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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Adolescence is a key developmental period associated with an increased risk of experiencing cannabis-related problems. Identifying modifiable risk factors prior to the onset of cannabis use could help inform preventative interventions.
Method
Analysis nested within a UK prospective birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants (n = 6,049) provided data on cannabis use and symptoms of cannabis problems using the Cannabis Abuse Screening Test at two or more time points between the ages of 15–24 years. Risk factors included internalizing and externalizing disorders assessed at age 10 years, and cognitive function assessed at age 8 years via short-term memory, emotion recognition, divided attention, and listening comprehension.
Results
Participants were mostly female (59.1%) and white (95.73%). Five patterns of adolescent cannabis use problems were identified using longitudinal latent class analysis: stable-no problems (n = 5,157, 85%), early-onset high (n = 104, 2%), late-onset high (n = 153, 3%), early onset low (n = 348, 6%), and late-onset low (n = 287, 5%). In adjusted models, externalizing disorders were associated with early-onset high [RR, 95% CI: 2.82 (1.72, 4.63)], late-onset high [RR, 95% CI: 1.62 (1.02, 2.57)], and early-onset low [RR, 95% CI: 1.82 (1.30, 2.55)] compared to the stable-no problems class. Internalizing disorders were associated with late-onset low only [RR, 95% CI: .50 (.26, .96)], and short-term memory with late-onset high only [RR, 95% CI: 1.09 (1.01, 1.18) compared to the stable-no problems class.
Conclusions
Childhood externalizing disorders were consistently associated with increased risk of problematic patterns of cannabis use over adolescence, particularly early-onset and high levels of problems.
Observational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding.
Methods
A systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle–Ottawa Scale, confounder matrix, E-values, and Doi plots.
Results
Seventy-five studies were included. Tobacco use was associated with mood disorders (K = 43; RR: 1.39, 95% confidence interval [CI] 1.30–1.47), but not anxiety disorders (K = 7; RR: 1.21, 95% CI 0.87–1.68) and evidence for psychotic disorders was influenced by treatment of outliers (K = 4, RR: 3.45, 95% CI 2.63–4.53; K = 5, RR: 2.06, 95% CI 0.98–4.29). Cannabis use was associated with psychotic disorders (K = 4; RR: 3.19, 95% CI 2.07–4.90), but not mood (K = 7; RR: 1.31, 95% CI 0.92–1.86) or anxiety disorders (K = 7; RR: 1.10, 95% CI 0.99–1.22). Confounder matrices and E-values suggested potential overestimation of effects. Only 27% of studies were rated as high quality.
Conclusions
Both substances were associated with psychotic disorders and tobacco use was associated with mood disorders. There was no clear evidence of an association between cannabis use and mood or anxiety disorders. Limited high-quality studies underscore the need for future research using robust causal inference approaches (e.g. evidence triangulation).
Preoperative nasopharyngeal viral screening may reduce clinical uncertainty of upper respiratory infections prior to pediatric cardiac surgery but with unclear benefit. From March 2018 to March 2020, patients aged <3 years were screened for respiratory viruses and had substantial rates of viral detection (40%) but no observed differences in outcomes.
To assess the impact of a diagnostic test stewardship intervention focused on tracheal aspirate cultures.
Design:
Quality improvement intervention.
Setting:
Tertiary care pediatric intensive care unit (PICU).
Patients:
Mechanically ventilated children admitted between 9/2018 and 8/2022.
Methods:
We developed and implemented a consensus guideline for obtaining tracheal aspirate cultures through a series of Plan-Do-Study-Act cycles. Change in culture rates and broad-spectrum antibiotic days of therapy (DOT) per 100 ventilator days were analyzed using statistical process control charts. A secondary analysis comparing the preintervention baseline (9/2018–8/2020) to the postintervention period (9/2020–8/2021) was performed using Poisson regression.
Results:
The monthly tracheal aspirate culture rate prior to the COVID-19 pandemic (9/2018–3/2020) was 4.6 per 100 ventilator days. A centerline shift to 3.1 cultures per 100 ventilator days occurred in 4/2020, followed by a second shift to 2.0 cultures per 100 ventilator days in 12/2020 after guideline implementation. In our secondary analysis, the monthly tracheal aspirate culture rate decreased from 4.3 cultures preintervention (9/2018–8/2020) to 2.3 cultures per 100 ventilator days postintervention (9/2020–8/2021) (IRR 0.52, 95% CI 0.47–0.59, P < 0.01). Decreases in tracheal aspirate culture use were driven by decreases in inappropriate cultures. Treatment of ventilator-associated infections decreased from 1.0 to 0.7 antibiotic courses per 100 ventilator days (P = 0.03). There was no increase in mortality, length of stay, readmissions, or ventilator-associated pneumonia postintervention.
