Rigbox: An Open-Source Toolbox for Probing Neurons and Behavior.

Setting up an experiment in behavioral neuroscience is a complex process that is often managed with ad hoc solutions. To streamline this process, we developed Rigbox, a high-performance, open-source software toolbox that facilitates a modular approach to designing experiments (https://github.com/cortex-lab/Rigbox). Rigbox simplifies hardware input-output, time aligns datastreams from multiple sources, communicates with remote databases, and implements visual and auditory stimuli presentation. Its main submodule, Signals, allows intuitive programming of behavioral tasks. Here we illustrate its function with the following two interactive examples: a human psychophysics experiment, and the game of Pong. We give an overview of running experiments in Rigbox, provide benchmarks, and conclude with a discussion on the extensibility of the software and comparisons with similar toolboxes. Rigbox runs in MATLAB, with Java components to handle network communication, and a C library to boost performance.

Cortical State Fluctuations across Layers of V1 during Visual Spatial Perception.

Many factors modulate the state of cortical activity, but the importance of cortical state variability for sensory perception remains debated. We trained mice to detect spatially localized visual stimuli and simultaneously measured local field potentials and excitatory and inhibitory neuron populations across layers of primary visual cortex (V1). Cortical states with low spontaneous firing and correlations in excitatory neurons, and suppression of 3- to 7-Hz oscillations in layer 4, accurately predicted single-trial visual detection. Our results show that cortical states exert strong effects at the initial stage of cortical processing in V1 and can play a prominent role for visual spatial behavior in mice.

High-Yield Methods for Accurate Two-Alternative Visual Psychophysics in Head-Fixed Mice.

Research in neuroscience increasingly relies on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here, we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, facilitating repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires mice to use their visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopamine neurons. This stimulation elicits a larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis.

Integrated Clinical Decision Support Systems Promote Absolute Cardiovascular Risk Assessment: An Important Primary Prevention Measure in Aboriginal and Torres Strait Islander Primary Health Care.

BACKGROUND: Aboriginal and Torres Strait Islander Australians experience a greater burden of disease compared to non-Indigenous Australians. Around one-fifth of the health disparity is caused by cardiovascular disease (CVD). Despite the importance of absolute cardiovascular risk assessment (CVRA) as a screening and early intervention tool, few studies have reported its use within the Australian Indigenous primary health care (PHC) sector. This study utilizes data from a large-scale quality improvement program to examine variation in documented CVRA as a primary prevention strategy for individuals without prior CVD across four Australian jurisdictions. We also examine the proportion with elevated risk and follow-up actions recorded. METHODS: We undertook cross-sectional analysis of 2,052 client records from 97 PHC centers to assess CVRA in Indigenous adults aged ≥20 years with no recorded chronic disease diagnosis (2012-2014). Multilevel regression was used to quantify the variation in CVRA attributable to health center and client level factors. The main outcome measure was the proportion of eligible adults who had CVRA recorded. Secondary outcomes were the proportion of clients with elevated risk that had follow-up actions recorded. RESULTS: Approximately 23% (n = 478) of eligible clients had documented CVRA. Almost all assessments (99%) were conducted in the Northern Territory. Within this jurisdiction, there was wide variation between centers in the proportion of clients with documented CVRA (median 38%; range 0-86%). Regression analysis showed health center factors accounted for 48% of the variation. Centers with integrated clinical decision support systems were more likely to document CVRA (OR 21.1; 95% CI 5.4-82.4; p < 0.001). Eleven percent (n = 53) of clients were found with moderate/high CVD risk, of whom almost one-third were under 35 years (n = 16). Documentation of follow-up varied with respect to the targeted risk factor. Fewer than 30% with abnormal blood lipid or glucose levels had follow-up management plans recorded. CONCLUSION: There was wide variation in CVRA between jurisdictions and between PHC centers. Learnings from successful interventions to educate and support centers in CVRA provision should be shared with stakeholders more widely. Where risk has been identified, further improvement in follow-up management is required to prevent CVD onset and reduce future burden in Australia's Indigenous population.

Improving preventive health care in Aboriginal and Torres Strait Islander primary care settings.

