Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.

Where's the Marker? Perceptions of Whiteboards in the Emergency Department.

BACKGROUND: In the emergency department, bedside whiteboards are used to help improve communication, teamwork, and collaboration among health care providers. In addition, previous studies have shown that whiteboards aid the patient with the identification of their health care providers, plan of care, expected length of stay, and overall patient satisfaction. PURPOSE: This evidence-based evaluation project assessed the perceptions of emergency department health care providers on their awareness of the effectiveness of bedside whiteboards, whether there are challenges with using them, and whether they are being updated and used consistently. METHOD: A survey was utilized to evaluate emergency department health care providers (nurses, patient care technicians, and attending providers) on their perceptions of bedside whiteboards in the patient rooms using a 10-question survey. OUTCOMES: The survey was sent via email to 135 emergency department health care providers, with 64 respondents. The survey results showed that 41.3% of the respondents agreed that bedside whiteboards promote patient satisfaction, 36.5% agreed that they promote patient safety, 53.1% agreed they take minimal completion time, and 50% felt they help keep patients informed about care. However, 85.9% of participants felt bedside whiteboards are not updated consistently, and 81.2% felt they are not updated consistently among all 3 shifts. In addition, 73.4% reported that they lack access to materials to update the whiteboards and 38.1% were neutral regarding whiteboards promoting patient safety. IMPLICATIONS: Proper materials (markers and erasers) are integral to bedside whiteboard use. Continued staff education on the function of bedside whiteboards may improve proper whiteboard use.

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression.

BACKGROUND: Despite cognitive behavioral therapy (CBT) being a standard treatment in major depressive disorder (MDD), nearly half of patients do not respond. As one of the predictors of CBT's efficacy is amygdala reactivity to positive information, which is often decreased in MDD, we explored whether real-time fMRI neurofeedback (rtfMRI-nf) training to increase amygdala responses during positive memory recall prior CBT would enhance its efficacy. METHODS: In a double-blind, placebo controlled, randomized clinical trial, 35 adults with MDD received two sessions of rtfMRI-nf training to increase their amygdala (experimental group, n = 16) or parietal (control group, n = 19) responses during positive memory neurofeedback prior to receiving 10 CBT sessions. Depressive symptomatology was monitored between the rtfMRI sessions, the first three, 9th and 10th sessions of CBT and at 6 months and 1 year follow-up. RESULTS: Participants in the experimental group showed decreased depressive symptomatology and higher remission rates at 6 months and 1 year follow-up than the control group. Analysis of CBT content highlighted that participants in the experimental group focused more on positive thinking and behaviors than the control group. LIMITATIONS: The study was relatively small and not sufficiently powered to detect small effects. CONCLUSIONS: CBT, when combined with amygdala neurofeedback, results in sustained clinical changes and leads to long-lasting clinical improvement, potentially by increasing focus on positive memories and cognitions.

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

The effect of external flow on the feeding currents of sessile microorganisms.

Microscopic sessile suspension feeders live attached to surfaces and, by consuming bacteria-sized prey and by being consumed, they form an important part of aquatic ecosystems. Their environmental impact is mediated by their feeding rate, which depends on a self-generated feeding current. The feeding rate has been hypothesized to be limited by recirculating eddies that cause the organisms to feed from water that is depleted of food particles. However, those results considered organisms in still water, while ambient flow is often present in their natural habitats. We show, using a point-force model, that even very slow ambient flow, with speed several orders of magnitude less than that of the self-generated feeding current, is sufficient to disrupt the eddies around perpendicular suspension feeders, providing a constant supply of food-rich water. However, the feeding rate decreases in external flow at a range of non-perpendicular orientations due to the formation of recirculation structures not seen in still water. We quantify the feeding flow and observe such recirculation experimentally for the suspension feeder Vorticella convallaria in external flows typical of streams and rivers.

"Stop talking around projects and talk about solutions": Positioning health within infrastructure policy to achieve the sustainable development goals.

