Abstract Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelial receptor tyrosine kinase Tie2. Signalling by angiopoietin-1 promotes vascular endothelial cell survival and the ...sprouting and reorganisation of blood vessels, as well as inhibiting activation of the vascular endothelial barrier to reduce leakage and leucocyte migration into tissues. Angiopoietin-2 generally has an opposing action, and is released naturally at times of vascular growth and inflammation. There is a significant body of emerging evidence that promoting the actions of angiopoietin-1 through Tie2 is of benefit in pathologies of vascular activation, such as sepsis, stroke, diabetic retinopathy and asthma. Similarly, methods to inhibit the actions of angiopoietin-2 are emerging and have been demonstrated to be of preclinical and clinical benefit in reducing tumour angiogenesis. Here the author reviews the evidence for potential benefits of modulation of the interaction of angiopoietins with Tie2, and the potential applications. Additionally, methods for delivery of the complex protein angiopoietin-1 are discussed, as well as potentially deleterious consequences of administering angiopoietin-1.
Anaerobic digestion (AD) is an economically viable manure treatment option for large dairies (>500 cows) in the U.S. However, roughly 90% of U.S. dairies have less than 200 cows, making this ...technology economically inaccessible to the vast majority of U.S. dairies. While there have been case studies of individual small dairies with anaerobic digesters, there are no comparative studies using cost data from these systems. The objectives of this study were to (1) determine the economic viability of small-scale U.S. digesters using cost data from nine existing 100 to 250-cow dairies and seven theoretical systems and (2) reevaluate the minimum size dairy farm needed for economically feasible AD in the U.S. Cash flow analysis results showed that total capital costs, capital costs per cow, and net costs per cow generally decreased with increasing herd size in existing systems. Among existing revenue streams, use of digested solids for bedding generated the highest revenue ($100cow−1year−1), followed by biogas use for heating and/or electrical generation ($47 to $70cow−1year−1) and CO2 credits ($7cow−1year−1). No system had a positive cash flow under the assumed conditions (8% discount rate, 20-year term). However, six of the 16 systems had positive cash flows when 50% cost sharing was included in the analysis. Our results suggest that, with cost sharing, economically viable AD systems are possible on 250-cow dairies. Additional revenue streams, such as tipping fees for food waste, may reduce the minimum size to 100-cow dairies.
► We performed a cost analysis of the small-scale systems to determine the economic viability of these systems. ► Small-scale systems are often not economically viable without cost-sharing opportunities. ► Bedding reuse is the greatest revenue source available to small-scale systems.
Objective:
To assist healthcare professionals in their management of military personnel and veterans by providing information on the importance of sub-syndromal PTSD.
Conclusion:
Sub-syndromal PTSD ...occurs when persons experience many of the symptoms of PTSD, with some impairment, but do not meet full diagnostic criteria. Found to be associated with a range of mental health conditions including alcohol abuse, higher rates of suicidal ideas and delayed-onset PTSD, it should be seen as ‘symptoms that are predictive of later disorder’. Patients with this condition need accurate assessment, trauma-focused therapy and follow-up to address the symptoms and, potentially, prevent development of PTSD.
Purpose
Lower gastrointestinal (GI) bleeding is defined as bleeding distal to the ligament of Treitz. In the UK, it represents approximately 3 % of all surgical referrals to the hospital. This review ...aims to provide review of the current evidence regarding the management of this condition.
Methods
Literature was searched using Medline, Pubmed, and Cochrane for relevant evidence by two researchers. This was conducted in a manner that enabled a narrative review of the evidence covering the aetiology, clinical assessment and management options of continuously bleeding patients.
Findings
The majority of patients with acute lower GI bleeding can be treated conservatively. In cases where ongoing bleeding occurs, colonoscopy is still the first line of investigation and treatment. Failure of endoscopy and persistent instability warrant angiography, possibly preceded by CT angiography and proceeding to superselective embolisation. Failure of embolisation warrants surgical intervention.
Conclusions
There are still many unanswered questions. In particular, the development of a more reliable predictive tool for mortality, rebleeding and requirement for surgery needs to be the ultimate priority. There are a small number of encouraging developments on combination therapy with regard to angiography, endoscopy and surgery. Additionally, the increasing use of haemostatic agents provides an additional tool for the management of bleeding endoscopically in difficult situations.
This study aimed to test the hypothesis that a novel nutritional blend composed of tryptophan, glycine, magnesium, tart cherry powder, and l -theanine enhances subjective and objective measures of ...sleep during free living conditions.
In a randomized, repeated-measures crossover and double-blind deception design, participants ( n = 9 males and 7 females, age = 24 ± 3 yr, body mass = 69.8 ± 11.6 kg, stature = 170.8 ± 9.1 cm) completed a 3-d familiarization period, followed by 3-d intervention and placebo trials. Subjective Pittsburgh Quality Sleep Index, Core Consensus Sleep Diary, and Karolinska Sleepiness Scale survey tools, alongside objective actigraphy measures of sleep, were assessed, with daily nutritional intake, activity, and light exposure standardized between trials. Participants provided daily urine samples for assessment of targeted and untargeted metabolomes.
The intervention trial reduced sleep onset latency (-24 ± 25 min; P = 0.002), increased total sleep time (22 ± 32 min; P = 0.01), and increased sleep efficiency (2.4% ± 3.9%; P = 0.03), while also reducing morning sleepiness ( P = 0.02). Throughout the study, 75% of participants remained blinded to sleep assessment as a primary outcome measure, with 56% subjectively indicating improved sleep during the intervention trial. Metabolomic analysis highlighted several significantly altered metabolomes related to sleep regulation between trials, inclusive of 6-sulfatoxymelatonin, d -serine, and l -glutamic acid.
Data demonstrate that using the proposed blend of novel nutritional ingredients during free living conditions reduced sleep onset latency, increased total sleep duration, and increased sleep efficiency, leading to reduced perceptions of morning sleepiness. These effects may be mediated by the upregulation of key metabolites involved in the neurophysiological modulation of the sleep/wake cycle.
Atmospheric gravity waves (GWs) play an important role in atmospheric dynamics but accurately representing them in general circulation models (GCMs) is challenging. This is especially true for ...orographic GWs generated by wind flow over small mountainous islands in the Southern Ocean. Currently, these islands lie in the “grey zone” of global model resolution, where they are neither fully resolved nor fully parameterised. It is expected that as GCMs approach the spatial resolution of current high-resolution local-area models, small-island GW sources may be resolved without the need for parameterisations. But how realistic are the resolved GWs in these high-resolution simulations compared to observations? Here, we test a high-resolution (1.5 km horizontal grid, 118 vertical levels) local-area configuration of the Met Office Unified Model over the mountainous island of South Georgia (54∘ S, 36∘ W), running without GW parameterisations. The island's orography is well resolved in the model, and real-time boundary conditions are used for two time periods during July 2013 and June–July 2015. We compare simulated GWs in the model to coincident 3-D satellite observations from the Atmospheric Infrared Sounder (AIRS) on board Aqua. By carefully sampling the model using the AIRS resolution and measurement footprints (denoted as model sampled as AIRS hereafter), we present the first like-for-like comparison of simulated and observed 3-D GW amplitudes, wavelengths and directional GW momentum flux (GWMF) over the island using a 3-D S-transform method. We find that the timing, magnitude and direction of simulated GWMF over South Georgia are in good general agreement with observations, once the AIRS sampling and resolution are applied to the model. Area-averaged zonal GWMF during these 2 months is westward at around 5.3 and 5.6 mPa in AIRS and model sampled as AIRS datasets respectively, but values directly over the island can exceed 50 mPa. However, up to 35 % of the total GWMF in AIRS is actually found upwind of the island compared to only 17 % in the model sampled as AIRS, suggesting that non-orographic GWs observed by AIRS may be underestimated in our model configuration. Meridional GWMF results show a small northward bias (∼20 %) in the model sampled as AIRS that may correspond to a southward wind bias compared to coincident radiosonde measurements. Finally, we present one example of large-amplitude (T′≈15–20 K at 45 km altitude) GWs at short horizontal wavelengths (λH≈30–40 km) directly over the island in AIRS measurements that show excellent agreement with the model sampled as AIRS. This suggests that orographic GWs in the full-resolution model with T′≈45 K and λH≈30–40 km can occur in reality. Our study demonstrates that not only can high-resolution local-area models simulate realistic stratospheric GWs over small mountainous islands but the application of satellite sampling and resolution to these models can also be a highly effective method for their validation.
The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs <30 years old who tested negative for HCV antibody were ...enrolled in a prospective cohort. Risk factors for seroconversion were examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7–32.9/100 person-years). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, P=.11) or a person who was not a sex partner, sharing nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. Interventions to reduce HCV transmission must recognize the importance of relationships on injecting risk
Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) were originally identified as endothelial-specific ligands regulating key functions of the vasculature important in stroke. There ...is increasing evidence that these ligands also exert effects on neurons. Here we review the neuronal effects of VEGF and Ang1 and highlight their potential for therapeutic manipulation in stroke. VEGF stimulates angiogenesis whereas Ang1 suppresses leakage, inflammation and regression of microvessels. Expression of both ligands change dramatically in the brain in experimental stroke, correlating with increased vascular leakage and inflammation. In addition to vascular effects, VEGF can stimulate survival, migration and proliferation of neurons suggesting roles in neural protection and possible therapeutic applications, an idea supported by preclinical studies. Recent reports now demonstrate that Ang1 can also act directly on neurons and enhance neural repair. The realization that VEGF and Ang1 have effects on both neural and vascular compartments impacted by stroke provides new opportunities for therapeutic manipulation to promote neuroprotection and extend the thrombolytic window, as well as stimulating neurogenesis and revascularization.
The circulation of the stratosphere is strongly influenced by the fluxes of gravity waves propagating from tropospheric sources. In the tropics, these gravity waves are primarily generated by ...convection. The Madden‐Julian Oscillation (MJO) dominates the intraseasonal variability of this convection. However, the influence of the MJO on the variability of stratospheric gravity waves is largely unknown. Here we examine gravity wave potential energy at 26 km and the upper tropospheric zonal wind anomaly of the MJO at 200 hPa, sorted by the relative phase of the MJO using the Real Multivariate MJO indices. We show that a strong anticorrelation exists between gravity wave potential energy and the MJO eastward wind anomaly. We propose that this correlation is a result of the filtering of upward propagating waves by the MJO winds. The study provides the first observational evidence that the MJO contributes significantly to the global variability of stratospheric gravity waves in the tropics.
Key Points
MJO signature observed in stratospheric gravity waves
Strong anticorrelation between gravity wave energy and eastward zonal wind anomalies
Evidence that the MJO modulates stratospheric gravity wave activity through wave filtering
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