Search

Abstract Introduction Chimeric antigen receptor T‐cell (CAR‐T) therapy is highly effective in B‐cell blood cancers, but there is limited data on its safety and efficacy in intra‐cardiac lymphoma, due to the potential risks of cardiotoxicity and pseudo‐progression. Discussion We discuss four high‐risk cases that were managed with a multi‐disciplinary approach, including baseline cardiac risk assessment and surveillance with multimodal cardiac imaging and serum cardiac biomarkers, elective supportive care in the intensive care unit, and early treatment of cytokine release syndrome. Conclusion CAR‐T therapy can be effective and safe in the treatment of B‐cell blood cancers with intra‐cardiac disease.

A complete accounting of nearby objects—from the highest-mass white dwarf progenitors down to low-mass brown dwarfs—is now possible, thanks to an almost complete set of trigonometric parallax determinations from Gaia, ground-based surveys, and Spitzer follow-up. We create a census of objects within a Sun-centered sphere of 20 pc radius and check published literature to decompose each binary or higher-order system into its separate components. The result is a volume-limited census of ∼3600 individual star formation products useful in measuring the initial mass function across the stellar (

Abstract Severe COVID‐19 disease is a hyperinflammatory, pro‐thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo‐inflammatory markers. Seven critically ill adults with severe COVID‐19 respiratory failure (PaO2:FiO2 ratio 800 IU/L and D‐dimer >1000 μg/L (or doubling from baseline) received PEX, daily, for a minimum of 5 days. No other immunomodulatory medications were initiated during this period. Seven patients matched for age and baseline biochemistry were a comparator group. Coagulation screening revealed no evidence of coagulopathy. However, von Willebrand Factor (VWF) activity, antigen and VWF antigen: ADAMTS13 ratio, Factor VIII and D‐dimers were all elevated. Following 5 days of PEX, plasma levels of all the above, and ferritin levels, were significantly reduced (P

Geranylgeraniol (GG), an ingredient extracted from the South American annatto plant, has been shown to benefit bone and muscle health, is crucial in the biosynthesis of menaquinone-4 and coenzyme Q10, and has pain and inflammation reduction activities. However, no known studies to date have demonstrated the safety and impact of GG supplementation in humans. This 8-week, randomized, placebo-controlled, dose-escalated trial was conducted to determine the effect of GG on blood safety and hormone markers in healthy adults. Sixty-six males and females between 30 and 49 years of age were supplemented with either GG or a placebo (PLA) for 8 weeks, with dose escalation from 150 mg to 300 mg occurring after 4 weeks in the treatment group. Changes in complete blood count and comprehensive metabolic panels were analyzed for whole study groups (males and females) while changes in sex hormone panels were analyzed for males and females independently. There were no significant changes in complete blood count, comprehensive metabolic panel, progesterone, estradiol, sex–hormone binding globulin, or dihydrotestosterone (p > 0.05). An exploratory analysis of testosterone levels in a subgroup of males with baseline (Pre) total testosterone < 700 ng/dL (GG = 15; PLA = 13) demonstrated a significant increase (p < 0.05) from Pre to Week 8 in total-, free-, and bioavailable testosterone (+7.5%, +15.0%, and +14.8%, respectively). This study demonstrates that GG does not significantly change the composition of blood chemistry, hematology, or sex hormone profiles in adult males or females. Given the effects observed in the exploratory analysis in a subgroup of males, GG supplementation may be beneficial for testosterone enhancement in male populations subject to low testosterone (i.e., aging males and those with late-onset hypogonadism), but further research is needed.

