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A new optimized quasi-helically symmetric configuration is described that has the desirable properties of improved energetic particle confinement, reduced turbulent transport by three-dimensional shaping and non-resonant divertor capabilities. The configuration presented in this paper is explicitly optimized for quasi-helical symmetry, energetic particle confinement, neoclassical confinement and stability near the axis. Post optimization, the configuration was evaluated for its performance with regard to energetic particle transport, ideal magnetohydrodynamic stability at various values of plasma pressure and ion temperature gradient instability induced turbulent transport. The effects of discrete coils on various confinement figures of merit, including energetic particle confinement, are determined by generating single-filament coils for the configuration. Preliminary divertor analysis shows that coils can be created that do not interfere with expansion of the vessel volume near the regions of outgoing heat flux, thus demonstrating the possibility of operating a non-resonant divertor.
OBJECTIVES/GOALS: Non-alcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in the world for which no anti-fibrotic therapies exist. We hypothesized that BMS-22 and maraviroc (MVC), chemokine receptor 2 (CCR2) and 5 (CCR5) antagonists, respectively, would diminish the fibrogenic activity of "fat-exposed" murine pHSCs. METHODS/STUDY POPULATION: pHSCs were isolated from livers of 6 week old male mice following 4 weeks on a NASH-inducing choline-deficient high fat diet (CDAHFD, “fat-exposed”) or standard diet (SD) and passaged in vitro. Early passage (6-12) pHSCs were plate-adhered and TGF-b-treated (10ng/mL) to maximally activate their pro-fibrogenic genes, collagen 1α1 (Col1A1), tissue inhibitor of metalloproteinase 1 (TIMP1), or α-smooth muscle actin (ACTA2). CDAHFD and SD pHSCs were then treated for 48 hours with increasing doses of BMS-22 or MVC (range: 0.3-120ng/mL) to determine (1) the degree of attenuation of the pro-fibrogenic response as measured by qPCR of fibrogenic genes (Col1A1, TIMP1,ACTA2); (2) enhancement of a fibrolytic response as measured by qPCR of matrix metalloproteinases (MMP) 2, 9 and 13 genes; and (3) pHSC migration using the scratch assay. Cell viability and CCR2 and CCR5 gene expression in response to escalating doses of antagonists were also measured. RESULTS/ANTICIPATED RESULTS: Plate- and TGF-b activated CDAHFD pHSCs had a 2-fold greater, dose-dependent attenuation of their pro-fibrogenic activity in response to BMS-CCR2-22 and MVC, when compared with plate- and TGF-b activated SD pHSCs, as measured by reductions in collagen 1α1 (Col1A1) and α-smooth muscle actin (ACTA2) gene expression. TIMP1 gene expression was unaffected by drug treatment for 48 hours. Cell viability was not affected up to doses of 30ng/mL of each drug. pHSCs also demonstrated a dose-dependent increase in CCR2, CCR5 and MMP-9 gene expression in response to surface receptor antagonism. Migration assays comparing CDAHFD and SD pHSCs in response to escalating doses of MVC and BMS-22 are ongoing and expected to demonstrate a significantly decreased migratory capacity of CDAHFD pHSCs than SD pHSCs in response to therapy, reflecting the increased susceptibility of the “fat-exposed” pHSCs to anti-fibrotic therapy than normal pHSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-fibrotic drugs that dampen pro-fibrogenic activities of “fat-exposed” pHSCs are urgently needed. CCR2 and CCR5 antagonists, BMS-22 and MVC, respectively, can selectively dampen the pro-fibrogenic response of fat-exposed pHSCs, and must be considered for future trials in human NASH. CONFLICT OF INTEREST DESCRIPTION: Dr. Jill Smith has a patent licensing agreement with Immune Therapeutics, Inc.
