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Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.
Aims
The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs.
Method
An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health.
Results
Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general.
Conclusion
The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.
Unhealthy food environments are major drivers of obesity and diet-related diseases(1). Improving the healthiness of food environments requires a widespread organised response from governments, civil society, and industry(2). However, current actions often rely on voluntary participation by industry, such as opt-in nutrition labelling schemes, school/workplace food guidelines, and food reformulation programmes. The aim of the REFORM study is to determine the effects of the provision of tailored support to companies on their nutrition-related policies and practices, compared to food companies that are not offered the programme (the control). REFORM is a two-country, parallel cluster randomised controlled trial. 150 food companies were randomly assigned (2:1 ratio) to receive either a tailored support intervention programme or no intervention. Randomisation was stratified by country (Australia, New Zealand), industry sector (fast food, other packaged food/beverage companies), and company size. The primary outcome is the nutrient profile (measured using Health Star Rating [HSR]) of foods and drinks produced by participating companies at 24 months post-baseline. Secondary outcomes include company nutrition policies and commitments, the nutrient content (sodium, sugar, saturated fat) of products produced by participating companies, display of HSR labels, and engagement with the intervention. Eighty-three eligible intervention companies were invited to take part in the REFORM programme and 21 (25%) accepted and were enrolled. Over 100 meetings were held with company representatives between September 2021 and December 2022. Resources and tailored reports were developed for 6 touchpoints covering product composition and benchmarking, nutrition labelling, consumer insights, nutrition policies, and incentives for companies to act on nutrition. Detailed information on programme resources and preliminary 12-month findings will be presented at the conference. The REFORM programme will assess if provision of tailored support to companies on their nutrition-related policies and practices incentivises the food industry to improve their nutrition policies and actions.
Young children, especially those under one year of age, are at higher risk of choking on food due to their body’s immature physiology and chewing, swallowing and coughing ability(1). In 2020, the Ministry of Education mandated the Ministry of Health’s food-related choking guidance for babies and young children at early learning services (ELS), adding it to the licensing criteria(2). Some ELS managers reported that this policy may negatively influence the food and nutrition environment within ELS(3).This study aimed to assess the impact of the food-related choking policy on the food and nutrition environment within ELS. Data were collected using an online Qualtrics questionnaire from ELS in four District Health Board regions: Waikato, Bay of Plenty, Lakes, and Auckland (N = 1066), sourced from the Ministry of Education, Education Counts database. Responses were received from 179 ELS (17%) and most reported making changes due to the food-related choking guidance. The main changes were to the food provided by the ELS (75%), education for whānau/family (73%), and supervision of children (70%). Over half of the centres reported adjusting staff duties to allow for increased supervision of eating (60%) and changed/ceased celebrations or fundraisers (58%). Over half of the respondents (55%) reported that changes to reduce the risk of food-related choking had affected the ‘cultural kaupapa’ (plan/policy) of the ELS. A key theme from written responses was that centres had ‘not come together as whānau’, which refers to reduced hosting of centre events/celebrations within the centre and externally with children and whānau (families). The main reason appeared to be that the food restrictions in the guidance made the management of ‘shared kai (food)’ too difficult. Approximately two-thirds of centres (61%) reported removing foods from menus, and around half (49%) modified the texture of foods. Fifty-one per cent of ELS reported that there had been no change in parent-supplied food. The main foods removed from ELS menus were fruit, vegetables, hard crackers, sausages/other meats, and popcorn. Soft fruit, e.g., canned fruit, soft crackers, and soft meats (hamburger patties, mince, luncheon, and ham), were the main foods added to menus. ELS have responded to most of the new food-related choking guidance requirements regarding food provision, texture modification, and supervision; however, some ELS may need support to implement fully. Ceasing shared kai events at ELS has reduced opportunities to engage with whānau and limits cultural expression, connection and reciprocal learning and teaching about food and nutrition between the centre and whānau as outlined in Te Whariki Early Childhood Curriculum. Improved communication and support for parents and ELS to implement the recommendations for home and centre-supplied foods is needed. Together with sufficient funding for supervision and nutrition education to support children’s learning and cultural needs around food.