IntroductionDry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED.MethodsParticipants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer’s test) and ocular symptoms (Ocular Surface Disease Index [OSDI]).ResultsThe study met its primary endpoints: the LCD group demonstrated significantly better Schirmer’s test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p

Abstract Marine fauna, including coral reefs, exist under particular oceanographic and meteorological (metocean) processes that maintain water quality within the range limits to which they have adapted over millennia. Climate‐induced changes to these metocean processes could alter ambient marine water quality to ranges beyond those limits and at rates faster than species can adapt. Extreme (or marginal) coral reefs, such as those in arid tropical regions, already exist at the limits of their ranges for water quality parameters such as temperature and turbidity. Here, we apply projected anomalies from ensemble climate models to the metocean processes that drive turbidity in the Exmouth Gulf region of north Western Australia where habitats of significant environmental value exist. We also apply projected sea surface temperature anomalies to look at how a combined effect of turbidity and temperature might impact important habitats. We find that turbidity is predicted to increase in some parts of the Gulf and decrease in others due to differing metocean drivers of turbidity throughout the region. Temperature anomalies reveal year‐round increases in temperature consistent with current summer marine heat wave events (>2.5°C above mean temperatures). Climate models used in the predictions varied between themselves underscoring the importance of model choice and of using ensembles.

Abstract Sarcopenia is an increasingly recognized complication of cirrhosis that is associated with morbidity and mortality. Differences in the prevalence and prognosis of sarcopenia between men and women have been reported in other patient groups, but there is insufficient understanding of how sex impacts the prognostic value of sarcopenia in cirrhosis. A search of MEDLINE and Embase was conducted from earliest entries to April 2021. Studies were included if they examined sex‐stratified mortality impact of reduced muscle function or mass in outpatient populations with cirrhosis. We identified 700 studies of which 6 were deemed relevant for inclusion in this narrative review. Studies of interest were heterogeneous, precluding pooling of data and making interpretation of the literature challenging. Muscle mass was assessed in five studies (n = 2566, 1730 men, 836 women) and was reduced in 36–50% of men and 24–43% of women. All five studies found that reduced muscle mass determined by computed tomography, dual‐energy X‐ray absorptiometry, and bioelectrical impedance analysis was associated with increased mortality in men. Of these, two studies identified a corresponding relationship in women; reduced muscle mass defined by computed tomography was associated with increased mortality [hazard ratio (HR) 2.82, P = 0.001], while increasing muscle mass by bioelectrical impedance analysis likewise conferred a survival benefit (HR 0.45, P = 0.0016). Only one study assessed the relationship of muscle function with sex‐stratified mortality (n = 1405, 827 men, 578 women), concluding that reduced muscle function predicted mortality in both men and women (HR 1.65, P

BackgroundRehabilitation is the key to management of patients with subacromial impingement syndrome to prevent disability and loss of function. While point-of-care musculoskeletal ultrasound aids clinical diagnosis of subacromial impingement syndrome, many patients do not demonstrate the classic findings of dynamic supraspinatus tendon impingement beneath the acromion on ultrasound. The objective of this study was to establish the most reliable shoulder ultrasound measurements for subacromial impingement, by evaluating the intra-rater and inter-rater reliability of measurements in asymptomatic participants.MethodsEighteen participants (9 women, 9 men, mean ± standard deviation: 34.6 ± 7.9 years of age) underwent bilateral shoulder ultrasound evaluations with measurements for subacromial impingement (acromiohumeral distance, acromion-greater tuberosity distance, supraspinatus tendon, subacromial-subdeltoid bursa, and subacromial-subdeltoid bursal fluid thickness) performed by two sports medicine physicians. Intra-class coefficients were calculated to determine the intra- and inter-rater reliability of shoulder ultrasound images and measurements.ResultsIntra-rater reliability for acromiohumeral distance (0.76–0.79), supraspinatus tendon (0.91–0.95), subacromial-subdeltoid bursa (0.76–0.84), and subacromial-subdeltoid bursal fluid thickness (0.75–0.81) was found to be good to excellent, whereas inter-rater reliability ranged from poor to moderate.ConclusionsAcromiohumeral distance in neutral position and short axis ultrasound measurements of supraspinatus tendon, subacromial-subdeltoid bursa, and subacromial-subdeltoid bursal fluid thickness in the modified Crass position were the most reliable for subacromial impingement in asymptomatic participants. We recommend validation of these measurements in a symptomatic population to aid diagnosis and direct rehabilitation of patients with suspected subacromial impingement, and to increase point-of-care ultrasound uptake, availability, and training among rehabilitation professionals across health systems.