Proper management of glufosinate in glufosinate-resistant crop technologies is needed to mitigate the likelihood of resistance evolution. Antagonism may result from mixtures of glufosinate and other commonly used POST herbicides in soybean and cotton. Two experiments were conducted at the Arkansas Agricultural Research and Extension Center in Fayetteville, AR, in 2015 and 2016 to evaluate mixtures of glufosinate + clethodim and glufosinate + glyphosate on barnyardgrass, broadleaf signalgrass, johnsongrass, and large crabgrass. Furthermore, droplet spectra analyses were conducted to determine if droplet size was associated with identification of herbicide interactions. Antagonism was dependent on the herbicide rates and the weed species. For barnyardgrass and large crabgrass control 4 wk after treatment, glufosinate + glyphosate was antagonistic at all rates evaluated. When large crabgrass was evaluated, some mixtures (e.g., 595 g ha–1 glufosinate + 76 g ha–1 clethodim) had a significant reduction in control relative to one of the herbicides applied alone. Glufosinate (451 and 595 g ai ha–1) + glyphosate (867 and 1,735 g ae ha–1) was antagonistic at all four possible rate combinations for broadleaf signalgrass control. Fewer instances of antagonism were observed for seedling johnsongrass control than for other species, but certain treatments were identified as antagonistic (e.g., glufosinate at 451 g ai ha–1 + clethodim at 76 g ai ha–1). Overall, antagonism was less likely and greater control was observed when the highest rates of both herbicides in a given mixture were used. The addition of glyphosate or clethodim to glufosinate can increase the volume median diameter and decrease the percentage volume of fines, compared to glufosinate alone. The droplet spectra analyses indicate that the glufosinate performance may be negatively affected by the addition of glyphosate or clethodim.
Preclinical and first clinical studies suggested that the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen might be effective in the treatment of alcohol dependence. However, previous randomized controlled trials have reported inconsistent results, possibly related to the low to medium dosages of baclofen used in these studies.
To assess the efficacy and safety of individually titrated high-dose baclofen (30-270 mg/d) for the treatment of alcohol dependence.
Fifty-six alcohol-dependent patients were randomized to a double-blind treatment with individually titrated baclofen or placebo. Multiple primary outcome measures were total abstinence and cumulative abstinence duration during a 12-week high-dose phase.
Preliminary results of this clinical trial will be presented.
Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression.
Aims & objectives
To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial.
We used a randomized, double-blinded, placebo-controlled study design (n = 30; ClinicalTrials.gov, number, NCT00934687).
We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F = 12.30, p = 0.002, η2 = 0.31, d = 1.28).
Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects.
Pedophilia is a disorder where sexual preferences of adults are directed towards children. This disorder impacts society with 1–2 out of every 10 children being sexually approached by an adult, often resulting in prolonged negative psychological effects. Prior research reported structural and functional amygdala alterations in pedophilia. As the neurophenomenological model of sexual arousal suggests the importance of the amygdala in the emotional component, we focused on amygdala functional connectivity in pedophilia.
To investigate amygdala functional connectivity (FC) modulated by expectancy and salient stimuli in pedophilic patients.
Thirteen pedophilic patients and 13 matched healthy controls underwent a salience expectancy task in a 7T ultra high fMRI study. Subjects perceived pictures of naked adults and children. Half of the pictures were preceded by an expectancy cue. Participants were instructed to actively expect the picture depending on the cue. We conducted psychophysiological analysis (PPI) to examine amygdala FC changes in two amygdala sub-regions for child/adult stimuli during the expectancy period and the visual stimuli consummation period using as seed regions the basolateral (BLA) and central nucleus of the amygdala (CeA).
Healthy controls, relative to patients showed significant stronger left CeA to right post-central gyrus FC during expectancy of adult > child picture. For picture condition (adult > child picture) we found significant stronger left CeA to left dorsolateral prefrontal cortex FC in patients compared to healthy controls.