Paul's letters depict gentiles and Jews with different characteristics of sin. This article focuses on Paul's rhetoric about Jewish shortcomings and argues that he has an eschatological myth of Jewish sin: it is the period in the Jewish deity's plan when he has hardened his people into disobedience and disloyalty. While scholars have traditionally tried to connect Paul's ideas about Jewish sin to deficiencies of historical Jews, Paul's claims are primarily animated by his Jewish eschatological scheme and competitive rhetorical needs. Paul re-emerges as a Jewish writer within his competitive social landscape wherein ethnic differentiation was an expected way of imagining the human and divine realms.
The properties of multiphase flows are challenging to measure, and yet effective properties are fundamental to modelling and predicting flow behaviour. The current study is motivated by rheometric measurements of a gas-fluidized bed using a coaxial rheometer in which the fluidization rate and the rotational speed can be varied independently. The measured torque displays a range of rheological states: quasistatic, dense granular flow behaviour at low fluidization rates and low-to-moderate shear rates; turbulent toroidal-vortex flow at high shear rates and moderate-to-high fluidization rates; and viscous-like behaviour with rate-dependent torque at high shear rates and low fluidization or at low shear rates and high fluidization. To understand the solid-like to fluid-like transitions, additional experiments were performed in the same rheometer using single-phase liquid and liquid–solid suspensions. The fluidized bed experiments are modelled as a Bingham plastic for low fluidization rates, and as a shear-thinning Carreau liquid at high fluidization rates. The suspensions are modelled using the Krieger–Dougherty effective viscosity. The results demonstrate that, by using the effective properties, the inverse Bingham number marks the transition from solid-like to viscous-flow behaviour; a modified gap Reynolds number based on the thickness of the shear layer specifies the transition from solid-like to turbulent vortical flow; and a gap Reynolds number distinguishes viscous behaviour from turbulent vortical flow. The results further demonstrate that these different multiphase flows undergo analogous flow transitions at similar Bingham or Reynolds numbers and the corresponding dimensionless torques show comparable scaling in response to annular shear.
Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm, Ancylostoma caninum, that is resistant to 3 major classes of anthelmintics is characterized. Various drug assays were used to determine the resistance of BCR to thiabendazole, ivermectin, moxidectin and pyrantel pamoate. When compared to a drug-susceptible isolate of A. caninum, BCR was shown to be significantly resistant to all 4 of the drugs tested. Multiple single nucleotide polymorphisms have been shown to impart benzimidazole resistance, including the F167Y mutation in the β-tubulin isotype 1 gene, which was confirmed to be present in BCR through molecular analysis. The frequency of the resistant allele in BCR was 76.3% following its first passage in the lab, which represented an increase from approximately 50% in the founding hookworm population. A second, recently described mutation in codon 134 (Q134H) was also detected at lower frequency in the BCR population. Additionally, BCR exhibits an altered larval activation phenotype compared to the susceptible isolate, suggesting differences in the signalling pathways involved in the activation process which may be associated with resistance. Further characterization of this isolate will provide insights into the mechanisms of resistance to macrocyclic lactones and tetrahydropyrimidine anthelmintics.
Geophagy is the intentional consumption of earth. Although widely documented among vulnerable populations, including children and pregnant women, the causes and consequences of geophagy remain poorly understood. Relevant literature was, therefore, reviewed to describe geophagy across species, geographies, life stages, and disease states. After a brief consideration of hypothesized etiologies, the potential harmful and beneficial consequences of geophagy are described, considering current evidence for each. Data available to date suggest that the greatest potential risks of geophagy include toxicity or heavy metal poisoning, and diseases resulting from consumed clays binding nutrients and beneficial pharmaceuticals in the gut. Evidence also suggests that geophagy may be beneficial by protecting against harmful pathogens and toxins through two distinct physiological pathways. Future research should explore causal relationships between geophagy and iron deficiency, as well as investigate the biological and psychosocial conditions that govern geophagy.