Conclusion:
A diagnostic test stewardship intervention was both safe and effective in reducing the rate of tracheal aspirate cultures and treatment of ventilator-associated infections in a tertiary PICU.
Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.
Relative to their typically developing peers, autistic individuals experience greater difficulties in domains of functioning that are relevant to learning and adult outcomes, such as sensory sensitivities, anxiety, and social. However, little is known about how difficulties in these domains relate to the receipt of special education services as well as adult outcomes, such as vocational achievement. The current study sought to fill this gap by examining if difficulties in various learning-related domains as ascertained via the Learning Needs Screening Tool (LNST) were associated with historical special education receipt and vocational status.
Participants and Methods:
400 autistic adults, recruited via the Simons Powering Autism Research (SPARK) participant registry Research Match service, participated in this study (40.5% male, mean age=28.9 years). All participants completed the LNST, which collects responses to 13 core questions about learning (such as challenges with memorization, note taking, spelling and identifying arithmetic signs), as well as 7 additional questions with checkbox and free response options, and yields a total score from 0-30. LNST item 14 and its response options (1-9) capture suspected causes of learning difficulties (e.g., 'too much noise or activity bothers me,' 'I get nervous taking tests'). These individual questions as well as the total of endorsed learning related challenges were then evaluated in relation to historical special education receipt (“yes” vs. “no”) and vocational outcomes (“yes” vs. “no” engaging in 10+ hours of postsecondary education or employment without supports), as assessed via the Taylor Vocational Index.
Results:
Logistic regression was utilized to predict the dependent variables of interest. Models included sex assigned at birth and age in the first step as covariates. Then either the total of learning related challenges endorsed or the 9 individual learning-related challenges from the LNST were included as independent variables of interest. For historical special education receipt, two items - “It’s hard for me to work by myself” (B = .78, p<.05) and “I get nervous taking tests” (B = .49, p<.05) were positively associated with a history of special education services. For vocational outcomes, the total learning related challenges (B = -.25, p<.001) as well as endorsement of one item -“It’s hard for me to work by myself” (B = -.88, p=<.05) were associated with poorer vocational outcomes.
Conclusions:
These findings shed light on the possible learning-related challenges that are experienced by autistic adults. Further examination of the role these learning related challenges play in the receipt of special education and on vocational outcomes is warranted. In particular, difficulties with independence in work was related to both special education receipt and poorer vocational outcomes, indicating that it may be a fruitful area of focus for vocational training programs.
Large research teams and consortia present challenges for authorship. The number of disciplines involved in the research can further complicate approaches to manuscript development and leadership. The CHARM team, representing a multi-disciplinary, multi-institutional genomics implementation study, participated in facilitated discussions inspired by team science methodologies. The discussions were centered on team members’ past experiences with authorship and perspectives on authorship in a large research team context. Team members identified challenges and opportunities that were used to create guidelines and administrative tools to support manuscript development. The guidelines were organized by the three values of equity, inclusion, and efficiency and included eight principles. A visual dashboard was created to allow all team members to see who was leading or involved in each paper. Additional tools to promote equity, inclusion, and efficiency included providing standardized project management for each manuscript and making “concept sheets” for each manuscript accessible to all team members. The process used in CHARM can be used by other large research teams and consortia to equitably distribute lead authorship opportunities, foster coauthor inclusion, and efficiently work with large authorship groups.
Laterality of paired organs involves the function of the eyes, ears, hands and feet. Whilst most people have a right-handed preference, about 10 per cent are left-handed. Similarly, the right eye is usually preferred to the left. Medicine is both taught and practised for those with right hand and eye preference, and left-handed medical students and doctors must negotiate the right-handed world.
Objective
This brief review looks at society's attitudes, medical training and the practice of otolaryngology in the UK towards laterality and handedness.
Method
Literature review.
Results
Studies suggest that left-handers are more versatile and so are more ambidextrous. Conversely, this may result in problems when a right-hander tries to undertake a procedure with the non-dominant hand.
Conclusion
Cultures and attitudes are changing towards those who are left-handed. Left-handed surgeons may encounter difficulties in the clinical environment throughout their training.