These findings add to the recent literature by indicating that amygdala dysfunctional connectivity is involved in development of deviant sexual behavior.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The introduction of 2,4-D–resistant soybean and cotton provided growers a new POST active ingredient to include in weed management programs. The technology raises concerns regarding potential 2,4-D off-target movement to sensitive vegetation, and spray droplet size is the primary management factor focused on to reduce spray particle drift. The objective of this study was to investigate the droplet size distribution, droplet velocity, and particle drift potential of glyphosate plus 2,4-D choline pre-mixture (Enlist Duo®) applications with two commonly used venturi nozzles in a low-speed wind tunnel. Applications with the TDXL11004 nozzle had larger DV0.1 (291 µm), DV0.5 (544 µm), and DV0.9 (825 µm) values compared with the AIXR11004 nozzle (250, 464, and 709 µm, respectively), and slower average droplet velocity (8.1 m s−1) compared with the AIXR11004 nozzle (9.1 m s−1). Nozzle type had no influence on drift deposition (P = 0.65), drift coverage (P = 0.84), and soybean biomass reduction (P = 0.76). Although the TDXL11004 nozzle had larger spray droplet size, the slower spray droplet velocity could have influenced the nozzle particle drift potential. As a result, both TDXL11004 and AIXR11004 nozzles had similar spray drift potential. Further studies are necessary to understand the impact of droplet velocity on drift potential at field scale and test how different tank solutions, sprayer configurations, and environmental conditions could influence the droplet size and velocity dynamics and consequent drift potential in pesticide applications.
Acifluorfen is a nonsystemic PPO-inhibiting herbicide commonly used for POST Palmer amaranth control in soybean, peanut, and rice across the southern United States. Concerns have been raised regarding herbicide selection pressure and particle drift, increasing the need for application practices that optimize herbicide efficacy while mitigating spray drift. Field research was conducted in 2016, 2017, and 2018 in Mississippi and Nebraska to evaluate the influence of a range of spray droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)], using acifluorfen to create a novel Palmer amaranth management recommendation using pulse width modulation (PWM) technology. A pooled site-year generalized additive model (GAM) analysis suggested that 150-μm (Fine) droplets should be used to obtain the greatest Palmer amaranth control and dry biomass reduction. Nevertheless, GAM models indicated that only 7.2% of the variability observed in Palmer amaranth control was due to differences in spray droplet size. Therefore, location-specific GAM analyses were performed to account for geographical differences to increase the accuracy of prediction models. GAM models suggested that 250-μm (Medium) droplets optimize acifluorfen efficacy on Palmer amaranth in Dundee, MS, and 310-μm (Medium) droplets could sustain 90% of maximum weed control. Specific models for Beaver City, NE, indicated that 150-μm (Fine) droplets provide maximum Palmer amaranth control, and 340-μm (Medium) droplets could maintain 90% of greatest weed control. For Robinsonville, MS, optimal Palmer amaranth control could be obtained with 370-μm (Coarse) droplets, and 90% maximum control could be sustained with 680 μm (Ultra Coarse) droplets. Differences in optimal droplet size across location could be a result of convoluted interactions between droplet size, weather conditions, population density, plant morphology, and soil fertility levels. Future research should adopt a holistic approach to identify and investigate the influence of environmental and application parameters to optimize droplet size recommendations.
Herbicide applications performed with pulse width modulation (PWM) sprayers to deliver specific spray droplet sizes could maintain product efficacy, minimize potential off-target movement, and increase flexibility in field operations. Given the continuous expansion of herbicide-resistant Palmer amaranth populations across the southern and midwestern United States, efficacious and cost-effective means of application are needed to maximize Palmer amaranth control. Experiments were conducted in two locations in Mississippi (2016, 2017, and 2018) and one location in Nebraska (2016 and 2017) for a total of 7 site-years. The objective of this study was to evaluate the influence of a range of spray droplet sizes [150 (Fine) to 900 μm (Ultra Coarse)] on lactofen and acifluorfen efficacy for Palmer amaranth control. The results of this research indicated that spray droplet size did not influence lactofen efficacy on Palmer amaranth. Palmer amaranth control and percent dry-biomass reduction remained consistent with lactofen applied within the aforementioned droplet size range. Therefore, larger spray droplets should be used as part of a drift mitigation approach. In contrast, acifluorfen application with 300-μm (Medium) spray droplets provided the greatest Palmer amaranth control. Although percent biomass reduction was numerically greater with 300-μm (Medium) droplets, results did not differ with respect to spray droplet size, possibly as a result of initial plant injury, causing weight loss, followed by regrowth. Overall, 900-μm (Ultra Coarse) droplets could be used effectively without compromising lactofen efficacy on Palmer amaranth, and 300-μm (Medium) droplets should be used to achieve maximum Palmer amaranth control with acifluorfen.