Although remote neuropsychological assessments have become increasingly common, current research on the reliability and validity of scores obtained from remote at-home assessments are sparse. No studies have examined remote at-home administration of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) even though this battery is being used to track over 45,000 participants over time. This study aimed to determine whether remote UDS scores can be combined with in-person data by assessing whether rates of score changes over time (i.e., reliability) differed by modality and whether remote and in-person scores converge (i.e., validity).
Participants and Methods:
Data for UDS visits conducted from 09/2005 to 12/2021 from 43 Alzheimer’s Disease Research Centers were examined. We identified 311 participants (254 cognitively unimpaired, 7 impaired - not mild cognitive impairment, 25 mild cognitive impairment, 25 dementia) who completed 2 remote UDS visits 0.868 years apart (SD = 0.200 years). First, initial remote scores were correlated with most recent in-person scores. Second, we examined whether rates of change differed between remote and in-person assessments. Repeated-measure one-way ANOVA were used to compare rates calculated from the same individual from remote versus inperson assessments. We additionally identified a demographically- and visit-number-matched group of 311 participants with in-person UDS visits given that all remote visits occurred after in-person visits; one-way ANOVAs were used to compare remote rates to rates from in-person assessments from the matched in-person group. Finally, accuracy of remote scores were assessed by quantifying the difference between the actual remote scores and predicted scores based on repeated in-person assessments. These residual values were then divided by the maximum score to form error rates.
Results:
Remote UDS score on MoCA-blind, Craft story immediate and delayed recall, digits forward, digits backward, phonemic fluency (F, L, F + L), and semantic fluency (animals, vegetables, animals + vegetables) were all highly correlated (all ps < 0.001) with scores obtained from preceding in-person assessments. At the group level, within-subject comparisons between remote and in-person rates of change were not significantly different for 7/11 tests; between-subject comparisons were not significantly different for 10/11 tests. Vegetable fluency had slightly reduced rates of change with remote assessment compared to inperson assessments. Critically, remote scores were consistent with predicted scores based on the trajectory of each subject’s in-person assessments with group mean error rates ranging from 0.7% (Craft Delayed Recall) to 3.9% (Phonemic fluency - F).
Conclusions:
Our results demonstrate adequate reliability and convergent validity for remotely administered verbally based tests from the NACC UDS battery. Importantly, our findings provide some support for combining remote and in-person scores for studies that transitioned to remote testing due to COVID-19. However, future research is needed for tests with visual stimuli that assess visual memory, visuospatial function, and aspects of executive function.
As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).
Participants and Methods:
The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.
Results:
The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.
Conclusions:
Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.
There is a need to identify scalable cognitive paradigms that are sensitive enough to relate to Alzheimer's disease biomarkers (amyloid and tau) in the preclinical stage. Here, we determine whether initial performance and practice effects on the memory-focused Computerized Cognitive Composite (C3) relate to demographic variables, amyloid status [abnormal (A+), normal (A-)], and regional tau in clinically unimpaired (CU) older adults.
Participants and Methods:
We examined pre-randomization data from CU older adults screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. We focused on participants who completed the C3 (n=3287), most of whom completed an alternate version of the C3 again approximately 51 days later (n=4141), as well as a subset of preclinical AD participants (i.e., A+ CU) who completed the C3 and tau PET imaging with [18]F-flortaucipir (initial C3: n=354; repeat C3: n=343). C3 initial performance and practice effects were examined in relation to amyloid status (A+, A-) and continuous regional tau burden.