PURPOSE AND SETTING: Infrastructure is a global multi-trillion dollar market presenting many opportunities and risks for sustainable development. This article aims to foster better conceptualisation of the connections and tensions between infrastructure policy and public health in the light of the Sustainable Development Goals, especially 'good health and wellbeing' (number 3) and 'industry, innovation and infrastructure' (number 9), based on findings from interviews with a purposive sample of senior practicing Australian infrastructure policy makers. PRINCIPAL FINDINGS: We use an institutional framework to explore the ideas, actors, rules and mandates, and procedures underpinning the inclusion of health in infrastructure policy. Informants defined infrastructure as the construction and provision of services that facilitate economic, environmental and social outcomes. The tendency to default to infrastructure as essential for economic success has fundamental challenges for the SDGs, particularly the politically driven pursuit of 'mega-project' legacies, sector-specific siloed governance arrangements, and inadequate conceptualisations of costs and benefits. CONCLUSIONS: Public health and infrastructure policy are mutually re-enforcing given they both concern the public interest with implications for all 17 SDGs. Positioning health and wellbeing as fundamental societal outcomes from infrastructure decisions would go a long way to helping achieve the SDGs.

Including health impacts in environmental impact assessments for three Australian coal-mining projects: a documentary analysis.

Notwithstanding the historical benefits of coal in aiding human and economic development, the negative health and environmental impacts of coal extraction and processing are of increasing concern. Environmental impact assessments (EIAs) are a regulated policy mechanism that can be used to predict and consider the health impacts of mining projects to determine if consent is given. The ways in which health is considered within EIA is unclear. This research investigated 'How and to what extent are health, well-being and equity issues considered in Environmental Impact Assessments (EIAs) of major coal mining projects in New South Wales, Australia'. To this end we developed and applied a comprehensive coding framework designed to interrogate the publicly available environmental impact statements (EISs) of three mines in New South Wales (NSW), Australia, for their inclusion of health, well-being and equity issues. Analysis of the three EISs demonstrates that: the possible impacts of each mine on health and well-being were narrowly and inadequately considered; when health and well-being were considered there was a failure to assess the possible impacts specific to the particular mine and the communities potentially affected; the cumulative impacts on human health of multiple mines in the same geographical area were almost completely ignored; the discussions of intragenerational and intergenerational equity did not demonstrate a sound understanding of equity and, it is essential that governments' requirements for the EIA include detailed analysis of the health, well-being, equity and cumulative impacts specific to the proposed mine and relevant communities.

Healthy urban planning: an institutional policy analysis of strategic planning in Sydney, Australia.

Rapid urbanization requires health promotion practitioners to understand and engage with strategic city planning. This policy analysis research investigated how and why health was taken up into strategic land use planning in Sydney, Australia, between 2013 and 2018. This qualitative study develops two case studies of consecutive instances of strategic planning in Sydney. Data collection was done via in-depth stakeholder interviews (n = 11) and documentary analysis. Data collection and analysis revolved around core categories underpinning policy institutions (actors, structures, ideas, governance and power) to develop an explanatory narrative of the progress of 'health' in policy discourse over the study period. The two strategic planning efforts shifted in policy discourse. In the earlier plan, 'healthy built environments' was positioned as a strategic direction, but without a mandate for action the emphasis was lost in an economic growth agenda. The second effort shifted that agenda to ecological sustainability, a core aspect of which was 'Liveability', having greater potential for health promotion. However, 'health' remained underdeveloped as a core driver for city planning remaining without an institutional mandate. Instead, infrastructure coordination was the defining strategic city problem and this paradigm defaulted to emphasizing 'health precincts' rather than positioning health as core for the city. This research demonstrates the utility in institutional analysis to understanding positioning health promotion in city planning. Despite potential shifts in policy discourse and a more sophisticated approach to planning holistically, the challenge remains of embedding health within the institutional mandates driving city planning.

Inclusion of Health in Environmental Impact Assessment of Major Transport Infrastructure Projects in Vietnam.