Our study aimed to explore how perceived baseline contact may influence acceptability of Connecting Today, a personal contact intervention, among people living with dementia. We aimed to generate hypotheses for testing in future studies. This was a sub-group analysis of pilot study data. Fifteen people living with mild to moderate dementia participated in Connecting Today. We explored how perceptions of intervention acceptability may differ in groups reporting weekly contact (n = 8) compared with groups reporting monthly/unknown (n = 7) contact at baseline. Measures of acceptability included a treatment perceptions and preferences questionnaire, and the number of and reasons for non-consent, missing data, and study withdrawal. We used descriptive statistics and content analysis. In visits one and two, a larger proportion (85.7–100%) of low baseline contact participants reported feeling better, and indicated that the visits helped them and were easy “mostly” or “a lot”, compared with the high baseline contact group (37.5–62.5%). Most missing data (71%) and all study withdrawals occurred in the high baseline contact group. Scheduled in-person visits with family, friends, or a volunteer may appeal to residents in care homes who have few existing opportunities for routine, one-on-one visits with others. Hypotheses generated should be tested in future studies.
To conduct a process evaluation of a respiratory culture diagnostic stewardship intervention.
Design:
Mixed-methods study.
Setting:
Tertiary-care pediatric intensive care unit (PICU).
Participants:
Critical care, infectious diseases, and pulmonary attending physicians and fellows; PICU nurse practitioners and hospitalist physicians; pediatric residents; and PICU nurses and respiratory therapists.
Methods:
This mixed-methods study was conducted concurrently with a diagnostic stewardship intervention to reduce the inappropriate collection of respiratory cultures in mechanically ventilated children. We quantified baseline respiratory culture utilization and indications for ordering using quantitative methods. Semistructured interviews informed by these data and the Consolidated Framework for Implementation Research (CFIR) were then performed, recorded, transcribed, and coded to identify salient themes. Finally, themes identified in these interviews were used to create a cross-sectional survey.
Results:
The number of cultures collected per day of service varied between attending physicians (range, 2.2–27 cultures per 100 days). In total, 14 interviews were performed, and 87 clinicians completed the survey (response rate, 47%) and 77 nurses or respiratory therapists completed the survey (response rate, 17%). Clinicians varied in their stated practices regarding culture ordering, and these differences both clustered by specialty and were associated with perceived utility of the respiratory culture. Furthermore, group “default” practices, fear, and hierarchy were drivers of culture orders. Barriers to standardization included fear of a missed diagnosis and tension between practice standardization and individual decision making.
Conclusions:
We identified significant variation in utilization and perceptions of respiratory cultures as well as several key barriers to implementation of this diagnostic test stewardship intervention.
To determine the association between delay in transfer to a central stroke unit from peripheral institutions and outcomes.
Methods:
We conducted a retrospective cohort study of all patients with acute stroke, admitted to a comprehensive stroke center (CSC) from three emergency departments (EDs), between 2016 and 2018. The primary outcomes were length of stay, functional status at 3 months, discharge destination, and time to stroke investigations.
Results:
One thousand four hundred thirty-five patients were included, with a mean age of 72.9 years, and 92.4% ischemic stroke; 663 (46.2%) patients were female. Each additional day of delay was associated with 2.0 days of increase in length of stay (95% confidence interval [CI] 0.8–3.2, p = 0.001), 11.5 h of delay to vascular imaging (95% CI 9.6–13.4, p < 0.0001), 24.2 h of delay to Holter monitoring (95% CI 7.9–40.6, p = 0.004), and reduced odds of nondisabled functional status at 3 months (odds ratio 0.98, 95% CI 0.96–1.00, p = 0.01). Factors affecting delay included stroke onset within 6 h of ED arrival (605.9 min decrease in delay, 95% CI 407.9–803.9, p < 0.0001), delay to brain imaging (59.4 min increase in delay for each additional hour, 95% CI 48.0–71.4, p < 0.0001), admission from an alternative service (3918.7 min increase in delay, 95% CI 3621.2–4079.9, p < 0.0001), and transfer from a primary stroke center (PSC; 740.2 min increase in delay, 95% CI 456.2–1019.9, p < 0.0001).
Conclusion:
Delay to stroke unit admission in a system involving transfer from PSCs to a CSC was associated with longer hospital stay and poorer functional outcomes.
