Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge.

A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex.

Identification of structural connections between neurons is a prerequisite to understanding brain function. Here we developed a pipeline to systematically map brain-wide monosynaptic input connections to genetically defined neuronal populations using an optimized rabies tracing system. We used mouse visual cortex as the exemplar system and revealed quantitative target-specific, layer-specific and cell-class-specific differences in its presynaptic connectomes.

Local connectivity and synaptic dynamics in mouse and human neocortex.

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap.

Human neocortical expansion involves glutamatergic neuron diversification.

The neocortex is disproportionately expanded in human compared with mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues.

Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells.

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties.

Impact of the Make Healthy Normal mass media campaign (Phase 1) on knowledge, attitudes and behaviours: a cohort study.

Objective: To determine the impact of the first phase of the Make Healthy Normal mass media campaign on NSW adults' active living and healthy eating knowledge, attitudes, intentions and behaviour.

Methods: Cohort design with NSW adults, followed up three times over 12 months, with n=939 participants completing all three waves. We used generalised linear mixed models to examine campaign awareness, knowledge, attitudes, intentions and behaviours over time.

The impact of a community-led program promoting weight loss and healthy living in Aboriginal communities: the New South Wales Knockout Health Challenge.

Background: Aboriginal people in Australia experience significant health burden from chronic disease. There has been limited research to identify effective healthy lifestyle programs to address risk factors for chronic disease among Aboriginal people.

Methods: The Knockout Health Challenge is a community-led healthy lifestyle program for Aboriginal communities across New South Wales, Australia.

The reach and flow of health information in two Aboriginal communities: a social network analysis.

The aim of the present paper was to explore how social networks enable dissemination of health information within two Aboriginal communities in New South Wales. The study design was modelled on a social network analysis socio-centric model. Data collection was conducted primarily by Aboriginal community members who were trained as community researchers.

Pragmatic cluster randomised trial of a free telephone-based health coaching program to support women in managing weight gain during pregnancy: the Get Healthy in Pregnancy Trial.

Background: Excessive gestational weight gain can result in poor maternal and child health outcomes. Estimates from single studies indicate the prevalence of excessive gestational weight gain in Australia could lie between 38 and 67 %. The risk of excessive weight gain can be reduced through healthy eating and exercise.

Weight-Related Goal Setting in a Telephone-Based Preventive Health-Coaching Program: Demonstration of Effectiveness.

Purpose: This study investigated whether participants in a 6-month telephone-based coaching program, who set physical activity, nutrition, and weight loss goals had better outcomes in these domains.

Design: Quasi-experimental design.

Setting: The Australian Get Healthy Information and Coaching Service (GHS), a free population-wide telephone health-coaching service that includes goal setting as a key component of its coaching program.

PET imaging studies show enhanced expression of mGluR5 and inflammatory response during progressive degeneration in ALS mouse model expressing SOD1-G93A gene.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disorder. Genetic studies have linked mutation of the gene SOD1 to ALS pathology as well as several other pathological processes including modulation of glutamatergic function and inflammatory processes. Since therapeutic approaches for ALS are focused on glutamatergic function, we investigated modulation of glutamate transport based on its receptor function as well as excitotoxicity-induced inflammatory response.

The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia.

Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia.

A pre-and-post study of an urban renewal program in a socially disadvantaged neighbourhood in Sydney, Australia.

Background: Urban renewal programs aim to target both the physical and social environments to improve the social capital, social connectedness, sense of community and economic conditions of residents of the neighbourhoods. We evaluated the impact of an urban renewal program on the health and well-being of residents of a socially disadvantaged community in south-western Sydney, Australia.

Methods: Pre- and post-urban renewal program surveys were conducted with householders by trained interviewers.

Building capacity for evidence-based practice in the health promotion workforce: evaluation of a train-the-trainer initiative in NSW.

Issue Addressed: Evidence-based practice (EBP) is essential for effective health promotion practice, but not all health promotion staff have the required skills. In New South Wales this issue was addressed by implementing an EBP train-the-trainer (TTT) program to build workforce capacity.

Methods: The success of the program was assessed through surveys completed by EBP-TTT participants and AHS participants of the disseminated EBP training activities.

A health impact assessment on the construction phase of a major hospital redevelopment.

A prospective health impact assessment (HIA) was conducted to identify potential health impacts arising from the planned redevelopment of Liverpool Hospital, a major teaching hospital in New South Wales, Australia. A multidisciplinary team of health professionals oversaw the HIA and a core project team led by population health practitioners conducted the HIA using a structured, stepwise process. Methods used to gather data for the identification of impacts were a literature review, development of a population profile and consultation with stakeholders.

Ontology-based interactive information extraction from scientific abstracts.

Over recent years, there has been a growing interest in extracting information automatically or semi-automatically from the scientific literature. This paper describes a novel ontology-based interactive information extraction (OBIIE) framework and a specific OBIIE system. We describe how this system enables life scientists to make ad hoc queries similar to using a standard search engine, but where the results are obtained in a database format similar to a pre-programmed information extraction engine.

A health impact assessment of the Liverpool Hospital redevelopment.

This case study describes the process and results of a prospective health impact assessment that was conducted on a major hospital redevelopment in NSW. Undertaking the health impact assessment has raised awareness of the potential intended and unintended consequences of redevelopment in relation to health. It has also enhanced the capacity and commitment for health impact assessment within the Area Health Service.

Promoting evidence-based practice in population health at the local level: a case study in workforce capacity development.

This paper describes a service-based initiative to enhance capacity for evidence-based practice (EBP) in the South Western Sydney Area Health Service Division of Population Health. A working group planned an organisational response to a customised EBP needs assessment using the New South Wales Department of Health's framework for capacity building focussing on five key action areas; organisational development, workforce development, resource allocation, leadership and partnerships. Innovative strategies to promote EBP were developed and implemented and on-site training programs that targeted specific groups of staff were conducted.