BACKGROUND: Infrastructure spending, especially in the transport sector, is expected to increase rapidly in Vietnam. This boost in transportation investment impacts health. Environmental impact assessments (EIAs) are essential tools for decision-making to reduce and mitigate anticipated impacts of development projects, and integration of health assessment as an essential part of the EIA process has been regulated in many high-income countries. There is, however, limited knowledge about how health is evaluated in these environmental assessments in low- and middle-income countries (LMICs) such as Vietnam. METHODS: We did an analysis of EIAs of four major transport projects in Vietnam, applying a six-step coding framework previously used to investigate EIAs in the Australian context. RESULTS: We found that health was inadequately considered in all four EIAs. There was no direct health assessment within the four EIAs due to the lack of formal requirements from either Government or the financing agency, the Asian Development Bank (ADB). Health issues were often identified as risks posed by the projects within the assessment of impacts on environmental conditions. A broader consideration of health was limited. When social outcomes of the projects were present in EIAs, they were often mentioned once without any detailed assessment or linking to health. There was no evidence linking health benefits and shifts towards active travel with the construction of two metro rail projects. Mitigation measures offered in all four EIAs were found to be generic and insubstantial. CONCLUSION: The health assessments in the EIAs of four transport projects in Vietnam were significantly less detailed than those in Australia, mainly due to the lack of legislative requirements. The lack of health content indicates the need for involvement of health experts in the environmental assessment process, as well as requirements for the health assessment to be integrated in EIA. Our findings suggest there is the need to build capacity both within and outside of government to fully consider the health impacts of infrastructure in EIA practice.

Swimming of peritrichous bacteria is enabled by an elastohydrodynamic instability.

Peritrichously-flagellated bacteria, such as Escherichia coli, self-propel in fluids by using specialised motors to rotate multiple helical filaments. The rotation of each motor is transmitted to a short flexible segment called the hook which in turn transmits it to a flagellar filament, enabling swimming of the whole cell. Since multiple motors are spatially distributed on the body of the organism, one would expect the propulsive forces from the filaments to push against each other leading to negligible swimming. We use a combination of computations and theory to show that the swimming of peritrichous bacteria is enabled by an elastohydrodynamic bending instability occurring for hooks more flexible than a critical threshold. Using past measurements of hook bending stiffness, we demonstrate how real bacteria are safely on the side of the instability that promotes systematic swimming.

Addressing Health Equity Through Action on the Social Determinants of Health: A Global Review of Policy Outcome Evaluation Methods.

BACKGROUND: Epidemiological evidence on the social determinants of health inequity is well-advanced, but considerably less attention has been given to evaluating the impact of public policies addressing those social determinants. Methodological challenges to produce evidence on policy outcomes present a significant barrier to mobilising policy actions for health equities. This review aims to examine methodological approaches to policy evaluation of health equity outcomes and identify promising approaches for future research. METHODS: We conducted a systematic narrative review of literature critically evaluating policy impact on health equity, synthesizing information on the methodological approaches used. We searched and screened records from five electronic databases, using pre-defined protocols resulting in a total of 50 studies included for review. We coded the studies according to (1) type of policy analysed; (2) research design; (3) analytical techniques; (4) health outcomes; and (5) equity dimensions evaluated. RESULTS: We found a growing number of a wide range of policies being evaluated for health equity outcomes using a variety of research designs. The majority of studies employed an observational research design, most of which were cross-sectional, however, other approaches included experimental designs, simulation modelling, and meta-analysis. Regression techniques dominated the analytical approaches, although a number of novel techniques were used which may offer advantages over traditional regression analysis for the study of distributional impacts of policy. Few studies made intra-national or cross-national comparisons or collected primary data. Despite longstanding challenges of attribution in policy outcome evaluation, the majority of the studies attributed change in physical or mental health outcomes to the policy being evaluated. CONCLUSION: Our review provides an overview of methodological approaches to health equity policy outcome evaluation, demonstrating what is most commonplace and opportunities from novel approaches. We found the number of studies evaluating the impacts of public policies on health equity are on the rise, but this area of policy evaluation still requires more attention given growing inequities.