Background: Tracheal aspirate bacterial cultures are routinely collected in mechanically ventilated children for the evaluation of ventilator-associated infections (VAIs). However, frequent bacterial colonization of endotracheal and tracheostomy tubes contribute to the marginal performance characteristics of the test for diagnosing VAI. Published literature characterizing drivers of culture collection and the predictive value of positive cultures are limited. Methods: This single-center, retrospective cohort study included children admitted to the pediatric intensive care unit who were receiving mechanical ventilation for at least 48 hours and had 1 or more semiquantitative tracheal aspirate cultures collected between September 1, 2019, and August 31, 2020. Indications for culture collection were determined through medical record review and included fever, hypothermia, tracheal secretion changes, radiographic pneumonia, increased oxygen requirement, and/or increased positive end-expiratory pressure (PEEP). A positive culture was defined as moderate or heavy growth of a noncommensal bacterial organism. A purulent Gram stain was defined as detection of moderate or many white blood cells. Diagnosis of VAI was based on treating-clinician documentation and was ascertained through medical record review. Logistic regression accounting for clustering by patient was performed to estimate the association between indications for culture collection and (1) culture positivity, (2) purulent Gram stain, and (3) diagnosis of VAI. Results: In total, 625 tracheal aspirate cultures were performed in 261 unique patients. Common indications for culture collection included isolated fever or hypothermia (n = 124, 20%), fever with an increase in oxygen requirement or PEEP (n = 71, 11%), isolated increase in oxygen requirement or PEEP (n = 67, 11%), or isolated secretion change (n = 54, 9%) (Figure 1). Overall, 230 cultures (37%) were positive and 218 (35%) Gram stains were purulent. There were no associations between culture indications and a positive culture. Presence of isolated fever was negatively associated with a purulent Gram stain (odds ratio [OR], 0.49; 95% CI, 0.30–0.81; P = .005); otherwise, there were no associations between indication and purulent Gram stain. Finally, in a multivariable model, odds of VAI diagnosis increased with both the number of indications for culture collection and purulent Gram stain, but not with positive culture (Figure 2). Conclusions: Number and type of clinical signs were not associated with tracheal aspirate culture positivity or purulence on Gram stain, but they were associated with a clinical diagnosis of VAI. These findings suggest that positive tracheal aspirate cultures may not aid clinicians in the diagnosis of VAI, and they highlight the opportunity for improved diagnostic stewardship.
Mass shootings account for a small fraction of annual worldwide murders, yet disproportionately affect society and influence policy. Evidence suggesting a link between mass shootings and severe mental illness (i.e. involving psychosis) is often misrepresented, generating stigma. Thus, the actual prevalence constitutes a key public health concern.
Methods
We examined global personal-cause mass murders from 1900 to 2019, amassed by review of 14 785 murders publicly described in English in print or online, and collected information regarding perpetrator, demographics, legal history, drug use and alcohol misuse, and history of symptoms of psychiatric or neurologic illness using standardized methods. We distinguished whether firearms were or were not used, and, if so, the type (non-automatic v. semi- or fully-automatic).
Results
We identified 1315 mass murders, 65% of which involved firearms. Lifetime psychotic symptoms were noted among 11% of perpetrators, consistent with previous reports, including 18% of mass murderers who did not use firearms and 8% of those who did (χ2 = 28.0, p < 0.01). US-based mass shooters were more likely to have legal histories, use recreational drugs or misuse alcohol, or have histories of non-psychotic psychiatric or neurologic symptoms. US-based mass shooters with symptoms of any psychiatric or neurologic illness more frequently used semi-or fully-automatic firearms.
Conclusions
These results suggest that policies aimed at preventing mass shootings by focusing on serious mental illness, characterized by psychotic symptoms, may have limited impact. Policies such as those targeting firearm access, recreational drug use and alcohol misuse, legal history, and non-psychotic psychopathology might yield more substantial results.
The aim of this review is to present the current options for cardiac output (CO) monitoring in children undergoing cardiac surgery. Current technologies for monitoring identified were a range of invasive, minimally invasive, and non-invasive technologies. These include pulmonary artery catheter, transoesophageal echocardiography, pulse contour analysis, electrical cardiography, and thoracic bioreactance. A literature search was conducted using evidence databases which identified two current guidelines; the NHS Greater Glasgow and Clyde guideline and Royal College of Anaesthetics Guideline. These were appraised using the AGREE II tool and the evidence identified was used to create an overview summary of each technological option for CO monitoring. There is limited evidence regarding the accuracy of modalities available for CO monitoring in paediatric patients during cardiac surgery. Each technology has advantages and disadvantages; however, none could be championed as the most beneficial. Furthermore, a gold standard for CO monitoring has not yet been identified for paediatric populations, nor is it apparent whether one modality is preferable based on the available evidence. Additional evidence using a standardised method for comparing CO measurements should be conducted in order to determine the best option for CO monitoring in paediatrics. Furthermore, cost-effectiveness assessment of each modality should be conducted. Only then will it be possible for clear, evidence-based guidance to be written.
