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Recent changes in US government priorities have serious negative implications for science that will compromise the integrity of mental health research, which focuses on vulnerable populations. Therefore, as editors of mental science journals and custodians of the academic record, we confirm with conviction our collective commitment to communicating the truth.
Metabolic dietary patterns, including the Empirical Dietary Index for Hyperinsulinaemia (EDIH) and Empirical Dietary Inflammatory Pattern (EDIP), are known to impact multiple chronic diseases, but the role of the colonic microbiome in mediating such relationships is poorly understood. Among 1,610 adults with faecal 16S rRNA data in the TwinsUK cohort, we identified the microbiome profiles for EDIH and EDIP (from food frequency questionnaires) cross-sectionally using elastic net regression. We assessed the association of the dietary pattern-related microbiome profile scores with circulating biomarkers in multivariable-adjusted linear regression. In addition, we used PICRUSt2 to predict biological pathways associated with the enriched microbiome profiles, and further screened pathways for associations with the dietary scores in linear regression analyses. Microbiome profile scores developed with 32 (EDIH) and 15 (EDIP) genera were associated with higher insulin and homeostatic model assessment of insulin resistance. Six genera were associated with both dietary scores: Ruminococcaceae_UCG-008, Lachnospiraceae_UCG-008, Defluviitaleaceae_UCG-011 Anaeroplasma, inversely and Negativibacillus, Streptococcus, positively. Further, pathways in fatty acid biosynthesis, sugar acid degradation, and mevalonate metabolism were associated with insulinaemic and inflammatory diets. Dietary patterns that exert metabolic effects on insulin and inflammation may influence chronic disease risk by modulating gut microbial composition and function.
Climate variability is expected to increase due to climate change, with projected increases in temperature and erratic rainfall patterns. These changes will alter the environmental cues sensed by seeds, and therefore will impact plant recruitment. This study investigated the effects of seed functional traits (germinability, germination time, synchrony and seed mass) on germination responses of several sub-tropical native Australian plant species under different environmental factors (water stress, salinity and pH). The effect of a hot water pre-treatment was also tested on Fabaceae seeds with known physical dormancy. Seed traits, environmental factors and seed pre-treatments had significant effects on final germination percentage and germination time. Seed mass and time to 50% germination (t50) were also positively correlated. In contrast, pH did not affect germination and there was no interaction between pH and any of the measured seed functional traits. Some species showed a high thermal tolerance to germination and germination was indifferent to light conditions for all species. Results showed that certain seed functional traits interact with environmental factors to influence germination percentage and time. These findings highlight the importance of considering seed functional traits when determining a species germination response under a changing climate. In addition, the findings provide important knowledge to better guide seed-based land restoration programmes.
Establishing causal relationships in observational studies is an important step in research and policy decision making. The association between an exposure and an outcome can be confounded by multiple factors, often making it hard to draw causal conclusions. The co-twin control design (CTCD) is a powerful approach that allows for the investigation of causal effects while controlling for genetic and shared environmental confounding factors. This article introduces the CTCD and offers an overview of analysis methods for binary and continuous outcome and exposure variables. Tools for data simulation are provided, along with practical guidance and accompanying scripts for implementing the CTCD in R, SPSS, and Stata. While the CTCD offers valuable insights into causal inference, it depends on several assumptions that are important when interpreting CTCD results. By presenting a broad overview of the CTCD, this article aims to equip researchers with actionable recommendations and a comprehensive understanding of the design’s strengths and limitations.
The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms.
Methods
We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5.
Results
Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations.
Conclusions
The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations.
System-level change is crucial for solving society's most pressing problems. However, individual-level interventions may be useful for creating behavioral change before system-level change is in place and for increasing necessary public support for system-level solutions. Participating in individual-level solutions may increase support for system-level solutions – especially if the individual-level solutions are internalized as part of one's social identity.
This article describes a novel approach to the control of a powered knee prosthesis where the control system provides passive behavior for most activities and then provides powered assistance only for those activities that require them. The control approach presented here is based on the categorization of knee joint function during activities into four behaviors: resistive stance behavior, active stance behavior, ballistic swing, and non-ballistic swing. The approach is further premised on the assumption that healthy non-perturbed swing-phase is characterized by a ballistic swing motion, and therefore, a replacement of that function should be similarly ballistic. The control system utilizes a six-state finite-state machine, where each state provides different constitutive behaviors (concomitant with the four aforementioned knee behaviors) which are appropriate for a range of activities. Transitions between states and torque control within states is controlled by user motion, such that the control system provides, to the extent possible, knee torque behavior as a reaction to user motion, including for powered behaviors. The control system is demonstrated on a novel device that provides a sufficiently low impedance to enable a strictly passive ballistic swing-phase, while also providing sufficiently high torque to offer powered stance-phase knee-extension during activities such as step-over stair ascent. Experiments employing the knee and control system on an individual with transfemoral amputation are presented that compare the functionality of the power-supplemented nominally passive system with that of a conventional passive microprocessor-controlled knee prosthesis.
Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.
Methods
Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).
Results
Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.
Conclusions
The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.
Funding
Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.
To characterize the features of aged care users who died by suicide and examine the use of mental health services and psychopharmacotherapy in the year before death.
Design:
Population-based, retrospective exploratory study
Setting and participants:
Individuals who died while accessing or waiting for permanent residential aged care (PRAC) or home care packages in Australia between 2008 and 2017.
Measurements:
Linked datasets describing aged care use, date and cause of death, health care use, medication use, and state-based hospital data collections.
Results:
Of 532,507 people who died, 354 (0.07%) died by suicide, including 81 receiving a home care package (0.17% of all home care package deaths), 129 in PRAC (0.03% of all deaths in PRAC), and 144 approved for but awaiting care (0.23% of all deaths while awaiting care). Factors associated with death by suicide compared to death by another cause were male sex, having a mental health condition, not having dementia, less frailty, and a hospitalization for self-injury in the year before death. Among those who were awaiting care, being born outside Australia, living alone, and not having a carer were associated with death by suicide. Those who died by suicide more often accessed Government-subsidized mental health services in the year before their death than those who died by another cause.
Conclusions:
Older men, those with diagnosed mental health conditions, those living alone and without an informal carer, and those hospitalized for self-injury are key targets for suicide prevention efforts.
High-quality evidence from prospective longitudinal studies in humans is essential to testing hypotheses related to the developmental origins of health and disease. In this paper, the authors draw upon their own experiences leading birth cohorts with longitudinal follow-up into adulthood to describe specific challenges and lessons learned. Challenges are substantial and grow over time. Long-term funding is essential for study operations and critical to retaining study staff, who develop relationships with participants and hold important institutional knowledge and technical skill sets. To maintain contact, we recommend that cohorts apply multiple strategies for tracking and obtain as much high-quality contact information as possible before the child’s 18th birthday. To maximize engagement, we suggest that cohorts offer flexibility in visit timing, length, location, frequency, and type. Data collection may entail multiple modalities, even at a single collection timepoint, including measures that are self-reported, research-measured, and administrative with a mix of remote and in-person collection. Many topics highly relevant for adolescent and young adult health and well-being are considered to be private in nature, and their assessment requires sensitivity. To motivate ongoing participation, cohorts must work to understand participant barriers and motivators, share scientific findings, and provide appropriate compensation for participation. It is essential for cohorts to strive for broad representation including individuals from higher risk populations, not only among the participants but also the staff. Successful longitudinal follow-up of a study population ultimately requires flexibility, adaptability, appropriate incentives, and opportunities for feedback from participants.
Within the past few years, the study of Latin American politics has been increasingly influenced by a theoretical perspective that the outcome of World War II temporarily relegated to the “dustbin of history.” This perspective is the corporate one, long associated with the political perversions of Hitler's Germany, Mussolini's Italy, and a handful of postwar continental regimes such as Spain and Portugal which were considered by most observers to be political backwaters.
Threat avoidance is a prominent symptom of affective disorders, yet its biological basis remains poorly understood. Here, we used a validated task, the Joystick Operated Runway Task (JORT), combined with fMRI, to explore whether abnormal function in neural circuits responsible for avoidance underlies these symptoms. Eighteen individuals with major depressive disorder (MDD) and 17 unaffected controls underwent the task, which involved using physical effort to avoid threatening stimuli, paired with mild electric shocks on certain trials. Activity during anticipation and avoidance of threats was explored and compared between groups. Anticipation of aversive stimuli was associated with significant activation in the dorsal anterior cingulate cortex, superior frontal gyrus, and striatum, while active avoidance of aversive stimuli was associated with activity in dorsal anterior cingulate cortex, insula, and prefrontal cortex. There were no significant group differences in neural activity or behavioral performance on the JORT; however, participants with depression reported more dread while being chased on the task. The JORT effectively identified neural systems involved in avoidance and anticipation of aversive stimuli. However, the absence of significant differences in behavioral performance and activation between depressed and non-depressed groups suggests that MDD is not associated with abnormal function in these networks. Future research should investigate the basis of passive avoidance in major depression. Further, the JORT should be explored in patients with anxiety disorders, where threat avoidance may be a more prominent characteristic of the disorder.
