit. We used acoustic telemetry to advance our understanding of the ecology of such sharks, namely Caribbean reef sharks (Carcharhinus perezi) and tiger sharks (Galeocerdo cuvier), over two discrete islands (New Providence and Great Exuma) varying in human activity level, over 2 years. We evaluated which factors influenced the likelihood of detection of individuals, analyzed patterns of movement and occurrence, and identified variability in habitat selection among species and regions, using a dataset of 23 Caribbean reef sharks and 15 tiger sharks which were passively monitored in two arrays with a combined total of 13 acoustic receivers. Caribbean reef sharks had lower detection probabilities than tiger sharks, and exhibited relatively low habitat connectivity and high residency, while tiger sharks demonstrated wider roaming behavior across much greater space. Tiger sharks were associated with shallow seagrass habitats where available, but frequently transited between and connected different habitat types. Our data support the notion that large MPAs afford greater degrees of protection for highly resident species such as Caribbean reef sharks, yet still may provide substantial benefits for more migratory species such as tiger sharks. We discuss these findings within the context of species-habitat linkages, ecosystem services, and the establishment of future MPAs.

Category: Ankle; Ankle Arthritis; Arthroscopy; Bunion; Hindfoot; Lesser Toes; Midfoot/Forefoot; Sports Introduction/Purpose: With the development of the COVID-19 pandemic, elective foot and ankle surgeries were delayed throughout the U.S. to divert healthcare resources and limit exposure. Little is known about the impact of COVID-19 on patient’s willingness to proceed with elective procedures once restrictions are lifted and factors contributing to such decision. Methods: Patients across six U.S. Orthopedic Institutions who had their elective foot and ankle surgeries cancelled secondary to the pandemic were given a questionnaire. Specifically, patients were asked about their willingness to move forward with surgery once restrictions were lifted and if not why. Pain-level and pain medication use were also assessed. Univariate analysis was used to identify factors that contribute to patient’s decisions. Results: A total of 150 patients participated in this study. N=21 (14%) opted not to proceed with surgery once restrictions were lifted. 43% (N=9) listed concern for COVID infection as the reason, however, 14% of them would proceed if procedures were performed in surgery center. Twenty-nine (19% of the total cohort) patients had increased pain and 11% of patients were taking more pain meds because of the delay to their procedure. Patients who decided not to proceed with surgery reported pain reduction (3% vs. 14%) and lower increase in pain medication used (5% vs. 12%). Conclusion: COVID-19 has made a significant impact on the healthcare. Delay of elective foot and ankle procedures impact patient quality of life and outcomes. Access to surgery centers may provide a partial solution during the pandemic.

Category: Ankle Introduction/Purpose: Highly crosslinked polyethylene (HXLPE) was developed for its superior wear properties in comparison to conventional polyethylene (CPE). The higher dose irradiation required for HXLPE may also cause embrittlement, which reduces fatigue resistance and leads to surface cracking or fracture of the polyethylene bearing. Concern over fatigue resistance has prevented widespread adoption of HXLPE for use in in total ankle arthroplasty (TAA). The aim of this study was to determine whether HXLPE has sufficient fatigue strength for total ankle arthroplasty under simulated physiologically relevant motion profiles and loading in the ankle. Methods: A bicondylar, semi-constrained HXLPE TAA design was subjected to 10 million cycles (Mc) of fatigue testing under loading conditions representative of a walking gait. Kinetics and kinematics of gait were incorporated into a computational model (Dassault Systemes / SIMULIA, Johnston, RI), for prediction of peak stresses on the HXLPE insert. Based on predicted peak stresses, worst case component size and loading configuration were identified. Ten samples were tested on a closed loop servohydraulic test frame (MTS Systems Corp., Minneapolis, MN) for 10Mc. Testing was conducted to a peak load of 5600 N (1259lbs), representing approximately 5 times body weight for a 240 lb individual. Following testing, all samples were evaluated for evidence of polyethylene fracture or surface cracking. Results: Peak stresses in the HXLPE insert occurred during heel off, closely corresponding to both peak axial force and dorsiflexion during gait. The smallest sized component had the highest polyethylene insert stresses, whereas larger sized components had more material to bear the same load, resulting in up to a 30% decrease in stress. All 10 specimens completed 10Mc of testing at 5 times body weight without fracture or surface cracking of the polyethylene insert. Conclusion: HXLPE has sufficient fatigue strength to withstand 10Mc of loading at 5 times body weight at the point of peak stresses during gait in total ankle arthroplasty, and therefore, may be mechanically strong enough to withstand the demands of the ankle. Further clinical evidence is necessary to determine if these results translate to adequate fatigue strength with clinical use of HXLPE.

JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—viain vitroselection from a vast library of cyclic peptides—that show selectivity over other KDMs.

Mechanical loading and inflammation interact to cause degenerative disc disease and low back pain (LBP). However, the underlying mechanosensing and mechanotransductive pathways are poorly understood. This results in untargeted pharmacological treatments that do not take the mechanical aspect of LBP into account. We investigated the role of the mechanosensitive ion channel TRPV4 in stretch-induced inflammation in human annulus fibrosus (AF) cells. The cells were cyclically stretched to 20% hyperphysiological strain. TRPV4 was either inhibited with the selective TRPV4 antagonist GSK2193874 or knocked out (KO) via CRISPR-Cas9 gene editing. The gene expression, inflammatory mediator release and MAPK pathway activation were analyzed. Hyperphysiological cyclic stretching significantly increased the IL6, IL8, and COX2 mRNA, PGE2 release, and activated p38 MAPK. The TRPV4 pharmacological inhibition significantly attenuated these effects. TRPV4 KO further prevented the stretch-induced upregulation of IL8 mRNA and reduced IL6 and IL8 release, thus supporting the inhibition data. We provide novel evidence that TRPV4 transduces hyperphysiological mechanical signals into inflammatory responses in human AF cells, possibly via p38. Additionally, we show for the first time the successful gene editing of human AF cells via CRISPR-Cas9. The pharmacological inhibition or CRISPR-based targeting of TRPV4 may constitute a potential therapeutic strategy to tackle discogenic LBP in patients with AF injury.

The purpose of this experimental clinical study was to assess the effects of dark adaptation and acute changes in glycemia on retinal vessel diameters in men. The study included 14 patients (mean age 63 years, range 48–74 years) with type 2 diabetes mellitus and minimal or no diabetic retinopathy. Retinal vessel diameters were assessed using infrared photography before and after dark adaptation, first while fasting and then at peak hyperglycemia during an oral glucose tolerance test (OGTT). Dark adaptation was accompanied by retinal vasodilatation, both during fasting (mean glycemia 7.6 ± 1.7 mM) and postprandial hyperglycemia (15.7 ± 4.2 mM). When fasting, the increase in vein diameter during dark adaptation was 2.0% after 20 min (P=0.018) and 2.9% after 40 min (P=0.010). When subjects were hyperglycemic, the increase during dark adaptation was 2.8% for retinal vein diameters (P=0.027) and 2.0% for retinal artery diameters after 20 min (P=0.002) and 1.7% for retinal artery diameters after 40 min (P=0.022). For identical conditions of light/dark adaptation, retinal vessels were dilated when subjects were fasting compared to postprandial hyperglycemia. Thus, darkness and fasting were both associated with retinal vasodilation in this short-term experiment in patients with type 2 diabetes. Future studies should determine whether both the stimuli of vasodilation lead to retinal hyperperfusion, which would support that they may be involved in the aggravation of diabetic retinopathy.

Despite the ecological and economic importance of the Caribbean reef shark (Carcharhinus perezi), little data exist regarding the movements and habitat use of this predator across its range. We deployed 11 pop-up satellite archival tags on Caribbean reef sharks captured in the northeast Exuma Sound, The Bahamas, to assess their horizontal and vertical movements throughout the water column. Sharks showed high site fidelity to The Bahamas suggesting Bahamian subpopulations remain protected within the Bahamian Shark Sanctuary. Depth data indicate that Caribbean reef sharks spent a significant proportion (72–91%) of their time above 50 m in narrow vertical depth bands, which varied considerably on an individual basis. This may be indicative of high site fidelity to specific bathymetric features. Animals exhibited three broadly categorized sporadic off-bank excursions (more than 50 m excursions) down to a depth of 436.1 m, which were more frequent during the night. These deeper excursions during night may be indicative of foraging in relation to prey on mesophotic reefs, as well as diel-vertically migrating prey from the deeper meso- and bathypelagic zones. These vertical movements suggest that Caribbean reef sharks can be significant vectors of ecosystem connectivity further warranting holistic multi-system management and conservation approaches.

Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 µM), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 µM AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.

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.

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. N(ε)-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. N(ε)-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.

Principles: Intramedullary spinal cord tumours are rare. The long-term results depend on their varying natural histories and the surgical approach. Less extensive tumour resection avoids greater postoperative neurological impairment without a negative impact on postoperative outcome. Methods: Twenty-seven patients who underwent a total of 34 surgical interventions (including 7 reoperations) were clinically and radiologically reinvestigated. Histology revealed 19 glial, 4 nonglial and 4 miscellaneous tumours. Results: Postoperative long-term clinical follow-up (mean 62 months postoperatively) in 25 patients revealed functional improvement in 2 cases, stable conditions in 17 and deterioration in 6. Although there was residual tumour on MRI in 19 of the 22 patients reexamined, stable radiological studies were seen in 15 cases. Despite the high percentage of partial resections or biopsies, good long-term clinical results were found in 19 patients (70%). Conclusion: The long-term outcome depends on tumour biology and the type of surgery. For low-grade astrocytomas we propose partial resection without incurring the risk of major postoperative neurological deficits, with semi-annual and, after 5 years, annual follow-up. Despite the fact that ependymomas are amenable to complete surgical resection, this was achieved in only one of six cases in this series. Postoperative MRI follow-up of intramedullary tumours must be protracted, as most of these tumours are slow-growing. An increase in the extent and intensity of contrast enhancement of the tumours was defined as tumour recurrence or progressive tumour growth.

As concerns about anthropogenic and natural disturbance grow, understanding animal resource use patterns has been increasingly prioritized to predict how changes in environmental conditions, food web structure, and population dynamics will affect biological resilience. Among the tools used to assess resource use, stable isotope analysis has proliferated in ecological studies, particularly in relation to describing intra- and interspecific variation in trophic interactions. Despite a growing need to disseminate scientific information, the inherent limitations of stable isotope ratios and inappropriate synonymizing of distinct evolutionary and ecological processes may mislead ecological inferences in natural systems. This situation necessitates a re-evaluation of the utility of stable isotope ratios to address certain ecological questions. Here, we assess the efficacy of stable isotope ratios to describe two fundamental ecological processes, niche partitioning and individual specialization. Investigation of these processes has increased substantially in accordance with increased access to stable isotope data. This article discusses the circumstances and approaches that are necessary to evaluate niche partitioning and individual specialization, and outlines key considerations for the associated application of stable isotope ratios.

The notion that closely related species resemble each other in ecological niche space (i.e., phylogenetic dependence) has been a long-standing, contentious paradigm in evolutionary biology, the incidence of which is important for predicting the ecosystem-level effects of species loss. Despite being examined across a multitude of terrestrial taxa, many aspects of niche conservatism have yet to be explored in marine species, especially for characteristics related to resource use and trophic behavior (Eltonian niche characteristics, ENCs). We combined ENCs derived from stable isotope ratios at assemblage- and species-levels with phylogenetic comparative methods, to test the hypotheses that benthic marine fishes (1) exhibit similar assemblage-wide ENCs regardless of geographic location and (2) display phylogenetically dependent ENCs at the species level. We used a 12-species sub-set of the monophyletic group Rajidae sampled from three independent assemblages (Central California, Gulf of Alaska, and Northwest Atlantic), which span two ocean basins. Assemblage-level ENCs implied low trophic diversity and high evenness, suggesting that Rajidae assemblages may exhibit a well-defined trophic role, a trend consistent regardless of geographic location. At the species level, we found evidence for phylogenetic dependence of ENCs relating to trophic diversity (i.e., isotopic niche width; SEAc). Whether individuals can be considered functional equivalents across assemblages is hard to ascertain because we did not detect a significant phylogenetic signal for ENCs relating to trophic function (e.g., trophic position). Thus, additional, complimentary approaches are required to further examine the phylogenetic dependence of species functionality. Our approach illustrates the potential of stable isotope-derived niche characteristics to provide insight on macroecological processes occurring across evolutionary time, which could help predict how assemblages may respond to the effects of species loss.