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Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
The Magellanic Stream (MS), a tail of diffuse gas formed from tidal and ram pressure interactions between the Small and Large Magellanic Clouds (SMC and LMC) and the Halo of the Milky Way, is primarily composed of neutral atomic hydrogen (HI). The deficiency of dust and the diffuse nature of the present gas make molecular formation rare and difficult, but if present, could lead to regions potentially suitable for star formation, thereby allowing us to probe conditions of star formation similar to those at high redshifts. We search for $\text{HCO}^{+}$, HCN, HNC, and C$_2$H using the highest sensitivity observations of molecular absorption data from the Atacama Large Millimeter Array (ALMA) to trace these regions, comparing with HI archival data from the Galactic Arecibo L-Band Feed Array (GALFA) HI Survey and the Galactic All Sky Survey (GASS) to compare these environments in the MS to the HI column density threshold for molecular formation in the Milky Way. We also compare the line of sight locations with confirmed locations of stars, molecular hydrogen, and OI detections, though at higher sensitivities than the observations presented here.
We find no detections to a 3$\sigma$ significance, despite four sightlines having column densities surpassing the threshold for molecular formation in the diffuse regions of the Milky Way. Here we present our calculations for the upper limits of the column densities of each of these molecular absorption lines, ranging from $3 \times 10^{10}$ to $1 \times 10^{13}$ cm$^{-2}$. The non-detection of $\text{HCO}^{+}$ suggests that at least one of the following is true: (i) $X_{\text{HCO}^{+}{}, \mathrm{MS}}$ is significantly lower than the Milky Way value; (ii) that the widespread diffuse molecular gas observed by Rybarczyk (2022b, ApJ, 928, 79) in the Milky Way’s diffuse interstellar medium (ISM) does not have a direct analogue in the MS; (iii) the HI-to-$\text{H}_{2}$ transition occurs in the MS at a higher surface density in the MS than in the LMC or SMC; or (iv) molecular gas exists in the MS, but only in small, dense clumps.
Helium or neopentane can be used as surrogate gas fill for deuterium (D2) or deuterium-tritium (DT) in laser-plasma interaction studies. Surrogates are convenient to avoid flammability hazards or the integration of cryogenics in an experiment. To test the degree of equivalency between deuterium and helium, experiments were conducted in the Pecos target chamber at Sandia National Laboratories. Observables such as laser propagation and signatures of laser-plasma instabilities (LPI) were recorded for multiple laser and target configurations. It was found that some observables can differ significantly despite the apparent similarity of the gases with respect to molecular charge and weight. While a qualitative behaviour of the interaction may very well be studied by finding a suitable compromise of laser absorption, electron density, and LPI cross sections, a quantitative investigation of expected values for deuterium fills at high laser intensities is not likely to succeed with surrogate gases.
We present the most sensitive and detailed view of the neutral hydrogen (${\rm H\small I}$) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ($1.6\,\mathrm{mJy\ beam}^{-1}$) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ (${\sim}10\,\mathrm{pc}$). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.
Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.
Aims
To explore the extent and nature of ‘treatment gaps’ (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.
Method
Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced.
Results
Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment.
Conclusions
There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.
In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
Sub-acute ruminal acidosis (SARA) can reduce the production efficiency and impair the welfare of cattle, potentially in all production systems. The aim of this study was to characterise measurable postmortem observations from divergently managed intensive beef finishing farms with high rates of concentrate feeding. At the time of slaughter, we obtained samples from 19 to 20 animals on each of 6 beef finishing units (119 animals in total) with diverse feeding practices, which had been subjectively classified as being high risk (three farms) or low risk (three farms) for SARA on the basis of the proportions of barley, silage and straw in the ration. We measured the concentrations of histamine, lipopolysaccharide (LPS), lactate and other short-chain fatty acids (SCFAs) in ruminal fluid, LPS and SCFA in caecal fluid. We also took samples of the ventral blind sac of the rumen for histopathology, immunohistopathology and gene expression. Subjective assessments were made of the presence of lesions on the ruminal wall, the colour of the lining of the ruminal wall and the shape of the ruminal papillae. Almost all variables differed significantly and substantially among farms. Very few pathological changes were detected in any of the rumens examined. The animals on the high-risk diets had lower concentrations of SCFA and higher concentrations of lactate and LPS in the ruminal fluid. Higher LPS concentrations were found in the caecum than the rumen but were not related to the risk status of the farm. The diameters of the stratum granulosum, stratum corneum and of the vasculature of the papillae, and the expression of the gene TLR4 in the ruminal epithelium were all increased on the high-risk farms. The expression of IFN-γ and IL-1β and the counts of cluster of differentiation 3 positive and major histocompatibility complex class two positive cells were lower on the high-risk farms. High among-farm variation and the unbalanced design inherent in this type of study in the field prevented confident assignment of variation in the dependent variables to individual dietary components; however, the CP percentage of the total mixed ration DM was the factor that was most consistently associated with the variables of interest. Despite the strong effect of farm on the measured variables, there was wide inter-animal variation.