Results:
Initial C3 performance was associated with amyloid status [B(SE) = -0.075 (0.021), p < 0.001] across all participants, as well as tau burden in the medial temporal lobe (MTL) [B (SE) = -0.728 (0.220), p = 0.001], inferior temporal (IT) cortex [B (SE) = -0.782 (0.264), p = 0.003], and inferior parietal (IP) cortex [B (SE) = -0.721 (0.281), p = 0.011] amongst preclinical AD individuals. Short-term practice effects were also associated with reduced tau burden in MTL [B (SE) = -0.471 (0.202), p = 0.020], IT [B (SE) = -0.640 (0.240), p = 0.008], and IP [B( SE) = - 0.584 (0.255), p = 0.023] amongst preclinical AD participants, but were not associated with amyloid status [B (SE) = -0.018 (0.020), p = 0.348]. Critically, these effects with tau were only detected when baseline performance was accounted for presumably due to opposing influence from both practice effects and regression to the mean effects.
Conclusions:
This is the first study to show that performance on a brief cognitive battery administered in a multisite context is associated with both amyloid and tau among CU older adults. These findings suggest that computerized assessments may be a cost-effective and scalable approach for early detection efforts. Further, diminished practice effects on memory-based measures are associated with elevated tau burden in preclinical AD, suggesting that high-frequency cognitive testing collected over a short follow-up period may provide additional insights regarding early disease processes than single assessments.
Individuals with overweight or obesity are at a high risk for so-called ‘atypical’ or immunometabolic depression, with associated neurovegetative symptoms including overeating, fatigue, weight gain, and a poor metabolic profile evidenced e.g. by dyslipidemia or hyperglycemia. Research has generated preliminary evidence for a low-calorie diet (LCD) in reducing depressive symptoms. The aim of the current systematic review and meta-analysis is to examine this evidence to determine whether a LCD reduces depressive symptoms in people with overweight or obesity.
Methods
Eligible studies were identified through PubMed, ISI Web of Science, and PsycINFO until August 2023. Standardized mean differences (SMDs) were derived using random-effects meta-analyses for (1) pre-post LCD comparisons of depression outcomes, and (2) LCD v. no-diet-control group comparisons of depression outcomes.
Results
A total of 25 studies were included in the pre-post meta-analysis, finding that depression scores were significantly lower following a LCD (SMD = −0.47), which was not significantly moderated by the addition of exercise or behavioral therapy as a non-diet adjunct. Meta-regressions indicated that a higher baseline BMI and greater weight reduction were associated with a greater reduction in depression scores. The intervention-control meta-analysis (n = 4) found that overweight or obese participants adhering to a LCD showed a nominally lower depression score compared with those given no intervention (SMD = −0.29).
Conclusions
There is evidence that LCDs may reduce depressive symptoms in people with overweight or obesity in the short term. Future well-controlled intervention studies, including a non-active control group, and longer-term follow-ups, are warranted in order to make more definitive conclusions.
To learn about the perceptions of healthcare personnel (HCP) on the barriers they encounter when performing infection prevention and control (IPC) practices in labor and delivery to help inform future IPC resources tailored to this setting.
Design:
Qualitative focus groups.
Setting:
Labor and delivery units in acute-care settings.
Participants:
A convenience sample of labor and delivery HCP attending the Infectious Diseases Society for Obstetrics and Gynecology 2022 Annual Meeting.
Methods:
Two focus groups, each lasting 45 minutes, were conducted by a team from the Centers for Disease Control and Prevention. A standardized script facilitated discussion around performing IPC practices during labor and delivery. Coding was performed by 3 reviewers using an immersion-crystallization technique.
Results:
In total, 18 conference attendees participated in the focus groups: 67% obstetrician-gynecologists, 17% infectious disease physicians, 11% medical students, and 6% an obstetric anesthesiologist. Participants described the difficulty of consistently performing IPC practices in this setting because they often respond to emergencies, are an entry point to the hospital, and frequently encounter bodily fluids. They also described that IPC training and education is not specific to labor and delivery, and personal protective equipment is difficult to locate when needed. Participants observed a lack of standardization of IPC protocols in their setting and felt that healthcare for women and pregnant people is not prioritized on a larger scale and within their hospitals.
Conclusions:
This study identified barriers to consistently implementing IPC practices in the labor and delivery setting. These barriers should be addressed through targeted interventions and the development of obstetric-specific IPC resources.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Weeds and invasive plants know no borders and have collectively impacted many ecosystems worldwide, including croplands, forests, grasslands, rangelands, wetlands, and riparian areas. Losses continue to mount, affecting yield and productivity, species diversity, and ecosystem services, with both short- and long-term repercussions on the sustainability of plant and animal communities and the livelihoods of many. New and emerging invasive plants, along with many of the most intractable weeds, have undermined even the best control efforts, serving as a reminder of the constant need for improvements in science, application, and technology. One of the main reasons for the success of weeds and invasive plants is their ability to adapt to abiotic and biotic conditions, and research suggests that this will continue with minimal change.
COMP360 is a synthetic, proprietary, purified form of psilocybin in development for treatment-resistant depression (TRD) with FDA Breakthrough Therapy designation. In a recent phase IIb study, COMP360 psilocybin 25mg was superior to 1mg on change from baseline (CFB) to Week 3 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score (primary efficacy endpoint), when administered alongside psychological support. Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) total score (exploratory efficacy endpoint) showed similar results.
Objectives
To analyse changes in specific depression symptoms after psilocybin treatment in the aforementioned study, as measured by individual item scores on the MADRS and QIDS-SR16 (range 0-6 and 0-3).
Methods
Participants with TRD were randomised to single doses of psilocybin 25mg (n=79), 10mg (n=75), or 1mg (n=79). A remote, blinded rater assessed the MADRS at Baseline, Day 2 (the day post-psilocybin), and Weeks 1, 3, 6, 9, and 12. The QIDS-SR16 was self-rated at Baseline, Day 1, Day 2, and Weeks 1, 2, 3, 6, 9, and 12. At each time point, descriptive statistics were calculated for each MADRS and QIDS-SR16 individual item score.
Results
At Week 3, MADRS items with the largest differences in mean CFB in the 25mg arm were Inability to Feel, Apparent Sadness, Lassitude, and Reported Sadness. Greater improvement in the 25mg arm was apparent from Day 2 and remained to Week 12 (Lassitude remained to Week 6 only). On the QIDS-SR16, the item with the largest difference in mean CFB at Week 3 in the 25mg arm was in Feeling Sad and remained evident to Week 12 (Table 1).Table 1.
Item (mean CFB at Week 3 [standard deviation])
Psilocybin 25mg
Psilocybin 10mg
Psilocybin 1mg
MADRS - Inability to Feel
-1.8 [1.81]
-0.9 [1.54]
-0.8 [1.61]
MADRS - Apparent Sadness
-1.7 [1.94]
-1.1 [1.60]
-0.9 [1.62]
MADRS - Lassitude
-1.6 [1.81]
-1.2 [1.83]
-0.8 [1.58]
MADRS - Reported Sadness
-1.6 [1.95]
-1.0 [1.52]
-0.6 [1.53]
QIDS-SR16- Feeling Sad
-1.1 [1.08]
-0.8 [1.07]
-0.4 [0.91]
Conclusions
A single administration of COMP360 psilocybin therapy rapidly and dose-relatedly improved symptoms of depressed mood and anhedonia – the two key symptoms of depression. As anhedonia is predictive of poorer treatment response, and improvements in anhedonia correlate with improvements in functioning, it is important to understand the impact of treatments on this symptom.
Disclosure of Interest
G. Goodwin Shareolder of: COMPASS Pathways, P1Vital, and P1Vital products , Employee of: COMPASS Pathways, L. Marwood Shareolder of: COMPASS Pathways, Employee of: COMPASS Pathways, S. Mistry Employee of: COMPASS Pathways, A. Nowakowska Employee of: COMPASS Pathways, H. Simmons Employee of: COMPASS Pathways, J. Tsai Employee of: COMPASS Pathways, S. Williams Employee of: COMPASS Pathways, M. Young Shareolder of: COMPASS Pathways, Employee of: COMPASS Pathways, E. Malievskaia Employee of: COMPASS Pathways