Including Health in Environmental Assessments of Major Transport Infrastructure Projects: A Documentary Analysis.

BACKGROUND: Transport policy and practice impacts health. Environmental Impact Assessments (EIAs) are regulated public policy mechanisms that can be used to consider the health impacts of major transport projects before they are approved. The way health is considered in these environmental assessments (EAs) is not well known. This research asked: How and to what extent was human health considered in EAs of four major transport projects in Australia. METHODS: We developed a comprehensive coding framework to analyse the Environmental Impact Statements (EISs) of four transport infrastructure projects: three road and one light rail. The coding framework was designed to capture how health was directly and indirectly included. RESULTS: We found that health was partially considered in all four EISs. In the three New South Wales (NSW) projects, but not the one South Australian project, this was influenced by the requirements issued to proponents by the government which directed the content of the EIS. Health was assessed using human health risk assessment (HHRA). We found this to be narrow in focus and revealed a need for a broader social determinants of health approach, using multiple methods. The road assessments emphasised air quality and noise risks, concluding these were minimal or predicted to improve. The South Australian project was the only road project not to include health data explicitly. The light rail EIS considered the health benefits of the project whereas the others focused on risk. Only one project considered mental health, although in less detail than air quality or noise. CONCLUSION: Our findings suggest EIAs lag behind the known evidence linking transport infrastructure to health. If health is to be comprehensively included, a more complete model of health is required, as well as a shift away from health risk assessment as the main method used. This needs to be mandatory for all significant developments. We also found that considering health only at the EIA stage may be a significant limitation, and there is a need for health issues to be considered when earlier, fundamental decisions about the project are being made.

A multiyear assessment of a hospital-school program to promote teen motor vehicle safety.

BACKGROUND: Motor vehicle crashes are the leading cause of death among teen drivers. The main goal of this program was to reduce texting while driving among high school teens through a unique peer-generated anti-texting campaign. METHODS: The program consisted of two phases. In phase 1, student leaders participated in a half-day, hospital-based experiential program that emphasized safe teen driving. In phase 2, these students conceptualized and implemented an anti-texting while driving campaign during the school year. The program enrolled 32 schools with 137 student participants in phase 1. This study uses a prospective quasi-experimental pre-post design. A presurvey and a follow-up online survey were used. Response rate was 81%. In phase 2, two rounds of observations of drivers were made near the participating schools at the beginning and end of the phase 2 campaign. The results were analyzed using proportion tests. RESULTS: There was a strong belief (6.49 on a seven-point scale) that texting while driving could result in a crash. About 58% had texted while driving in the previous 7 days in the pre-survey. This proportion decreased significantly to 44% in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing laws and feeling of empowerment to take action with a teen driver who was texting improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens) were observed in the first round, and 13,153 were observed in the second round of observations. Significant reduction in the proportion of drivers texting while driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver observations support the effectiveness of this program in meeting the key objective of reducing texting while driving. The program also influenced teenagers' willingness to take positive steps when faced with a driver who was texting. Future efforts should aim to influence social and peer norms. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Empirical resistive-force theory for slender biological filaments in shear-thinning fluids.

Many cells exploit the bending or rotation of flagellar filaments in order to self-propel in viscous fluids. While appropriate theoretical modeling is available to capture flagella locomotion in simple, Newtonian fluids, formidable computations are required to address theoretically their locomotion in complex, nonlinear fluids, e.g., mucus. Based on experimental measurements for the motion of rigid rods in non-Newtonian fluids and on the classical Carreau fluid model, we propose empirical extensions of the classical Newtonian resistive-force theory to model the waving of slender filaments in non-Newtonian fluids. By assuming the flow near the flagellum to be locally Newtonian, we propose a self-consistent way to estimate the typical shear rate in the fluid, which we then use to construct correction factors to the Newtonian local drag coefficients. The resulting non-Newtonian resistive-force theory, while empirical, is consistent with the Newtonian limit, and with the experiments. We then use our models to address waving locomotion in non-Newtonian fluids and show that the resulting swimming speeds are systematically lowered, a result which we are able to capture asymptotically and to interpret physically. An application of the models to recent experimental results on the locomotion of Caenorhabditis elegans in polymeric solutions shows reasonable agreement and thus captures the main physics of swimming in shear-thinning fluids.

