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Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims
To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
Method
The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).
Results
In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).
Conclusion
Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.
The functioning and richness of marine systems (and biological interactions such as parasitism) are continuously influenced by a changing environment. Using hierarchical modelling of species communities (HMSC), the presence and abundance of multiple parasite species of the black-spotted croaker, Protonibea diacanthus (Sciaenidae), was modelled against environmental measures reflecting seasonal change. Protonibea diacanthus were collected in three seasons across 2019–2021 from four locations within the waters of the Northern Territory, Australia. The length of P. diacanthus proved to have a strong positive effect on the abundance of parasite taxa and overall parasitic assemblage of the sciaenid host. This finding introduces potential implications for parasitism in the future as fish body size responds to fishing pressure and climate changes. Of the various environmental factors measured during the tropical seasons of northern Australia, water temperature and salinity changes were shown as potential causal factors for the variance in parasite presence and abundance, with changes most influential on external parasitic organisms. As environmental factors like ocean temperature and salinity directly affect parasite–host relationships, this study suggests that parasite assemblages and the ecological functions that they perform are likely to change considerably over the coming decades in response to climate change and its proceeding effects.
Most of the Ross Sea has been designated a marine protected area (MPA), proposed ‘to protect ecosystem structure and function’. To assess effectiveness, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) selected Adélie (Pygoscelis adeliae) and emperor (Aptenodytes forsteri) penguins, Weddell seals (Leptonychotes weddellii) and Antarctic toothfish (Dissostichus mawsoni) as ecosystem change ‘indicator species’. Stable for decades, penguin and seal populations increased during 1998–2018 to surpass historical levels, indicating that change in ecosystem structure and function is underway. We review historical impacts to population trends, decadal datasets of ocean climate and fishing pressure on toothfish. Statistical modelling for Adélie penguins and Weddell seals indicates that variability in climate factors and cumulative extraction of adult toothfish may explain these trends. These mesopredators, and adult toothfish, all prey heavily on Antarctic silverfish (Pleuragramma antarcticum). Toothfish removal may be altering intraguild predation dynamics, leading to competitive release of silverfish and contributing to penguin and seal population changes. Despite decades of ocean/weather change, increases in indicator species numbers around Ross Island only began once the toothfish fishery commenced. The rational-use, ecosystem-based viewpoint promoted by CCAMLR regarding toothfish management needs re-evaluation, including in the context of the Ross Sea Region MPA.
Cognitive behavioural therapy (CBT) is an effective treatment for depression, but a significant minority of clients are difficult to treat, including those with histories of relational trauma. The model of Beck et al. (1979) proposes that adverse childhood experiences lead to negative core beliefs, and these create a susceptibility to depression. However, Beck’s model does not identify trauma as a subset of adverse experiences. An alternative view is that traumatised clients internalise conflicting representations of self and it is conflict, interacting with trauma memories, that creates a vulnerability for depression. In this formulation, methods from the treatment of post-traumatic stress disorder (PTSD) could be incorporated into the treatment of depression, to emotionally process trauma memories and resolve self-identity conflicts. The aims of this study were to: (1) report the treatment of a 67-year-old man with recurrent depression and a history of prolonged relational trauma, and (2) to explore how memory processing from the treatment of PTSD can be incorporated into the treatment of recurrent depression. A single case observational design was used in the long-term treatment of a depressed traumatised client. The client received 47 individual sessions over 19 months in routine clinical practice in a tertiary CBT service. He completed repeated measures of mood, memory intrusions and sleep disruption. The client responded well to treatment with clinically significant improvements across measures of mood, memory and sleep. The effects were sustained over an 18-month follow-up. Memory processing was successfully integrated into a high-intensity treatment for recurrent depression. This is a promising approach for depressed clients with histories of relational trauma.
Key learning aims
(1) To consider how imaginal reliving can be incorporated into CBT for recurrent depression, when relational trauma is present.
(2) To consider the cognitive processing mode of depressed traumatised clients when appraising beliefs about self and others.
(3) To consider vulnerability to depression based on intrusive memories and conflicting self-representations, not only core beliefs.
Among the longest Antarctic biological time series is that of Adélie penguin Pygoscelis adeliae population size at Cape Royds, 1955 to the present. Demographic trends over the 66 years fall into five periods: 1) decrease then recovery due to control of tourism from McMurdo Station/Scott Base; 2) further increase responding to the removal of > 20 000 trophically competing Antarctic minke whales Balaenoptera bonaerensis from the colony's wintering area; 3) stabilization but not decrease upon the ban of whaling in 1982, and whale recovery, owing to increased winds facilitating McMurdo Sound Polynya presence (easier ocean access during nesting); 4) decrease in 2001–2005 when two mega-icebergs, B15A/C16, opposed the wind effect by increasing sea-ice cover, thus limiting ocean access; and 5) after iceberg departure, minimal recovery due to the increased velocity of the wind-generated Ross Gyre reducing penguin breeding probability. A multivariant model using 1998–2018 data confirmed the roles of gyre speed (negative) and open water (positive) in colony growth. Additional negative influence came from high nest predation by south polar skuas Stercorarius maccormicki, reducing chick production, as well as perhaps increased trophic competition from nearby Weddell seals Leptonychotes weddellii. Clearly, long time series increase our understanding of penguin population dynamics responding to a complexity of factors.
To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).
Participants and Methods:
Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.
Results:
pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).
Conclusions:
Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
Aims
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
Method
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
Results
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Conclusions
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.
Methods:
This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.
Key Results:
A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.
Conclusions:
The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.