Seagrass meadows are prominent in many coastal zones worldwide and significant contributors to global primary production. The large bottom roughness (or canopy) created by seagrass meadows substantially alters near-bed hydrodynamics and sediment transport. In this study, we investigate how a seagrass meadow in a low-energy environment (forced by local winds) modifies near-bed mean and wave-driven flows and assess how this relates to suspended sediment concentration (SSC). A two-week field study was conducted at Garden Island in southwestern Australia, a shallow and sheltered coastal region subjected to large diurnal sea-breeze cycles, typical of many low-energy environments where seagrasses are found. The mean and turbulent flow structure, along with optical estimates of SSC, were measured within both a seagrass canopy and over an adjacent bare bed. Near-bed mean current velocities within the seagrass canopy were on average 35% of the velocity above the canopy. Oscillatory wave velocities were less attenuated than mean current velocities, with near-bed values on average being 83% of those above the canopy. Mean and maximum shear velocities inferred from currents and waves above the canopy frequently exceeded the threshold for sediment resuspension, but no significant variation was observed in the SSC. However, a significant correlation was observed between SSC and bed shear stress estimated using near-bed velocities inside the canopy. When sediment was resuspended, there were substantial differences between the SSCs within and above the canopy layer, with higher levels confined within the canopy. This study demonstrates the importance of measuring near-bed hydrodynamic processes directly within seagrass canopies for predicting the role seagrass meadows play in regulating local rates of sediment resuspension.

Tropical coral reef-lined coasts are exposed to storm wave-driven flooding. In the future, flood events during storms are expected to occur more frequently and to be more severe due to sea-level rise, changes in wind and weather patterns, and the deterioration of coral reefs. Hence, disaster managers and coastal planners are in urgent need of decision-support tools. In the short-term, these tools can be applied in Early Warning Systems (EWS) that can help to prepare for and respond to impending storm-driven flood events. In the long-term, future scenarios of flooding events enable coastal communities and managers to plan and implement adequate risk-reduction strategies. Modeling tools that are used in currently available coastal flood EWS and future scenarios have been developed for open-coast sandy shorelines, which have only limited applicability for coral reef-lined shorelines. The tools need to be able to predict local sea levels, offshore waves, as well as their nearshore transformation over the reefs, and translate this information to onshore flood levels. In addition, future scenarios require long-term projections of coral reef growth, reef composition, and shoreline change. To address these challenges, we have formed the UFORiC (Understanding Flooding of Reef-lined Coasts) working group that outlines its perspectives on data and model requirements to develop EWS for storms and scenarios specific to coral reef-lined coastlines. It reviews the state-of-the-art methods that can currently be incorporated in such systems and provides an outlook on future improvements as new data sources and enhanced methods become available.

Coral bleaching driven by ocean warming is one of the most visible ecological impacts of climate change and perhaps the greatest threat to the persistence of reefs in the coming decades. In the absence of returning atmospheric greenhouse gas concentrations to those compatible with ocean temperatures below the mass coral bleaching temperature thresholds, the most straightforward means to reduce thermal-stress induced bleaching is to cool water at the seabed. The feasibility of reducing the seabed temperature through cool-water injections is considered first by analysing the feasibility of doing so on 19 reefs with differing physical environments using a simple residence time metric in 200 m resolution hydrodynamic model configurations. We then concentrate on the reefs around Lizard Island, the most promising candidate of the 19 locations, and develop a 40 m hydrodynamic model to investigate the effect of the injection of cool water at differing volumetric rates. Injecting 27°C seawater at a rate of 5 m3 s-1 at 4 sites in early 2017 cooled 97 ha of the reef by 0.15°C or more. The power required to pump 5 m3 s-1 through a set of pipes over a distance of 3 km from a nearby channel is ∼466 kW. This power applied at 4 sites for 3 months achieves a 2 Degree Heating Weeks (DHWs) reduction on 97 ha of reef. A more precise energy costing will require further expert engineering design of the pumping equipment and energy sources. Even for the most physically favourable reefs, cool-water transported through pipes and injected at a reef site is energy expensive and cannot be scaled up to any meaningful fraction of the 3,100 reefs of the GBR. Should priority be given to reducing thermal stress on one or a few high value reefs, this paper provides a framework to identify the most promising sites.

Understanding the transport and exchange of water masses both within a reef and between a reef and the surrounding ocean is needed to describe a wide-range of ecosystem processes that are shaped by the movement of material and heat. We show how novel Lagrangian data processing methods, specifically developed to reveal key and often hidden transport structures, can help visualize flow transport patterns within and around morphologically complex reef systems. As an example case study, we consider the wave-driven flow transport within the Ningaloo Reef in Western Australia. We show that a network of attracting, repelling, and trapping flow transport structures organizes the flow transport into, around, and out of the reef. This approach is broadly applicable to coral reef systems, since the combination of well-defined bathymetry and persistent flow-forcing mechanisms (e.g., by wave breaking or tides) is conducive to the existence of persistent Lagrangian transport structures that organize material transport.

Canopies formed by aquatic vegetation, such as mangroves, seagrass, and kelp, play a crucial role in altering the local hydrodynamics in rivers, estuaries, and coastal regions, and thereby influence a range of morphodynamic and biophysical processes. Prediction of the influence of canopies on these hydrodynamic processes requires a fundamental understanding of canopy drag, which varies significantly with both flow conditions and canopy properties (such as density and submergence). Although our knowledge on canopy drag has increased significantly in recent decades, a conclusive, physics-based description for canopy drag that can be applied to both emergent and submerged canopies is currently lacking. Here, we extend a new theoretical canopy drag model (that employs the velocity between canopy elements as the reference velocity) to submerged aquatic canopies. The model is validated for the first time with direct measurements of drag forces exerted by canopies across broad ranges of flow conditions and canopy density and submergence. The skill and broader applicability of the model are further assessed using a comprehensive set of existing experimental data, covering a broad range of natural conditions (including flexible vegetation). The resulting model provides a simple tool to estimate canopy drag forces, which govern hydraulic resistance, sediment transport, and biophysical processes within aquatic ecosystems.

Clonality is common in many aquatic plant species, including seagrasses, where populations are maintained through a combination of asexual and sexual reproduction. One common measure used to describe the clonal structure of populations is clonal richness. Clonal richness is strongly dependent on the biological characteristics of the species, and how these interact with the environment but can also reflect evolutionary scale processes especially at the edge of species ranges. However, little is known about the spatial patterns and drivers of clonal richness in tropical seagrasses. This study assessed the spatial patterns of clonal richness in meadows of three tropical seagrass species, Thalassia hemprichii, Halodule uninervis, and Halophila ovalis, spanning a range of life-history strategies and spatial scales (2.5–4,711 km) in Indonesia and NW Australia. We further investigated the drivers of clonal richness using general additive mixed models for two of the species, H. uninervis and H. ovalis, over 8° latitude. No significant patterns were observed in clonal richness with latitude, yet disturbance combined with sea surface temperature strongly predicted spatial patterns of clonal richness. Sites with a high probability of cyclone disturbance had low clonal richness, whereas an intermediate probability of cyclone disturbance and the presence of dugong grazing combined with higher sea surface temperatures resulted in higher levels of clonal richness. We propose potential mechanisms for these patterns related to the recruitment and mortality rates of individuals as well as reproductive effort. Under a changing climate, increased severity of tropical cyclones and the decline in populations of mega-grazers have the potential to reduce clonal richness leading to less genetically diverse populations.