Precise timing of muscle contractions is an important prerequisite for motor control and one to which the cerebellum contributes. Braitenberg et al.'s detailed timing hypotheses relate only to a subset of the known features of the organisation of the cerebellum. However, the cerebellar architecture clearly supports the “tidal waves” that are central to the authors' proposal and such tidal waves are very likely to contribute to its functions.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
Multi-layer reconstruction has become standard in endoscopic skull base surgery. The inlay component used can vary among autografts, allografts, xenografts and synthetics, primarily based on surgeon preference. The short- and long-term outcomes of collagen matrix in skull base reconstruction are described.
Methods:
A case series of patients who underwent endoscopic skull base reconstruction with collagen matrix inlay were assessed. Immediate peri-operative outcomes (cerebrospinal fluid leak, meningitis, ventriculitis, intracranial bleeding, epistaxis, seizures) and delayed complications (delayed healing, meningoencephalocele, prolapse of reconstruction, delayed cerebrospinal fluid leak, ascending meningitis) were examined.
Results:
Of 120 patients (51.0 ± 17.5 years, 41.7 per cent female), peri-operative complications totalled 12.7 per cent (cerebrospinal fluid leak, 3.3 per cent; meningitis, 3.3 per cent; other intracranial infections, 2.5 per cent; intracranial bleeding, 1.7 per cent; epistaxis, 1.7 per cent; and seizures, 0 per cent). Delayed complications did not occur in any patients.
Conclusion:
Collagen matrix is an effective inlay material. It provides robust long-term separation between sinus and cranial cavities, and avoids donor site morbidity, but carries additional cost.
Fall applications of pronamide [3,5-dichloro(N-1,1-dimethyl-2-propynyl)benzamide] control or suppress quackgrass [Agropyron repens (L.) Beauv.] in established alfalfa (Medicago sativa L.). Studies were initiated to evaluate benefits of pronamide usage in areas where quackgrass is a problem. Alfalfa swards severely infested with quackgrass were treated with pronamide. Forage quality of first cutting alfalfa was significantly improved with pronamide usage, but second and third cutting forage quality was not greatly affected. First cutting hay from pronamide-treated and untreated areas was fed to goats and dairy cows in feeding trials. Animal intake of total forage dry matter, digestible dry matter, and digestible crude protein was increased with pronamide usage. A reduction in need for supplemental protein, an increase in efficiency in dry matter conversion into milk, and a 20% increase in milk production resulted from controlling quackgrass in alfalfa with pronamide.
Pea (Pisum sativum L. ‘Elf’) root rot suppression by dinitroaniline herbicides could not be explained by a direct effect on the host. Pre-incubation of pea roots with 0.1 ppmw of oryzalin (3,5-dinitro-N4,N4-dipropylsulfanilamide) or trifluralin (α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine) in solution culture did not alter their resistance to root rot. Furthermore, 0.1 ppmw of oryzalin or trifluralin did not alter the exudation of electrolytes or α-amino compounds from pea roots. Most of the dinitroaniline herbicides significantly inhibited mycelial radial growth of pathogen, Aphanomyces euteiches Drechs., at 1.0 ppmw and inhibited asexual spore production at 0.1 to 1.0 ppmw. Dinitramine (N4,N4-diethyl-α,α,α-trifluoro-3,5-dinitrotoluene-2,4-diamine), fluchloralin [N-(2-chloroethyl)-2,6-dinitro-N-propyl-4-(trifluoromethyl)aniline], and oryzalin inhibited A. euteiches mycelial growth and asexual reproduction more effectively than the other dinitroaniline herbicides studied. The production of motile zoospores, the infecting propagule of the pathogen, was the most sensitive stage in the life cycle and was completely inhibited by 0.01 ppmw of all dinitroaniline herbicides tested. Since this concentration is below that estimated in the soil solution at registered rates of application, inhibition of motile zoospore production is sufficient to explain root rot suppression. Inhibition of pathogen motility resulted in a 2-week delay in the infection of pea roots. This delay allowed sufficient additional plant growth that the peas could better withstand the effects of subsequent disease development.
Field studies were conducted in Michigan, Minnesota, and Wisconsin to explore interactions among DPX-V9360 herbicide applied postemergence, terbufos insecticide applied as an in-furrow treatment, and the environment. Field corn (‘Pioneer 3751’) and sweet corn (‘Jubilee’) were planted with and without an in-furrow application of terbufos. DPX-V9360 was applied postemergence when the corn was in the 4- to 6-leaf stage at 0, 35, 70, 140, and 280 g ai ha-1 with nonionic surfactant and 28% N fertilizer solution. Crop response to DPX-V9360 was similar at all three locations, varying only in magnitude of injury. Crop injury was greater with Jubilee sweet corn than with Pioneer 3751 field corn. Injury to both hybrids increased as DPX-V9360 application rate increased. Application of terbufos increased injury from DPX-V9360 to both hybrids. Significant yield reduction did not occur with either hybrid when DPX-V9360 was applied at rates of 140 g ha-1 or less and no terbufos was applied.
