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Research on nutraceutical and dietary interventions in psychiatry has grown substantially, but progress is hindered by methodological inconsistencies and limited reporting standards. To address this, the International Society for Nutritional Psychiatry Research presents the first guidelines on clinical trial design, conduct, and reporting for future clinical trials in this area. Recommendations were developed using a Delphi process including eighteen researchers with considerable clinical trial expertise and experience in either methodology, nutraceutical, or dietary interventions in psychiatry. These guidelines provide forty-nine recommendations for clinical trial design and outcomes, five for trial reporting, and seven for future research priorities. The recommendations included in these guidelines are designed to inform both nutraceutical and dietary clinical trial interventions in Nutritional Psychiatry. Common themes include an emphasis on the importance of a multidisciplinary research team and integration of co-design processes into the conduct and design of clinical research, methods to improve transparency and replicability of trial outcomes, and measures to address common biases in nutrition trials. Furthermore, we provide recommendations for future research including examining a greater variety of nutraceutical and dietary interventions, scalable delivery models, effectiveness and implementation studies, and the need to investigate these interventions in the prevention and management of less studied psychiatric conditions (e.g. schizophrenia and bipolar disorder). Recommendations included within these guidelines are intended to improve the rigor and clinical relevance of ongoing and future clinical trials in Nutritional Psychiatry.
Synaptotagmin-9 (Syt9) is a Ca2+ sensor mediating fast synaptic release expressed in various parts of the brain. The presence and role of Syt9 in retina is unknown. We found evidence for Syt9 expression throughout the retina and created mice to conditionally eliminate Syt9 in a cre-dependent manner. We crossed Syt9fl/fl mice with Rho-iCre, HRGP-Cre, and CMV-Cre mice to generate mice in which Syt9 was eliminated from rods (rodSyt9CKO), cones (coneSyt9CKO), or whole animals (CMVSyt9). CMVSyt9 mice showed an increase in scotopic electroretinogram (ERG) b-waves evoked by bright flashes with no change in a-waves. Cone-driven photopic ERG b-waves were not significantly different in CMVSyt9 knockout mice and selective elimination of Syt9 from cones had no effect on ERGs. However, selective elimination from rods decreased scotopic and photopic b-waves as well as oscillatory potentials. These changes occurred only with bright flashes where cone responses contribute. Synaptic release was measured in individual rods by recording anion currents activated by glutamate binding to presynaptic glutamate transporters. Loss of Syt9 from rods had no effect on spontaneous or depolarization-evoked release. Our data show that Syt9 acts at multiple sites in the retina and suggest that it may play a role in regulating transmission of cone signals by rods.
This paper explores the feasibility of a break-even-class mirror referred to as BEAM (break-even axisymmetric mirror): a neutral-beam-heated simple mirror capable of thermonuclear-grade parameters and $Q\sim 1$ conditions. Compared with earlier mirror experiments in the 1980s, BEAM would have: higher-energy neutral beams, a larger and denser plasma at higher magnetic field, both an edge and a core and capabilities to address both magnetohydrodynamic and kinetic stability of the simple mirror in higher-temperature plasmas. Axisymmetry and high-field magnets make this possible at a modest scale enabling a short development time and lower capital cost. Such a $Q\sim 1$ configuration will be useful as a fusion technology development platform, in which tritium handling, materials and blankets can be tested in a real fusion environment, and as a base for development of higher-$Q$ mirrors.
Understanding how selective logging affects biodiversity is crucial to planning cost-effective conservation strategies in tropical forests, yet there is limited understanding of its impacts on fauna functional diversity in the tropical Americas. We assessed how selective logging intensification and time since logging influence multiple metrics of fauna functional integrity in the Brazilian Amazon by collecting bird and dung beetle data within 48 logging management units that had experienced varying exploitation intensities between 1.5–2.0 and 5.0–6.0 years before the faunal surveys. We investigated assemblage responses and used functional attributes to assess changes in functional diversity, specialization, originality and species rarity. Using point counts and pitfall traps, we collected 5081 records of 182 bird species and 7892 dung beetles from 45 species. Logging intensification led to significant declines in most dung beetle responses and bird body mass, whereas time since logging was a key driver of dung beetle and bird functional and taxonomic diversity. Our study presents novel empirical evidence of how logging intensification effects vary across taxa, ecological metrics and time since logging, which is key to informing forest conservation and further investigating environmental degradation impacts on tropical biodiversity.