Chloris spp. are warm-season grasses that outcompete crops for scarce resources throughout Australia. In Queensland, mild winters and increased adoption of conservation tillage practices have led to an increase of this warm-season grass family in winter crops. The objective of this study is to understand whether droplet size (nozzle type) effects herbicide efficacy of summer perennial grasses, as previous research found no effect of droplet size (nozzle type) on herbicide efficacy of winter annual grasses. A study to compare droplet-size (nozzle type) effects on control of windmillgrass and its domesticated relative, rhodesgrass, was conducted at the University of Queensland in Gatton, QLD, Australia. Results showed little difference in dry weight reductions for windmillgrass or rhodesgrass across droplet size (nozzle type). Paraquat applications with the TTI nozzle resulted in significantly lower dry weight reductions compared with other droplet-size sprays (nozzle types) for rhodesgrass. Glyphosate, imazamox plus imazapyr, and clodinafop resulted in commercially acceptable control for both species, regardless of the droplet size (nozzle type) selected, indicating droplet size (nozzle type) has relatively little impact on the efficacy of these herbicides. Proper nozzle selection can result in control of Chloris spp., a hard to control weed species, while reducing the occurrence of spray drift to nearby sensitive areas.
Recent advances in biotechnology have resulted in crops that are tolerant to the synthetic auxin 2,4-D, expanding the weed management versatility of this herbicide. With potential expansions of use, concerns have been raised about the increased risk of herbicide drift, leading to damage to nontarget crops. A field-scale study was conducted with the objective to measure drift deposition and the potential for drift reduction conferred by a proprietary pre-mixture formulation of 2,4-D choline salt plus glyphosate dimethylammonium salt compared to an in-tank mixture of 2,4-D dimethylamine salt plus glyphosate potassium salt. Treatments were made with field-scale spray equipment under typical application conditions in McCook, NE, using three widely used nozzle tips. Deposition was captured in triplicate downwind collector lines and assayed for tracer dye and 2,4-D. In comparison to the in-tank mixture, the pre-mixture formulation exhibited lower downwind depositions when applied through a flat-fan (TeeJet Extended Range; XR) and air induction (TeeJet Air Induction Extended Range; AIXR) nozzles, but not with a pre-orifice (TeeJet TurboTeeJet Induction; TTI) nozzle. Based upon median deposition at 30 m downwind, the pre-mixture formulation reduced drift by 62% and 91%, for the XR and AIXR nozzles, respectively. From a drift reduction perspective, the pre-mixture formulation performance with the AIXR nozzle was equivalent to a much coarser TTI nozzle while still offering sufficient foliar coverage for acceptable weed control.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
This study assessed bioavailability and utilisation of vitamin D3 in two feeding trials using young, growing Sprague–Dawley male rats. Trial one fed animals standard AIN-93G diet (casein protein) containing no vitamin D3 and goat or cow skimmed milk supplemented with vitamin D3. Trial two fed animals modified dairy-free AIN-93G diet (egg albumin) containing no vitamin D3 and goat or cow skimmed or full-fat milk supplemented with vitamin D3. Control groups received AIN-93G diets with or without vitamin D, and water. At 8 weeks of age, blood samples were collected for vitamin and mineral analysis, and femurs and spines were collected for assessment of bone mineralisation and strength. In both trials, analyses showed differences in bioavailability of vitamin D3, with ratios of serum 25-hydroxyvitamin D3 to vitamin D3 intake more than 2-fold higher in groups drinking supplemented milk compared with groups fed supplemented solid food. Bone mineralisation was higher in groups drinking supplemented milk compared with groups fed supplemented solid food, for both trials (P<0·05). There was no difference in the parameters tested between skimmed milk and full-fat milk or between cow milk and goat milk. Comparison of the two trials suggested that dietary protein source promoted bone mineralisation in a growing rat model: modified AIN-93G with egg albumin produced lower bone mineralisation compared with standard AIN-93G with casein. Overall, this study showed that effects of vitamin D3 deficiency in solid diets were reversed by offering milk supplemented with vitamin D3, and suggests that using milk as a vehicle to deliver vitamin D is advantageous.