A multiyear assessment of a hospital-school program to promote teen motor vehicle safety.

BACKGROUND: Motor vehicle crashes are the leading cause of death among teen drivers. The main goal of this program was to reduce texting while driving among high school teens through a unique peer-generated anti-texting campaign. METHODS: The program consisted of two phases. In phase 1, student leaders participated in a half-day, hospital-based experiential program that emphasized safe teen driving. In phase 2, these students conceptualized and implemented an anti-texting while driving campaign during the school year. The program enrolled 32 schools with 137 student participants in phase 1.This study uses a prospective quasi-experimental pre-post design. A presurvey and a follow-up online survey were used. Response rate was 81%. In phase 2, two rounds of observations of drivers were made near the participating schools at the beginning and end of the phase 2 campaign. The results were analyzed using proportion tests. RESULTS: There was a strong belief (6.49 on a seven-point scale) that texting while driving could result in a crash. About 58% had texted while driving in the previous 7 days in the pre-survey. This proportion decreased significantly to 44% in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing laws and feeling of empowerment to take action with a teen driver who was texting improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens) were observed in the first round, and 13,153 were observed in the second round of observations. Significant reduction in the proportion of drivers texting while driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver observations support the effectiveness of this program in meeting the key objective of reducing texting while driving. The program also influenced teenagers' willingness to take positive steps when faced with a driver who was texting. Future efforts should aim to influence social and peer norms. LEVEL OF EVIDENCE: Therapeutic study, level III.

Small-amplitude swimmers can self-propel faster in viscoelastic fluids.

Many small organisms self-propel in viscous fluids using travelling wave-like deformations of their bodies or appendages. Examples include small nematodes moving through soil using whole-body undulations or spermatozoa swimming through mucus using flagellar waves. When self-propulsion occurs in a non-Newtonian fluid, one fundamental question is whether locomotion will occur faster or slower than in a Newtonian environment. Here we consider the general problem of swimming using small-amplitude periodic waves in a viscoelastic fluid described by the classical Oldroyd-B constitutive relationship. Using Taylor's swimming sheet model, we show that if all travelling waves move in the same direction, the locomotion speed of the organism is systematically decreased. However, if we allow waves to travel in two opposite directions, we show that this can lead to enhancement of the swimming speed, which is physically interpreted as due to asymmetric viscoelastic damping of waves with different frequencies. A change of the swimming direction is also possible. By analysing in detail the cases of swimming using two or three travelling waves, we demonstrate that swimming can be enhanced in a viscoelastic fluid for all Deborah numbers below a critical value or, for three waves or more, only for a finite, non-zero range of Deborah numbers, in which case a finite amount of elasticity in the fluid is required to increase the swimming speed.

Adsorption at liquid interfaces induces amyloid fibril bending and ring formation.

Protein fibril accumulation at interfaces is an important step in many physiological processes and neurodegenerative diseases as well as in designing materials. Here we show, using ß-lactoglobulin fibrils as a model, that semiflexible fibrils exposed to a surface do not possess the Gaussian distribution of curvatures characteristic for wormlike chains, but instead exhibit a spontaneous curvature, which can even lead to ring-like conformations. The long-lived presence of such rings is confirmed by atomic force microscopy, cryogenic scanning electron microscopy, and passive probe particle tracking at air- and oil-water interfaces. We reason that this spontaneous curvature is governed by structural characteristics on the molecular level and is to be expected when a chiral and polar fibril is placed in an inhomogeneous environment such as an interface. By testing ß-lactoglobulin fibrils with varying average thicknesses, we conclude that fibril thickness plays a determining role in the propensity to form rings.

Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.

The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development, we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype.