Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study.

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Electromyographic Profile of the Shoulder During Stability Exercises With Kettlebells.

CONTEXT: Shoulder rehabilitation can be a difficult task due to the dynamic nature of the joint complex. Various weight training implements, including kettlebells (KB), have been utilized for therapeutic exercise in the rehabilitation setting to improve shoulder girdle strength and motor control. The KBs are unique in that they provide an unstable load and have been purported to promote greater muscle activation versus standard dumbbells. Recent literature has examined the efficacy of KB exercises for global strengthening and aerobic capacity; however, electromyographic data for shoulder-specific activities are lacking. OBJECTIVE: To examine muscle activation patterns about the rotator cuff and scapular musculature during 5 commonly-utilized KB exercises. DESIGN: Cross-sectional analysis of a single group. SETTING: Clinical biomechanics laboratory. PARTICIPANTS: Ten participants performed all exercises in a randomized order. MAIN OUTCOME MEASURES: Mean electromyographic values for each subject were compared between exercises for each target muscle. RESULTS: Significant differences (P < .05) between exercises were observed for all target muscles except for the infraspinatus. CONCLUSIONS: The data in this study indicates that certain KB exercises may elicit activation of the shoulder girdle at different capacities. Physical therapy practitioners, athletic trainers, and other clinical professionals who intend to optimize localized strengthening responses may elect to prescribe certain exercises over others due to the inherent difference in muscular utilization. Ultimately, this data may serve to guide or prioritize exercise selection to achieve higher levels of efficacy for shoulder strength and stability gains.

Drought reduces floral resources for pollinators.

Climate change is predicted to result in increased occurrence and intensity of drought in many regions worldwide. By increasing plant physiological stress, drought is likely to affect the floral resources (flowers, nectar and pollen) that are available to pollinators. However, little is known about impacts of drought at the community level, nor whether plant community functional composition influences these impacts. To address these knowledge gaps, we investigated the impacts of drought on floral resources in calcareous grassland. Drought was simulated using rain shelters and the impacts were explored at multiple scales and on four different experimental plant communities varying in functional trait composition. First, we investigated the effects of drought on nectar production of three common wildflower species (Lathyrus pratensis, Onobrychis viciifolia and Prunella vulgaris). In the drought treatment, L. pratensis and P. vulgaris had a lower proportion of flowers containing nectar and O. viciifolia had fewer flowers per raceme. Second, we measured the effects of drought on the diversity and abundance of floral resources across plant communities. Drought reduced the abundance of floral units for all plant communities, irrespective of functional composition, and reduced floral species richness for two of the communities. Functional diversity did not confer greater resistance to drought in terms of maintaining floral resources, probably because the effects of drought were ubiquitous across component plant communities. The findings indicate that drought has a substantial impact on the availability of floral resources in calcareous grassland, which will have consequences for pollinator behaviour and populations.

Can Beach Cleans Do More Than Clean-Up Litter? Comparing Beach Cleans to Other Coastal Activities.

Coastal visits not only provide psychological benefits but can also contribute to the accumulation of rubbish. Volunteer beach cleans help address this issue, but may only have limited, local impact. Consequently, it is important to study any broader benefits associated with beach cleans. This article examines the well-being and educational value of beach cleans, as well as their impacts on individuals' behavioral intentions. We conducted an experimental study that allocated students (n = 90) to a beach cleaning, rock pooling, or walking activity. All three coastal activities were associated with positive mood and pro-environmental intentions. Beach cleaning and rock pooling were associated with higher marine awareness. The unique impacts of beach cleaning were that they were rated as most meaningful but linked to lower restorativeness ratings of the environment compared with the other activities. This research highlights the interplay between environment and activities, raising questions for future research on the complexities of person-environment interactions.

Strong effect of dispersal network structure on ecological dynamics.

A central question in ecology with great importance for management, conservation and biological control is how changing connectivity affects the persistence and dynamics of interacting species. Researchers in many disciplines have used large systems of coupled oscillators to model the behaviour of a diverse array of fluctuating systems in nature. In the well-studied regime of weak coupling, synchronization is favoured by increases in coupling strength and large-scale network structures (for example 'small worlds') that produce short cuts and clustering. Here we show that, by contrast, randomizing the structure of dispersal networks in a model of predators and prey tends to favour asynchrony and prolonged transient dynamics, with resulting effects on the amplitudes of population fluctuations. Our results focus on synchronization and dynamics of clusters in models, and on timescales, more appropriate for ecology, namely smaller systems with strong interactions outside the weak-coupling regime, rather than the better-studied cases of large, weakly coupled systems. In these smaller systems, the dynamics of transients and the effects of changes in connectivity can be well understood using a set of methods including numerical reconstructions of phase dynamics, examinations of cluster formation and the consideration of important aspects of cyclic dynamics, such as amplitude.

Lessons to be learnt in managing the breech presentation at term: an 11-year single-centre retrospective study.