Low and variable egg quality remains a major issue in aquaculture impeding a reliable and continuous supply of larvae, particularly in emerging species, such as pikeperch, Sander lucioperca. We assessed the influence of batch-specific egg parameters (fatty acid (FA) profiles, cortisol content) on embryo life-stages until hatching (survival at 2, 24, 48, 72 h post fertilization (hpf), hatching rate) in an integrated study under commercial hatchery conditions (44 egg batches). Embryo mortality was elevated until 48 hpf (average 9.8% mortality between 2 and 48 hpf). Embryos surviving until 48 hpf were very likely (98.5%) to hatch successfully. The inherent egg FA composition was variable in-between batches. Total FA content ranged form 66.1 to 171.7 µg/mg (dry matter) total FA. Whereas specific FA ,18 : 0 and 20 : 5(n-3) (eicosapentaenoic acid) of the polar fraction and the ratio of 22 : 6(n-3) (docosahexaenoic acid) to 20 : 5(n-3) within the neutral fraction, were significantly correlated with early embryo development, contents of the respective FA did not differ between high (>90% hatching rate), mid (70% to 90% hatching rate) and low (<70% hatching rate) quality egg batches. Late embryo development and hatching were relatively independent of the FA profiles highlighting stage-dependent influences especially during early embryogenesis. Cortisol levels ranged from 22.7 to 293.2 ng/ml and did not directly explain for mortalities. However, high cortisol was associated with a lower content of specific FA, in particular highly unsaturated FA. These results demonstrate the magnitude of inter-individual differences in the batch-specific biochemical egg composition under stable hatchery conditions and suggest a stress-mediated lack of essential FA, which in turn affects early embryo survival. Surprisingly, embryos are able to cope well with a broad range of inherent egg parameters, which limits their predictive potential for egg quality in general. Still, specific FA profiles of high quality egg batches have potential for formulating species-specific broodstock diets and improving reproductive management in pikeperch.
Drift reduction technologies aim to eliminate the smaller droplets that occur with some sprays because these small droplets can move off-target in the wind. Commonly used drift reduction technologies such as air-induction nozzles and spray additives impact on reducing off-target movement is well documented, however, the impact on herbicide penetration into an established crop canopy is not well known. This experiment evaluated the canopy penetration and efficacy of glyphosate treatments applied using four nozzle types (XR11005, AIXR11005, AITTJ11005, and TTI11005), two carrier volume rates (94 and 187 L ha-1), and glyphosate applications with and without a commercial drift reducing adjuvant. Applications were made to corn and soybean fields using glyphosate applied at 1.26 kg ae ha-1 with liquid ammonium sulfate at 5% v/v. A rhodamine dye was added (0.025% v/v) to the spray tank of each mixture as a tracer. MylarTM cards were placed in the field above the canopy, in the middle canopy, and on the ground for corn and above and below canopy for soybean. Five cards were at each position in the canopy arranged across the crop row. The addition of a drift reducing adjuvant did not impact canopy penetration. Doubling the carrier volume increased the amount of penetration proportionally and as such the percent reduction was not different. The TTI11005 nozzle had the greatest amount of spray penetration (28%) in the soybean canopies and the XR nozzle had the greatest amount (50%) in the corn canopies. Deposition across the row, beginning in-between the row crop and ending in the row of the crop was 44, 18, and 8% for soybean and 59, 50, and 36% for corn. For both crops, more than half of the herbicide application was captured in the crop canopy. Proper nozzle selection for canopy type can increase herbicide penetration and increasing the carrier volume will increase penetration proportionally.