Field studies were conducted in 1985 and 1986 to determine the influence of herbicide rate, carrier, and carrier volume on off-site movement of clomazone {2-[2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxalidinone} using sunflower (Helianthus annuus L. ‘HY-894’) and wheat (Triticum aestivum L. ‘Caldwell’) as indicator plants. Clomazone applied at the lowest rate (0.56 kg ai/ha) had less off-site movement than higher rates. Off-site movement was similar among water carrier volumes applied at each clomazone rate but was less when clomazone was impregnated onto dry fertilizer.
Field experiments were conducted in Michigan, Minnesota, and Wisconsin in 1990 to explore interactions between nicosulfuron applied POST and terbufos insecticide at 0.06 or 0.11 g ai/m of row applied in-furrow on ‘Pioneer 3751’ field corn and ‘Jubilee’ sweet corn. Nicosulfuron at 0, 70, and 140 g ai/ha plus nonionic surfactant and 28% nitrogen fertilizer was applied to both corn types. Field corn response to nicosulfuron and terbufos was similar at all locations, whereas sweet corn injury varied with location. Nicosulfuron injured field corn more when applied at the four-leaf than the three-leaf stage. Injury to both corn types increased as nicosulfuron rate increased or when applied following terbufos. Nicosulfuron at 140 g/ha without terbufos did not reduce yield of either corn type; however, corn previously treated in-furrow with terbufos reduced yield.
Sweet corn tolerance to nicosulfuron as affected by interactions between nicosulfuron applied postemergence (POST), sweet corn hybrid, and rootworm insecticide applied at planting was determined in 1992 and 1993 field experiments. Sweet corn vigor was reduced as nicosulfuron rate increased from 35 to 140 g ai/ha. Sweet corn vigor was reduced 4% more by nicosulfuron with oil emulsifier mixture than nicosulfuron with non-ionic surfactant one week after treatment (WAT). Adjuvant selection did not influence nicosulfuron injury to sweet corn 2 WAT. Nicosulfuron applied postemergence directed (PDIR) caused less sweet corn injury than nicosulfuron applied broadcast POST. ‘Jubilee’ sweet corn was more sensitive to nicosulfuron and insecticide treatments than ‘Excellency’ or ‘Green Giant 40.’ Nicosulfuron reduced sweet corn vigor twice as much when terbufos was applied at planting compared to no insecticide at planting. Neither chlorpyrifos or chlorethoxyfos at planting increased sweet corn injury due to nicosulfuron compared to no insecticide. Excellency and Green Giant 40 yields were not reduced by any treatment. Yields were reduced only when nicosulfuron was applied to Jubilee treated with terbufos. Jubilee yield reduction from nicosulfuron and terbufos was prevented by applying nicosulfuron PDIR.
Field experiments were conducted in Michigan, Minnesota, and Wisconsin to evaluate injurious interactions between nicosulfuron herbicide applied POST and nine insecticides applied at planting on ‘Pioneer 3751’ field corn in 1991. Insecticides were applied in-furrow, T-band, and surface band at planting. Corn injury from nicosulfuron and terbufos applications was more severe in Wisconsin than in Michigan. No corn injury was observed in Minnesota. Terbufos 15% ai granule (15G) or 20% ai controlled release granule (20CR) increased nicosulfuron injury to corn in Wisconsin. Nicosulfuron at 35 g ai/ha caused the greatest vigor reduction following terbufos 15G, intermediate vigor reduction following terbufos 20CR, phorate 20G, or phorate 20CR, and the least vigor reduction following fonofos, chlorpyrifos, chlorethoxyfos, tefluthrin, or carbofuran in Wisconsin.
Nine substituted dinitronaline herbicides were studied to determine their effectiveness in controlling common root rot of peas (Pisum sativum L.) caused by Aphanomyces euteiches Drechs. under field conditions. Most of the dinitroaniline herbicide treatments increased plant stand, plant fresh weight, and shelled pea yield due to root rot suppression in each of the three years studied. Weed control was good in all plots and did not contribute to yield differences. Root rot suppression and crop injury were the primary determinants of yields. The greatest yield increases when compared with the weeded control were 82% for 0.56 kg/ha of dinitramine (N4,N4-diethyl-α,α,α-trifluoro-3,5-dinitrotoluene-2,4-diamine) in 1974, 80% for 0.84 kg/ha of fluchloralin [N-(2-chloroethyl)-2,6-dinitro-N-propyl-4-(trifluoromethyl) aniline] in 1975, and 26% for 1.68 kg/ha of pendimethalin [N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine] in 1976. The best average yield increases over all years were 54% for the combination of trifluralin (α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine) and oryzalin (3,5-dinitro-N4,N4-dipropylsulfanilamide) at 0.56 + 0.56 kg/ha, 49% for fluchloralin at 0.84 kg/ha, and 43% for pendimethalin at 0.84 kg/ha. Annual applications of 0.84 kg/ha of trifluralin delayed the rate of pathogen infestation of a field repeatedly planted to peas.