BACKGROUND: The 2000 publication of the Term Breech Trial significantly impacted obstetric practice in Australia with a rapid increase in delivery of term breech singletons by caesarean section. More reassuring data from European centres who continued to offer vaginal breech deliveries to carefully selected women have led to a softening of international guidelines which now support an individualised approach to management. The application of this principle to an Australian population, particularly in the wake of such a major change in obstetric practice, has not previously been demonstrated. AIM: To compare short-term neonatal and maternal morbidity for infants with a singleton breech presentation born after 37 weeks, according to planned mode of delivery. MATERIALS AND METHODS: Eleven-year single-centre retrospective study with intention-to-treat analysis based on intended mode of delivery. RESULTS: Two hundred and forty-three of 766 (31.7%) eligible women elected for planned vaginal breech delivery. The overall success rate in this group was 58%. Morbidity rates were low and compare favourably with similar international studies. However, there was a nonsignificant trend towards higher rates of short-term serious neonatal and maternal morbidity in the planned vaginal delivery group (1.6 vs 0.4%, P = 0.08 and 8.2 vs 4.8%, P = 0.06, respectively). CONCLUSIONS: Attempted vaginal delivery for breech presentation remains an option in carefully selected women under strict obstetric protocols.

Retrospective Review of Directional Atherectomy and Drug-Coated Balloon Use in a PAD Safety-Net Population.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality, particularly once patients develop critical limb threatening ischemia (CLTI). Minorities and vulnerable populations often present with CLTI and experience worse outcomes. The use of directional atherectomy (DA) and drug-coated balloon (DCB) during lower-extremity revascularization (LER) has not been previously described in a safety-net population. OBJECTIVE: To review demographic and clinical characteristics, and short- intermediate term outcomes of patients presenting to a safety-net hospital with PAD treated with DA and DCB during LER. METHODS: In this retrospective, observational cohort study, chart review was performed of all patients who underwent DA and DCB during LER for PAD from April 2016 to January 2020 in a safety-net hospital. RESULTS: The analysis included 58 patients, with 41% female, 24% Black/African American, and 31% Hispanic. From this group, 17% spoke a non-English primary language and 10% reported current or previous housing insecurity. Most (65%) presented with CLTI and had undergone a previous index leg LER (58%). The combination of DA and DCB was efficacious, resulting in low rates of bail-out stenting (16%) and target-vessel revascularization (26%) at 2 years. Low complication rates (tibial embolism in 12% and vessel perforation in 2% of cases) were also observed. Most patients (67%) with Rutherford category 5 experienced wound healing by 2 years. CONCLUSION: In this safety-net population, the majority presented with CLTI and a previous LER of the index leg. The combination of DA and DCB resulted in low complication rates, and good short-intermediate outcomes in this frequently undertreated population.

Major declines in NE Atlantic plankton contrast with more stable populations in the rapidly warming North Sea.

Plankton form the base of marine food webs, making them important indicators of ecosystem status. Changes in the abundance of plankton functional groups, or lifeforms, can affect higher trophic levels and can indicate important shifts in ecosystem functioning. Here, we extend this knowledge by combining data from Continuous Plankton Recorder and fixed-point stations to provide the most comprehensive analysis of plankton time-series for the North-East Atlantic and North-West European shelf to date. We analysed 24 phytoplankton and zooplankton datasets from 15 research institutions to map 60-year abundance trends for 8 planktonic lifeforms. Most lifeforms decreased in abundance (e.g. dinoflagellates: -5 %, holoplankton: -7 % decade-1), except for meroplankton, which increased 12 % decade-1, reflecting widespread changes in large-scale and localised processes. K-means clustering of assessment units according to abundance trends revealed largely opposing trend direction between shelf and oceanic regions for most lifeforms, with North Sea areas characterised by increasing coastal abundance, while abundance decreased in North-East Atlantic areas. Individual taxa comprising each phytoplankton lifeform exhibited similar abundance trends, whereas taxa grouped within zooplankton lifeforms were more variable. These regional contrasts are counterintuitive, since the North Sea which has undergone major warming, changes in nutrients, and past fisheries perturbation has changed far less, from phytoplankton to fish larvae, as compared to the more slowly warming North-East Atlantic with lower nutrient supply and fishing pressure. This more remote oceanic region has shown a major and worrying decline in the traditional food web. Although the causal mechanisms remain unclear, declining abundance of key planktonic lifeforms in the North-East Atlantic, including diatoms and copepods, are a cause of major concern for the future of food webs and should provide a red flag to politicians and policymakers about the prioritisation of future management and adaptation measures required to ensure future sustainable use of the marine ecosystem.

Discovery of Novel Inhibitors of Uridine Diphosphate-N-Acetylenolpyruvylglucosamine Reductase (MurB) from Pseudomonas aeruginosa, an Opportunistic Infectious Agent Causing Death in Cystic Fibrosis Patients.