This paper introduces a method to improve the design procedure of axiomatic design theory (AD) with Extenics. A comprehensive review of the AD indicates that the powerful principle of AD has been widely studied and applied to many areas, however, inexperienced practitioners of the AD theory still find it difficult to follow or apply the principles in their design which inadvertently often leads to misunderstanding and skepticism. The lack of definitive descriptions for all the elements and specific approaches to guiding the mapping process restricts the development and application of AD theory. This paper improves the design procedure of AD with Extenics. The elements in AD domain are expressed by basic-elements of Extenics, and the formulations are generated. The mapping process based on AD and Extenics is developed. The improved design procedure provides designers with a theoretical foundation based on the logical and rational thought process, meanwhile the solution space can be expanded and innovative designs are inspired. Based on the proposed design procedure, a computer-aided system is developed, which makes the complex and fuzzy design activity clear and easy to follow by filling in the blanks in a step-by-step manner. An example of a novel corn harvester header design scheme is considered to illustrate the validity of the improved design procedure.
Waves 1 to 3 (March 2020 to May 2020) of the UK COVID-19 Mental Health and Wellbeing study suggested an improvement in some indicators of mental health across the first 6 weeks of the UK lockdown; however, suicidal ideation increased.
Aims
To report the prevalence of mental health and well-being of adults in the UK from March/April 2020 to February 2021.
Method
Quota sampling was employed at wave 1 (March/April 2020), and online surveys were conducted at seven time points. Primary analyses cover waves 4 (May/June 2020), 5 (July/August 2020), 6 (October 2020) and 7 (February 2021), including a period of increased restrictions in the UK. Mental health indicators were suicidal ideation, self-harm, suicide attempt, depression, anxiety, defeat, entrapment, loneliness and well-being.
Results
A total of 2691 (87.5% of wave 1) individuals participated in at least one survey between waves 4 and 7. Depressive symptoms and loneliness increased from October 2020 to February 2021. Defeat and entrapment increased from July/August 2020 to October 2020, and remained elevated in February 2021. Well-being decreased from July/August 2020 to October 2020. Anxiety symptoms and suicidal ideation did not change. Young adults, women, those who were socially disadvantaged and those with a pre-existing mental health condition reported worse mental health.
Conclusions
The mental health and well-being of the UK population deteriorated from July/August 2020 to October 2020 and February 2021, which coincided with the second wave of COVID-19. Suicidal thoughts did not decrease significantly, suggesting a need for continued vigilance as we recover from the pandemic.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
Methods
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
Results
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Conclusions
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
The aim of this review is to explore how metabolic changes induced by diets high in saturated fat (HFD) affect nucleus accumbens (NAc) dopamine neurotransmission and food intake, and to explore how stress and inflammation influence this process. Recent evidence linked diet-induced obesity and HFD with reduced dopamine release and reuptake. Altered dopamine neurotransmission could disrupt satiety circuits between NAc dopamine terminals and projections to the hypothalamus. The NAc directs learning and motivated behaviours based on homeostatic needs and psychological states. Therefore, impaired dopaminergic responses to palatable food could contribute to weight gain by disrupting responses to food cues or stress, which impacts type and quantity of food consumed. Specifically, saturated fat promotes neuronal resistance to anorectic hormones and activation of immune cells that release proinflammatory cytokines. Insulin has been shown to regulate dopamine neurotransmission by enhancing satiety, but less is known about effects of diet-induced stress. Therefore, changes to dopamine signalling due to HFD warrant further examination to characterise crosstalk of cytokines with endocrine and neurotransmitter signals. A HFD promotes a proinflammatory environment that may disrupt neuronal endocrine function and dopamine signalling that could be exacerbated by the hypothalamic–pituitary–adrenal and κ-opioid receptor stress systems. Together, these adaptive changes may dysregulate eating by changing NAc dopamine during hedonic versus homeostatic food intake. This could drive palatable food cravings during energy restriction and hinder weight loss. Understanding links between HFD and dopamine neurotransmission will inform treatment strategies for diet-induced obesity and identify molecular candidates for targeted therapeutics.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.