BACKGROUND: Like other colonised populations, Indigenous Australians experience poorer health outcomes than non-Indigenous Australians. Preventable chronic disease is the largest contributor to the health differential between Indigenous and non-Indigenous Australians, but recommended best-practice preventive care is not consistently provided to Indigenous Australians. Significant improvement in health care delivery could be achieved through identifying and minimising evidence-practice gaps. Our objective was to use clinical audit data to create a framework of the priority evidence-practice gaps, strategies to address them, and drivers to support these strategies in the delivery of recommended preventive care. METHODS: De-identified preventive health clinical audit data from 137 primary health care (PHC) centres in five jurisdictions were analysed (n = 17,108 audited records of well adults with no documented major chronic disease; 367 system assessments; 2005-2014), together with stakeholder survey data relating to interpretation of these data, using a mixed-methods approach (n = 152 responses collated in 2015-16). Stakeholders surveyed included clinicians, managers, policy officers, continuous quality improvement (CQI) facilitators and academics. Priority evidence-practice gaps and associated barriers, enablers and strategies to address the gaps were identified and reported back through two-stages of consultation. Further analysis and interpretation of these data were used to develop a framework of strategies and drivers for health service improvement. RESULTS: Stakeholder identified priorities were: following-up abnormal test results; completing cardiovascular risk assessments; timely recording of results; recording enquiries about living conditions, family relationships and substance use; providing support for clients identified with emotional wellbeing risk; enhancing systems to enable team function and continuity of care. Drivers identified for improving care in these areas included: strong Indigenous participation in the PHC service; appropriate team structure and function to support preventive care; meaningful use of data to support quality of care and CQI; and corporate support functions and structures. CONCLUSION: The framework should be useful for guiding development and implementation of barrier-driven, tailored interventions for primary health care service delivery and policy contexts, and for guiding further research. While specific strategies to improve the quality of preventive care need to be tailored to local context, these findings reinforce the requirement for multi-level action across the system. The framework and findings may be useful for similar purposes in other parts of the world, with appropriate attention to context in different locations.

Wide Variation in Absolute Cardiovascular Risk Assessment in Aboriginal and Torres Strait Islander People with Type 2 Diabetes.

BACKGROUND: Absolute cardiovascular risk assessment (CVRA) is based on the combined effects of multiple risk factors and can identify asymptomatic individuals at high risk of cardiovascular disease (CVD). Aboriginal and Torres Strait Islander people, the Indigenous people of Australia, are disproportionately affected by CVD and diabetes. Our study aimed to investigate variations in the use of absolute CVRA in patients with diabetes at Indigenous community healthcare centers and to identify patient and health center characteristics that may contribute to this variation. METHODS: Audits of clinical records of 1,728 patients with a known diagnosis of diabetes across 121 health centers in four Australian States/Territories [Northern Territory (NT), South Australia, Western Australia, and Queensland] over the period 2012-2014 were conducted as part of a large-scale continuous quality improvement program. Multilevel regression modeling was used to quantify variation in recording of CVRA attributable to health center and patient characteristics. RESULTS: The proportion of eligible patients with documented CVRA was 33% (n = 574/1,728). The majority (95%) of assessments were conducted in the NT. Multilevel regression analysis showed health center characteristics accounted for 70% of the variation in assessments in the NT. Government-operated health centers had 18.8 times the odds (95% CI 7.7-46.2) of recording CVRA delivery compared with other health centers. CONCLUSION: Health centers in the NT delivered the majority of absolute CVRA to Indigenous patients with diabetes in our study. Health systems factors that may have facilitated provision of CVRA in the NT include decision support tools and a reporting process for CVRA delivery. Implementation of similar systems in other jurisdictions may help improve CVRA delivery. Early identification and treatment of high risk individuals through wider use of CVRA may help reduce the burden of CVD in Indigenous Australians with diabetes.

Strengthening cardiovascular disease prevention in remote indigenous communities in Australia's Northern Territory.

BACKGROUND: In 2012 the Northern Territory Department of Health commenced the Chronic Conditions Management Model - strengthening cardiovascular disease prevention in remote Indigenous communities. Interventions included providing regular functional reporting and decision support to frontline primary health care teams. METHODS: Longitudinal (three monthly) clinical audits of cardiac prevention services were undertaken between 2012 and 2014. Our primary outcome was population coverage of cardiovascular risk assessment for Indigenous clients aged 20 years and older. Secondary outcomes for those identified at high risk were (i) assessment of modifiable cardiac risk factors, (ii) prescription of risk lowering medications, and (iii) the proportion of high risk clients achieving clinical targets for risk reduction. RESULTS: As of August 2014, 7266 clients have had their cardiovascular risk assessed, improving population coverage from 23% in mid June 2012 to 58.5%. For 2586 high risk clients, 1728 (67%) and 1416 (55%) were prescribed blood pressure and lipid lowering therapy and for those clinically re-assessed, 1366 (57%) and 989 (40%) were achieving clinical targets for risk reduction for blood pressure and lipids respectively. CONCLUSIONS: Functional reporting and decision support was associated with improvement in cardiovascular risk assessment coverage and a sustained proportion of high risk clients achieving clinical targets for cardiovascular risk reduction. Further intervention-based research is required to close the gap between identification of risk and risk reduction.