The Wisconsin high-temperature superconductor axisymmetric mirror experiment (WHAM) will be a high-field platform for prototyping technologies, validating interchange stabilization techniques and benchmarking numerical code performance, enabling the next step up to reactor parameters. A detailed overview of the experimental apparatus and its various subsystems is presented. WHAM will use electron cyclotron heating to ionize and build a dense target plasma for neutral beam injection of fast ions, stabilized by edge-biased sheared flow. At 25 keV injection energies, charge exchange dominates over impact ionization and limits the effectiveness of neutral beam injection fuelling. This paper outlines an iterative technique for self-consistently predicting the neutral beam driven anisotropic ion distribution and its role in the finite beta equilibrium. Beginning with recent work by Egedal et al. (Nucl. Fusion, vol. 62, no. 12, 2022, p. 126053) on the WHAM geometry, we detail how the FIDASIM code is used to model the charge exchange sources and sinks in the distribution function, and both are combined with an anisotropic magnetohydrodynamic equilibrium solver method to self-consistently reach an equilibrium. We compare this with recent results using the CQL3D code adapted for the mirror geometry, which includes the high-harmonic fast wave heating of fast ions.
Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km × 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination ($\hat{\psi }_{{\rm north}}$ = 0.00, s.e. = 0.15), managed areas had low RABV occupancy ($\hat{\psi }_{{\rm managed}}$ = 0.20, s.e. = 0.29) and enzootic areas had the highest level of RABV occupancy ($\hat{\psi }_{{\rm south}}$ = 0.83, s.e. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained.
A wealth of recent research in comparative politics examines how spatial variation in historical conditions shapes modern political outcomes. In an article in the American Political Science Review, Homola, Pereira, and Tavits argue that Germans who live nearer to former Nazi concentration camps are more likely to display out-group intolerance. Clarifying the conceptual foundations of posttreatment bias and reviewing the historical record on postwar state creation in Germany, we argue that state-level differences confound the relationship between distance to camps and out-group intolerance. Using publicly available European Values Survey data and electoral results from 2017, we find no consistent evidence that distance to camps is related to contemporary values. Our findings have implications for literatures on historical persistence, causal inference with spatial data, Holocaust studies, and outgroup tolerance.
Laboratory-based studies indicate that a major evolutionary advantage of bipedalism is enabling humans to walk with relatively low energy expenditure. However, such studies typically record subjects walking on even surfaces or treadmills that do not represent the irregular terrains our species encounters in natural environments. To date, few studies have quantified walking kinematics on natural terrains. Here we used high-speed video to record marker-based kinematics of 21 individuals from a Tsimane forager–horticulturalist community in the Bolivian Amazon walking on three different terrains: a dirt field, a forest trail and an unbroken forest transect. Compared with the field, in the unbroken forest participants contacted the ground with more protracted legs and flatter foot postures, had more inclined trunks, more flexed hips and knees, and raised their feet higher during leg swing. In contrast, kinematics were generally similar between trail and field walking. These results provide preliminary support for the idea that irregular natural surfaces like those in forests cause humans to alter their walking kinematics, such that travel in these environments could be more energetically expensive than would be assumed from laboratory-based data. These findings have important implications for the evolutionary energetics of human foraging in environments with challenging terrains.
OBJECTIVES/GOALS: Over 30% of patients with rheumatoid arthritis (RA) exhibit fibromyalgianess, a symptom cluster associated with increased pain sensitivity. Up to half of RA patients use oral glucocorticoids (GCs) long-term despite their known, dose-dependent toxicity. We examined the association between fibromyalgianess and oral GC persistence in RA patients. METHODS/STUDY POPULATION: We used data from the Central Pain in Rheumatoid Arthritis (CPIRA) cohort to follow participants with active RA on oral prednisone who initiated a new disease-modifying anti-rheumatic drug. We measured fibromyalgianess using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key fibromyalgia features often superimposed upon RA. We stratified fibromyalgianess severity as follows: FSQ<8 low, 8-10 moderate, >10 high/very high. We defined GC persistence as GC use at 3 month followup visit. We assessed the association between baseline fibromyalgianess (exposure) and GC persistence at followup (outcome) using multiple logistic regression, adjusted for demographics, RA duration, serostatus, and inflammatory activity measured by swollen joint count and C reactive protein. RESULTS/ANTICIPATED RESULTS: Of 97 participants on prednisone at baseline, 65% were taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent GC use, compared to 84% with high or very high fibromyalgianess. After adjustment as outlined above, participants with high/very high baseline fibromyalgianess remained more likely to be on prednisone at follow-up, relative to those with low fibromyalgianess (OR 4.99 [95% CI 1.20 – 20.73]). DISCUSSION/SIGNIFICANCE: In this cohort of patients with active RA, high fibromyalgianess is associated with persistent GC use, independent of inflammatory activity. This finding suggests non-inflammatory pain related to fibromyalgianess may be misclassified as inflammatory pain related to RA disease activity.