OBJECTIVES/GOALS: Diverse medication-based studies require longitudinal drug dose information. EHRs can provide such data, but multiple mentions of a drug in the same clinical note can yield conflicting dose. We aimed to develop statistical methods which address this challenge by predicting the valid dose in the event that conflicting doses are extracted. METHODS/STUDY POPULATION: We extracted dose information for two test drugs, tacrolimus and lamotrigine, from Vanderbilt EHRs using a natural language processing system, medExtractR, which was developed by our team. A random forest classifier was used to estimate the probability of correctness for each extracted dose on the basis of subject longitudinal dosing patterns and extracted EHR note context. Using this feasibility measure and other features such as a summary of subject dosing history, we developed several statistical models to predict the dose on the basis of the extracted doses. The models developed based on supervised methods included a separate random forest regression, a transition model, and a boosting model. We also considered unsupervised methods and developed a Bayesian hierarchical model. RESULTS/ANTICIPATED RESULTS: We compared model-predicted doses to physician-validated doses to evaluate model performance. A random forest regression model outperformed all proposed models. As this model is a supervised model, its utility would depend on availability of validated dose. Our preliminary result from a Bayesian hierarchical model showed that it can be a promising alternative although performing less optimally. The Bayesian hierarchical model would be especially useful when validated dose data are not available, as it was developed in unsupervised modeling framework and hence does not require validated dose that can be difficult and time consuming to obtain. We evaluated the feasibility of each method for automatic implementation in our drug dosing extraction and processing system we have been developing. DISCUSSION/SIGNIFICANCE OF IMPACT: We will incorporate the developed methods as a part of our complete medication extraction system, which will allow to automatically prepare large longitudinal medication dose datasets for researchers. Availability of such data will enable diverse medication-based studies with drastically reduced barriers to data collection.
Dietary fibre is believed to provide important health benefits including protection from colorectal cancer. However, the evidence on the relationships with different dietary fibre sources is mixed and little is known about which fibre source provides the greatest benefits. We conducted a dose–response meta-analysis of prospective cohorts to summarise the relationships of different fibre sources with colorectal cancer and adenoma risks. Analyses were restricted to publications that reported all fibre sources (cereals, vegetables, fruits, legumes) to increase comparability between results. PubMed and Embase were searched through August 2018 to identify relevant studies. The summary relative risks (RR) and 95 % CI were estimated using a random-effects model. This analysis included a total of ten prospective studies. The summary RR of colorectal cancer associated with each 10 g/d increase in fibre intake were 0·91 (95 % CI 0·82, 1·00; I2 = 0 %) for cereal fibre, 0·95 (95 % CI 0·87, 1·03, I2 = 0 %) for vegetable fibre, 0·91 (95 % CI 0·78, 1·06, I2 = 43 %) for fruit fibre and 0·84 (95 % CI 0·63, 1·13, I2 = 45 %) for legume fibre. For cereal fibre, the association with colorectal cancer risk remained statistically significant after adjustment for folate intake (RR 0·89, 95 % CI 0·80, 0·99, I2 = 2 %). For vegetable and fruit fibres, the dose–response curve suggested evidence of non-linearity. All fibre sources were inversely associated with incident adenoma (per 10 g/d increase: RR 0·81 (95 % CI 0·54, 1·21) cereals, 0·84 (95 % CI 0·71, 0·98) for vegetables, 0·78 (95 % CI 0·65, 0·93) for fruits) but not associated with recurrent adenoma. Our data suggest that, although all fibre sources may provide some benefits, the evidence for colorectal cancer prevention is strongest for fibre from cereals/grains.
The democratisation of design permits greater stakeholder involvement in what has traditionally been a domain reserved for experts; the design process itself. This is enabled by technological advances in fields such as 3D printing, virtual reality and high-speed peer to peer communication technologies which have fuelled the development of new and innovative design methods. This paper compares and contrasts different approaches to the democratisation of design, and in particular, those that aim to involve wider stakeholders in the design process itself. Three different approaches(design by play, design by generation and crowdsourcing for design) are defined and contextualised within existing design frameworks and their respective suitabilities to democratise different design phases are considered. An exemplar use case of each approach is presented in order to assess how stakeholder engagement is affected by each democratising strategy. The discussion compares and contrasts the approaches with respect to their applicability and utility for different stages of the design process and how the power dynamics of the design process are altered when the different approaches are employed.
Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.