Controlling phase noise in oscillatory interference models of grid cell firing.

Oscillatory interference models account for the spatial firing properties of grid cells in terms of neuronal oscillators with frequencies modulated by the animal's movement velocity. The phase of such a "velocity-controlled oscillator" (VCO) relative to a baseline (theta-band) oscillation tracks displacement along a preferred direction. Input from multiple VCOs with appropriate preferred directions causes a grid cell's grid-like firing pattern. However, accumulating phase noise causes the firing pattern to drift and become corrupted. Here we show how multiple redundant VCOs can automatically compensate for phase noise. By entraining the baseline frequency to the mean VCO frequency, VCO phases remain consistent, ensuring a coherent grid pattern and reducing its spatial drift. We show how the spatial stability of grid firing depends on the variability in VCO phases, e.g., a phase SD of 3 ms per 125 ms cycle results in stable grids for 1 min. Finally, coupling N VCOs with similar preferred directions as a ring attractor, so that their relative phases remain constant, produces grid cells with consistently offset grids, and reduces VCO phase variability of the order square root of N. The results suggest a viable functional organization of the grid cell network, and highlight the benefit of integrating displacement along multiple redundant directions for the purpose of path integration.

Measles transmission by 'fly-in fly-out' workers in Australia.

OBJECTIVE: To describe the outbreak investigation and control measures for a cluster of measles cases involving 'fly-in fly-out' (FIFO) workers on an off-shore industrial vessel. METHODS: Following Australian guidelines, measles cases were interviewed and at-risk contacts on the Australian mainland received measles vaccine, immunoglobulin or health advice. For the industrial vessel: (i) exposed FIFO workers who had already left the vessel received health advice through their employer; (ii) workers remaining on the vessel were offered measles vaccine; and (iii) FIFO workers joining the vessel for 21 days following the prodrome onset of the last case of measles on the vessel were offered measles vaccine. Measles virus isolates were sent for genotype determination. RESULTS: Four measles cases from two Australian jurisdictions were epidemiologically linked to the retrospectively identified index case, a New Zealand FIFO worker. No further cases were detected following the institution of outbreak control measures. CONCLUSION: FIFO workers congregating on large industrial projects are a discrete risk group with the potential to spread infectious diseases over large distances, both domestically and internationally. IMPLICATIONS: FIFO workers' immunisation history should be reviewed prior to deployment. Catch-up vaccination, where appropriate, would minimise transmission of vaccine-preventable diseases such as measles and help maintain a healthy, productive workforce.

Early identification and preventive care for elevated cardiovascular disease risk within a remote Australian Aboriginal primary health care service.

BACKGROUND: Cardiovascular disease (CVD) is the single greatest contributor to the gap in life expectancy between Indigenous and non-Indigenous Australians. Our objective is to determine if holistic CVD risk assessment, introduced as part of the new Aboriginal and Torres Strait Islander Adult Health Check (AHC), results in better identification of elevated CVD risk, improved delivery of preventive care for CVD and improvements in the CVD risk profile for Aboriginal adults in a remote community. METHODS: Interrupted time series study over six years in a remote primary health care (PHC) service involving Aboriginal adults identified with elevated CVD risk (N = 64). Several process and outcome measures were audited at 6 monthly intervals for three years prior to the AHC (the intervention) and three years following: (i) the proportion of guideline scheduled CVD preventive care services delivered, (ii) mean CVD medications prescribed and dispensed, (iii) mean PHC consultations, (iv) changes in participants' CVD risk factors and estimated absolute CVD risk and (v) mean number of CVD events and iatrogenic events. RESULTS: Twenty-five percent of AHC participants were identified as having elevated CVD risk. Of these, 84% had not been previously identified during routine care. Following the intervention, there were significant improvements in the recorded delivery of preventive care services for CVD (30% to 53%), and prescription of CVD related medications (28% to 89%) (P < 0.001). Amongst participants there was a 20% relative reduction in estimated absolute CVD risk (P = 0.004) following the intervention. However, there were no significant changes in the mean number of PHC consultations or mean number of CVD events or iatrogenic events. CONCLUSIONS: Holistic CVD risk assessment during an AHC can lead to better and earlier identification of elevated CVD risk, improvement in the recorded delivery of preventive care services for CVD, intensification of treatment for CVD, and improvements in participants' CVD risk profile. Further research is required on strategies to reorient and restructure PHC services to the care of chronic illness for Aboriginal peoples in remote areas for there to be substantial progress in decreasing excess CVD related mortality.