Pseudomonas aeruginosa is of major concern for cystic fibrosis patients where this infection can be fatal. With the emergence of drug-resistant strains, there is an urgent need to develop novel antibiotics against P. aeruginosa. MurB is a promising target for novel antibiotic development as it is involved in the cell wall biosynthesis. MurB has been shown to be essential in P. aeruginosa, and importantly, no MurB homologue exists in eukaryotic cells. A fragment-based drug discovery approach was used to target Pa MurB. This led to the identification of a number of fragments, which were shown to bind to MurB. One fragment, a phenylpyrazole scaffold, was shown by ITC to bind with an affinity of Kd = 2.88 mM (LE 0.23). Using a structure guided approach, different substitutions were synthesized and the initial fragment was optimized to obtain a small molecule with Kd = 3.57 µM (LE 0.35).

A Point-of-Care Algorithm to Guide Proper Device Selection for Ambulatory Electrocardiography.

In the outpatient setting, ambulatory electrocardiography is the most frequently used diagnostic modality for the evaluation of patients in whom cardiac arrhythmias or conduction abnormalities are suspected. Proper selection of the device type and monitoring duration is critical for optimizing diagnostic yield and cost-effective resource utilization. However, despite guidance from major professional societies, the lack of systematic guidance for proper test selection in many institutions results in the need for repeat testing, which leads to not only increased resource utilization and cost of care, but also suboptimal patient care. To address this unmet need at our own institution, we formed a multidisciplinary panel to develop a concise, yet comprehensive algorithm, incorporating the most common indications for ambulatory electrocardiography, to efficiently guide clinicians to the most appropriate test option for a given clinical scenario, with the goal of maximizing diagnostic yield and optimizing resource utilization. The algorithm was designed as a single-page, color-coded flowchart to be utilized both as a rapid reference guide in printed form, and a decision support tool embedded within the electronic medical records system at the point of order entry. We believe that systematic adoption of this algorithm will optimize diagnostic efficiency, resource utilization, and importantly, patient care and satisfaction.

Frequency responses of age-structured populations: Pacific salmon as an example.

Increasing evidence of the effects of changing climate on physical ocean conditions and long-term changes in fish populations adds to the need to understand the effects of stochastic forcing on marine populations. Cohort resonance is of particular interest because it involves selective sensitivity to specific time scales of environmental variability, including that of mean age of reproduction, and, more importantly, very low frequencies (i.e., trends). We present an age-structured model for two Pacific salmon species with environmental variability in survival rate and in individual growth rate, hence spawning age distribution. We use computed frequency response curves and analysis of the linearized dynamics to obtain two main results. First, the frequency response of the population is affected by the life history stage at which variability affects the population; varying growth rate tends to excite periodic resonance in age structure, while varying survival tends to excite low frequency fluctuation with more effect on total population size. Second, decreasing adult survival strengthens the cohort resonance effect at all frequencies, a finding that addresses the question of how fishing and climate change will interact.

Exclusion of a Giant Coronary Artery Aneurysm With Covered Stents Using a Long Drug-Eluting Stent Scaffold.

Coronary artery aneurysms (CAA) are a rare cause of acute coronary syndrome and there is little consensus as to the optimal treatment. Based on case series as well as expert opinion, surgery has been suggested as the optimal treatment for a giant CAA. Here, we present the case of a patient with recurrent myocardial infarction and severe angina due to a giant CAA, who was deemed a poor surgical candidate due to his multiple medical comorbidities. Given his intractable anginal symptoms despite medical therapy, he chose to pursue percutaneous intervention. However, the aneurysm was larger than available covered coronary stents and the patient had significant atherosclerotic disease proximal and distal to the aneurysm itself. Our approach used a long drug-eluting stent as a scaffold to overlap covered coronary stents to successfully exclude the aneurysm. The patient's angina resolved and had no complications or readmissions after nearly 1 year of follow-up.

Small-world properties emerge in highly compartmentalized networks with intermediate group sizes and numbers.

Many recent studies have focused on two statistical properties observed in diverse real-world networks: the small-world property and compartmentalization [D. J. Watts and S. H. Strogatz, Nature 393, 440 (1998); M. Girvan and M. E. J. Newman, Proc. Natl. Acad. Sci. 99, 7821 (2002)]. Models that include group affiliations have been shown to produce networks with high clustering coefficients, a necessary condition for small-world properties [M. E. J. Newman, Phys. Rev. E, 68, 026121 (2003); M. E. J. Newman and J. Park, Phys. Rev. E 68, 036122 (2003)]. However, the consequences of varying the number and size of groups in a network are not well understood. In order to investigate the consequences of group organization, we examined sets of networks that varied simultaneously in the size and number of groups, while maintaining the same overall size and average degree. Here we show that the small-world property arises in maximally compartmentalized and clustered networks that occur in the intermediate region between few, very large groups and many, very small groups.