Research among non-industrial societies suggests that body kinematics adopted during running vary between groups according to the cultural importance of running. Among groups in which running is common and an important part of cultural identity, runners tend to adopt what exercise scientists and coaches consider to be good technique for avoiding injury and maximising performance. In contrast, among groups in which running is not particularly culturally important, people tend to adopt suboptimal technique. This paper begins by describing key elements of good running technique, including landing with a forefoot or midfoot strike pattern and leg oriented roughly vertically. Next, we review evidence from non-industrial societies that cultural attitudes about running associate with variation in running techniques. Then, we present new data from Tsimane forager–horticulturalists in Bolivia. Our findings suggest that running is neither a common activity among the Tsimane nor is it considered an important part of cultural identity. We also demonstrate that when Tsimane do run, they tend to use suboptimal technique, specifically landing with a rearfoot strike pattern and leg protracted ahead of the knee (called overstriding). Finally, we discuss processes by which culture might influence variation in running techniques among non-industrial societies, including self-optimisation and social learning.
Quasi-periodic plasmoid formation at the tip of magnetic streamer structures is observed to occur in experiments on the Big Red Ball as well as in simulations of these experiments performed with the extended magnetohydrodynamics code, NIMROD. This plasmoid formation is found to occur on a characteristic time scale dependent on pressure gradients and magnetic curvature in both experiment and simulation. Single mode, or laminar, plasmoids exist when the pressure gradient is modest, but give way to turbulent plasmoid ejection when the system drive is higher, which produces plasmoids of many sizes. However, a critical pressure gradient is also observed, below which plasmoids are never formed. A simple heuristic model of this plasmoid formation process is presented and suggested to be a consequence of a dynamic loss of equilibrium in the high-$\beta$ region of the helmet streamer. This model is capable of explaining the periodicity of plasmoids observed in the experiment and simulations, and produces plasmoid periods of 90 minutes when applied to two-dimensional models of solar streamers with a height of $3R_\odot$. This is consistent with the location and frequency at which periodic plasma blobs have been observed to form by Large Angle and Spectrometric Coronograph and Sun Earth Connection Coronal and Heliospheric Investigation instruments.
Magnetic reconnection is explored on the Terrestrial Reconnection Experiment (TREX) for asymmetric inflow conditions and in a configuration where the absolute rate of reconnection is set by an external drive. Magnetic pileup enhances the upstream magnetic field of the high-density inflow, leading to an increased upstream Alfvén speed and helping to lower the normalized reconnection rate to values expected from theoretical consideration. In addition, a shock interface between the far upstream supersonic plasma inflow and the region of magnetic flux pileup is observed, important to the overall force balance of the system, thereby demonstrating the role of shock formation for configurations including a supersonically driven inflow. Despite the specialized geometry where a strong reconnection drive is applied from only one side of the reconnection layer, previous numerical and theoretical results remain robust and are shown to accurately predict the normalized rate of reconnection for the range of system sizes considered. This experimental rate of reconnection is dependent on system size, reaching values as high as 0.8 at the smallest normalized system size applied.
Cancer in childhood is rare. The most recent SEER Cancer Statistics Review, released in April 2018 and covering 2011–2015, shows that for ages 0–14 the incidence of all cancer sites was 16.4 per 100,000 children, with mortality 2.1 per 100,000. Five-year relative survival for the same age group was 83.8% for years 2008–2014 [1]. (Rates from the European Cancer Information System are similar but are currently available only to 2012.) As of 2015, 1 in 750 of the adult population of the United States was a long-term survivor of childhood cancer [1, 2]. Cancer is more common after puberty, with incidence rising from 12.9 for ages 5–9 to 23.3 for ages 15–19 in the United States for years 2011–2015 [1], and many of these patients will be cured by combination treatment, with surgery, chemotherapy, and radiotherapy. Long-term survivors are nevertheless at risk of developing a number of late sequelae [3], including impaired fertility, adverse pregnancy outcomes, and health problems in offspring [4–6].
Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Methods
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Results
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Conclusions
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.
Aims
We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.
Method
SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.
Results
Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50).
Conclusions
In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
Analyses of embedded liberalism have focused overwhelmingly on trade in goods and capital, to the exclusion of migration. We argue that much as capital controls were essential components of the embedded liberal compromise, so too were restrictions on the democratic and social rights of labor migrants. Generous welfare programs in labor-receiving countries thrived alongside inclusionary immigration policies, but this balanced arrangement was only tenable if migrants were politically excluded in their destination countries. That is, embedded liberalism abroad rested on exclusionary political foundations at home. In bringing together the IPE literature on the “globalization trilemma” with the comparative politics of citizenship, we provide a novel account of how embedded liberalism worked politically, with implications for current debates about the fate of the liberal order in a time of populist resurgence.
The comparative effectiveness of antidepressant medication and cognitive-behaviour therapy for the acute treatment of depression is contentious.
Objective:
To compare the acute outcomes of antidepressant medication, cognitive-behaviour therapy (CBT), and the combination of the two, in adult, depressed patients.
Methods:
Sixteen electronic databases together with reference lists were searched for randomised and other clinical trials that compared CBT, antidepressants, or their combination.
Results:
In the comparison between CBT and antidepressants, 8 studies met inclusion criteria. Five studies met the inclusion criteria for the second comparison between single therapy and combination therapy. In the antidepressant and CBT comparison, effect sizes favoured CBT over antidepressants with a significant advantage for CBT on some outcome measures. Combined treatment appeared more effective than antidepressants. However, combined treatment did not emerge more effective than CBT.
Conclusions:
Antidepressants may not be considered more efficacious than CBT for the acute treatment of depressed patients nor can combination therapy be regarded as more effective than CBT alone.
Gender representation is a pervasive problem in political science. We draw on evidence from the 2017 and 2018 American Political Science Association (APSA) Annual Meeting programs to discuss diversity and representation in large political science disciplinary conferences. APSA program divisions differ substantially in their gender representation: although some are representative of their organized-section membership, others are not, and some sections are particularly likely to feature “manels.” We present representation data by organized section, with discussions of what representation looks like and identifying different types of representation goals. We conclude by offering guidelines for increasing gender representation, for both future submitters and program chairs.
Functional gastrointestinal disorders including constipation affect up to 14 % of the world's population. Treatment is difficult and challenging resulting in a need for alternative safe and effective therapies. The present study investigated whether daily consumption of three gold-fleshed kiwifruit could alleviate constipation and improve gastrointestinal discomfort in mildly constipated individuals with and without pain. A total of thirty-two participants were enrolled in a 16-week randomised, single-blind, crossover study. Participants received either three ‘Zesy002’ kiwifruit or 14·75 g Metamucil® (5 g dietary fibre/d (a positive control)) for 4 weeks each with a 4-week washout between treatments. A 2-week washout period was included at the beginning and end of the study. Daily bowel habit diaries were kept throughout the study. The primary outcome measure was differences in the number of complete spontaneous bowel movements (CSBM). Secondary outcome measures were bowel movement frequency and stool form as well as digestive symptoms and comfort. The number of CSBM per week was significantly greater during daily consumption of three kiwifruit compared with the baseline (6·3 v. 3·3; P < 0·05) and the Metamucil® treatment (6·3 v. 4·5; P < 0·05). Stool consistency was also improved, with kiwifruit producing softer stools and less straining (P < 0·05). Gastrointestinal discomfort was also improved compared with baseline for abdominal pain, constipation and indigestion (P < 0·05) during the kiwifruit intervention and constipation during the Metamucil® intervention (P < 0·05). This randomised controlled trial demonstrates that daily consumption of three gold-fleshed kiwifruit is associated with a significant increase of two CSBM per week and reduction in gastrointestinal discomfort in mildly constipated adults.