Healthy country, healthy people: the relationship between Indigenous health status and "caring for country".

OBJECTIVE: To investigate associations between "caring for country" -- an activity that Indigenous peoples assert promotes good health -- and health outcomes relevant to excess Indigenous morbidity and mortality. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study involving 298 Indigenous adults aged 15-54 years in an Arnhem Land community, recruited from March to September 2005. MAIN OUTCOME MEASURES: Self-reported involvement in caring for country, health behaviours and clinically measured body mass index (BMI), waist circumference, blood pressure, type 2 diabetes status, albumin to creatinine ratio (ACR), levels of glycated haemoglobin (HbA(1c)) and high-density lipoprotein (HDL) cholesterol, lipid ratio, score on the five-item version of the Kessler Psychological Distress Scale (K5), and 5-year cardiovascular disease (CVD) risk. RESULTS: Controlling for sociodemographic characteristics and health behaviours, multivariate regression revealed significant and substantial associations between caring for country and health outcomes. An interquartile range rise in the weighted composite caring-for-country score was significantly associated with more frequent physical activity, better diet, lower BMI (regression coefficient [b] = - 2.83; 95% CI, - 4.56 to - 1.10), less abdominal obesity (odds ratio [OR], 0.43; 95% CI, 0.26-0.72), lower systolic blood pressure (b = - 7.59; 95% CI, - 12.01 to - 3.17), less diabetes (OR, 0.12; 95% CI, 0.03-0.52), lower HbA(1c) level (b = - 0.45; 95% CI, - 0.79 to - 0.11), non-elevated ACR (OR, 0.28; 95% CI, 0.13-0.60), higher HDL cholesterol level (b = 0.06; 95% CI, 0.01-0.12), lower K5 score (b = - 0.97; 95% CI, - 1.64 to - 0.31) and lower CVD risk (b = - 0.77; 95% CI, - 1.43 to - 0.11). CONCLUSIONS: Greater Indigenous participation in caring for country activities is associated with significantly better health. Although the causal direction of these associations requires clarification, our findings suggest that investment in caring for country may be a means to foster sustainable economic development and gains for both ecological and Indigenous peoples' health.

Development and preliminary validation of the 'Caring for Country' questionnaire: measurement of an Indigenous Australian health determinant.

BACKGROUND: 'Caring for Country' is defined as Indigenous participation in interrelated activities with the objective of promoting ecological and human health. Ecological services on Indigenous-owned lands are belatedly attracting some institutional investment. However, the health outcomes associated with Indigenous participation in 'caring for country' activities have never been investigated. The aims of this study were to pilot and validate a questionnaire measuring caring for country as an Indigenous health determinant and to relate it to an external reference, obesity. METHODS: Purposively sampled participants were 301 Indigenous adults aged 15 to 54 years, recruited during a cross-sectional program of preventive health checks in a remote Australian community. Questionnaire validation was undertaken with psychometric tests of internal consistency, reliability, exploratory factor analysis and confirmatory one-factor congeneric modelling. Accurate item weightings were derived from the model and used to create a single weighted composite score for caring for country. Multiple linear regression modelling was used to test associations between the caring for country score and body mass index adjusting for socio-demographic factors and health behaviours. RESULTS: The questionnaire demonstrated adequate internal consistency, test-retest validity and proxy-respondent validity. Exploratory factor analysis of the 'caring for country' items produced a single factor solution that was confirmed via one-factor congeneric modelling. A significant and substantial association between greater participation in caring for country activities and lower body mass index was demonstrated. Adjusting for socio-demographic factors and health behaviours, an inter-quartile range rise in caring for country scores was associated with 6.1 Kg and 5.3 Kg less body weight for non-pregnant women and men respectively. CONCLUSION: This study indicates preliminary support for the validity of the caring for country concept and a questionnaire designed to measure it. This study also highlights the importance of investigating Indigenous-asserted health promotion activities. Further studies in similar populations are merited to test the generalisability of this questionnaire and to explore associations with other important Indigenous health outcomes.