This article reports findings from a study that sought to identify barriers to music and music education in the UK. Emerging from empirical research involving n = 723 participants and clarified by an evidence base of over 10,000 research participants, the key findings presented in this paper relate to pupil and participant voice and involvement, location as a sub-theme of diversity and inclusion, collaboration and transition points. The research is contextualised by twenty years of policy initiatives seeking to address barriers to music learning. The article provides an overview of the research study before presenting the rich data that emerged within each theme reported. Research participant voice is used as much as possible to enable the reader to consider, reflect and interpret the data in a way that is meaningful for their own context. The paper concludes by asking why after 20 years of policy initiatives, research and evaluation the same barriers still exist and, as we emerge from the pandemic, suggests that this research provides a compelling case that now is the time for change.
Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.
Aims
We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.
Method
A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.
Results
We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.
Conclusions
We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.
A central area of current philosophical debate in the foundations of mathematics concerns whether or not there is a single, maximal, universe of set theory. Universists maintain that there is such a universe, while Multiversists argue that there are many universes, no one of which is ontologically privileged. Often model-theoretic constructions that add sets to models are cited as evidence in favor of the latter. This paper informs this debate by developing a way for a Universist to interpret talk that seems to necessitate the addition of sets to V. We argue that, despite the prima facie incoherence of such talk for the Universist, she nonetheless has reason to try and provide interpretation of this discourse. We present a method of interpreting extension-talk (V-logic), and show how it captures satisfaction in ‘ideal’ outer models and relates to impredicative class theories. We provide some reasons to regard the technique as philosophically virtuous, and argue that it opens new doors to philosophical and mathematical discussions for the Universist.
Burkart et al. conflate the domain-specificity of cognitive processes with the statistical pattern of variance in behavioural measures that partly reflect those processes. General intelligence is a statistical abstraction, not a cognitive trait, and we argue that the former does not warrant inferences about the nature or evolution of the latter.
The effect of barley seeding rate and row spacing, and triallate, diclofop, and difenzoquat herbicide rate on barley grain yield and quality, and wild oat control were evaluated in field experiments near Bonners Ferry, Idaho, in 1989 and 1990. The purpose of the study was to develop integrated control strategies for wild oat in spring barley. Barley row spacing (9 and 18 cm) did not affect barley grain yield. Barley grain yield was greatest when barley was seeded at 134 or 201 kg ha–1 compared to 67 kg ha–1. Wild oat control increased as wild oat herbicide rate increased and barley grain yield was greatest when wild oat herbicides were applied. However, barley grain yield was similar when wild oat biomass was reduced by either 65 or 85% by applications of half and full herbicide rates, respectively. Net return was greatest when the half rate of herbicide was applied to 100 wild oat plants per m2 and was greatest when half or full herbicide rates were applied to 290 wild oat plants per m2. Net return increased when the seeding rate was increased to 134 or 201 kg ha–1 when no herbicide was applied and when 290 wild oat plants per m2 were present.
This paper examines the efficiency of a sample of Great Plains grain marketing and farm supply cooperatives during 1988 to 1992. In general, larger cooperatives were more X-efficient and scale efficient. Labor tended to be under-utilized and capital over-utilized. Petroleum product sales and fertilizer sales were negatively related to overall efficiency. Sales of goods other than grain, fertilizer, agricultural chemicals, petroleum products, and feed was positively related to overall efficiency. Overall efficiency was significantly correlated with the rate of return to assets.
We describe a versatile infrared camera/spectrograph, IRIS, designed and constructed at the Anglo-Australian Observatory for use on the Anglo-Australian Telescope. A variety of optical configurations can be selected under remote control to provide several direct image scales and a few low-resolution spectroscopic formats. Two cross-dispersed transmission echelles are of novel design, as is the use of a modified Bowen-Burch system to provide a fast f/ratio in the widest-field option. The drive electronics includes a choice of readout schemes for versatility, and continuous display when the array is not taking data, to facilitate field acquisition and focusing.
The linearity of the detector has been studied in detail. Although outwardly good, slight nonlinearities prevent removal of fixed-pattern noise from the data without application of a cubic linearising function.
Specific control and data-reduction software has been written. We describe also a scanning mode developed for spectroscopic imaging.
Farm supply cooperatives are an important component of the retail agribusiness industry in the United States. The objective of this research is to identify financial variables that are determinants of return on equity in these cooperatives. Firm effects are important and their effect is the result of managerial decision making and director policy. The estimated coefficient on asset size was not statistically significant, suggesting that return on equity is invariant to size over this time period.
The aim of this research was to compare associations of self-perceived successful aging (SPSA) among Young-Old (Y-O; age 50–74 years) versus Old-Old (O-O; 75–99 years) community-dwelling adults. To our knowledge, this is the first study to compare respondents’ self-perceptions of successful aging among O-O relative to Y-O adults.
Methods:
Participants included 365 Y-O and 641 O-O adults. The two age groups were compared in terms of the association of SPSA with other preselected measures including sociodemographic information, physical and mental functioning, objective and subjective cognitive functioning, emotional health, and positive psychological constructs.
Results:
The O-O group reported higher levels of SPSA than the Y-O group. In multiple regression modeling examining predictors of SPSA in each group, there was a tendency toward lower associations in the O-O group overall. Most notably, the associations between physical and mental functioning with SPSA were significantly lower in the O-O versus Y-O group. There were no associations with SPSA that were significantly higher in the O-O versus Y-O group.
Conclusion:
The lower predictive power of physical and mental functioning on SPSA among O-O relative to Y-O adults is particularly noteworthy. It is apparent that SPSA is a multidimensional construct that cannot be defined by physical functioning alone. Continuing to clarify the underlying factors impacting SPSA between groups may inform tailored interventions to promote successful aging in Y-O and O-O adults.