2015 Inaugural CURF annual forum 2014: connecting leading research and practice for a sustainable capital region

Held in November 2014, the Inaugural CURF Annual Forum brought over 100 participants representing government, industry, academia and the community from the ACT and the Australian Capital Region to the University of Canberra. The Forum was officially opened by the ACT Deputy Chief Minister Simon Corbell MLA and the University of Canberra\u27s Vice-Chancellor, Mr Stephen Parker AO.  CURF Director, Professor Barbara Norman, chaired the Forum. The Forum hosted four workshops. Participants were encouraged to identify both challenges and potential solutions in achieving a sustainable future. Those workshops were:  • Climate Adaptation for Canberra and the Region • Renewable Energy for Canberra and the Region • Integrated Transport for Canberra and the Region • Community Health and Wellbeing for Canberra and the Region The outcomes of these workshops, and a detailed recording of the Forum, is found in the 2014 Inaugural CURF Annual Forum Outcomes Paper.&nbsp

Special issue: Update on neural oscillations in neuropsychiatric disorders

The present issue highlights recent progress in the analysis of oscillatory activity for the assessment, understanding and remediation of psychiatric and neurologic disorders. Contemporary interest in neural synchrony and oscillations in neuropsychiatric disorders has been motivated by investigations of cellular and network oscillations, modeling of neural networks and advances in signal analysis. Hebb1 proposed that synchronous activation between two neurons strengthened connectivity between them; and that a reverberatory neural circuit could maintain a representation of a stimulus in memory. More recent findings implicate neural synchrony and oscillations in feature binding, attentional selection, arousal, memory operations and consciousness.2-9 Consequently, disturbances of oscillations within and between neural ensembles may contribute to sensory, behavioral and cognitive deficits in neuropsychiatric disorders. Because human EEG and MEG activity are generated by synchronized inhibitory and excitatory post-synaptic potentials within large ensembles of neurons, they are well suited for the detection of neural synchrony and oscillations with millisecond temporal resolution

Novel Cemented Technique for Trochanteric Fixation and Reconstruction of the Abductor Mechanism in Proximal and Total Femoral Arthroplasty: An Observational Study

Background: Little evidence exists regarding the clinical outcomes of cemented trochanteric fixation for abductor mechanism reconstruction in proximal or total femoral replacements. Clinical outcomes were assessed for a novel cemented technique for trochanteric fixation in femoral megaprostheses. Methods: A descriptive series of 13 patients who underwent proximal or total femoral arthroplasty from 2016 to 2019 were reviewed. Radiographic trochanteric displacement \u3e 1 cm defined construct failure. A Kaplan-Meier survival analysis was performed to determine survival rates for these cemented constructs. Demographic information was obtained to better characterize the patient population in whom this technique was used. Results: Eleven patients were included (age = 63.6 years; 45.4% females; body mass index = 31.7). Mean time to final radiographic follow-up was 73.8 weeks. Three of 11 (27.2%) patients had construct failure. Overall, survival at 1 year was 81.8%. At 2 years, survival of cemented constructs was 65.5%. More construct failures occurred in patients who sustained a postoperative dislocation than in those who did not (P = .05). Conclusions: This novel cemented trochanteric fixation technique for reconstruction of the abductor mechanism in femoral megaprostheses had 81.8% survival at 1 year postoperatively. While longitudinal comparative studies with larger samples are needed, the cemented technique may provide a viable alternative to traditional cementless methods of trochanteric fixation. Increased construct failure rates after postoperative dislocation highlight the importance of robust abductor reconstruction in these implants

Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening

N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS

The Depression Treatment Cascade in Primary Care: A Public Health Perspective

Major depressive disorder (MDD) is common and costly. Primary care remains a major access point for depression treatment, yet the successful clinical resolution of depression in primary care is uncommon. The clinical response to depression suffers from a “treatment cascade”: the affected individual must access health care, be recognized clinically, initiate treatment, receive adequate treatment, and respond to treatment. Major gaps currently exist in primary care at each step along this treatment continuum. We estimate that 12.5% of primary care patients have had MDD in the past year; of those with MDD, 47% are recognized clinically, 24% receive any treatment, 9% receive adequate treatment, and 6% achieve remission. Simulations suggest that only by targeting multiple steps along the depression treatment continuum (e.g. routine screening combined with collaborative care models to support initiation and maintenance of evidence-based depression treatment) can overall remission rates for primary care patients be substantially improved

Auditory feature perception and auditory hallucinatory experiences in schizophrenia spectrum disorder

Schizophrenia spectrum disorder (SZ) is associated with deficits in auditory perception as well as auditory verbal hallucinations (AVH). However, the relationship between auditory feature perception and auditory verbal hallucinations (AVH), one of the most commonly occurring symptoms in psychosis, has not been well characterized. This study evaluated perception of a broad range of auditory features in SZ and to determine whether current AVHs relate to auditory feature perception. Auditory perception, including frequency, intensity, duration, pulse-train and temporal order discrimination, as well as an embedded tone task, was assessed in both AVH (n = 20) and non-AVH (n = 24) SZ individuals and in healthy controls (n = 29) with the Test of Basic Auditory Capabilities (TBAC). The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) was used to assess the experience of auditory hallucinations in patients with SZ. Findings suggest that compared to controls, the SZ group had greater deficits on an array of auditory features, with non-AVH SZ individuals showing the most severe degree of abnormality. IQ and measures of cognitive processing were positively associated with performance on the TBAC for all SZ individuals, but not with the HPSVQ scores. These findings indicate that persons with SZ demonstrate impaired auditory perception for a broad range of features. It does not appear that impaired auditory perception is associated with recent auditory verbal hallucinations, but instead associated with the degree of intellectual impairment in SZ

Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia

Prominent conceptual models characterize schizophrenia as a dysconnectivity syndrome, with recent research focusing on the contributions of the cerebellum in this framework. The present study examined the role of the cerebellum and its effective connectivity to the cerebrum during sensorimotor synchronization in schizophrenia. Specifically, the role of the cerebellum in temporally coordinating cerebral motor activity was examined through path analysis. Thirty-one individuals diagnosed with schizophrenia and 40 healthy controls completed a finger-tapping fMRI task including tone-paced synchronization and self-paced continuation tapping at a 500 ms intertap interval (ITI). Behavioral data revealed shorter and more variable ITIs during self-paced continuation, greater clock (vs motor) variance, and greater force of tapping in the schizophrenia group. In a whole-brain analysis, groups showed robust activation of the cerebellum during self-paced continuation but not during tone-paced synchronization. However, effective connectivity analysis revealed decreased connectivity in individuals with schizophrenia between the cerebellum and primary motor cortex but increased connectivity between cerebellum and thalamus during self-paced continuation compared with healthy controls. These findings in schizophrenia indicate diminished temporal coordination of cerebral motor activity by cerebellum during the continuation tapping portion of sensorimotor synchronization. Taken together with the behavioral finding of greater temporal variability in schizophrenia, these effective connectivity results are consistent with structural and temporal models of dysconnectivity in the disorder

Mycobacterium tuberculosis antigen 85B and ESAT-6 expressed as a recombinant fusion protein in Mycobacterium smegmatis elicits cell-mediated immune response in a murine vaccination model

This is the post-print version of the final paper published in Molecular Immunology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.In this study, we investigated the potential molecular and immunological differences of a recombinant fusion protein (Hybrid-1), comprising of the immunodominant antigens Ag85B and ESAT-6 from Mycobacterium tuberculosis, derived from two different expression systems, namely Mycobacterium smegmatis and Escherichia coli. The fusion protein was successfully expressed and purified from both bacterial hosts and analyzed for any host-dependent post-translational modifications that might affect the immunogenicity of the protein. We investigated the immunogenicity of Hybrid-1 expressed in the two host species in a murine vaccination model, together with a reference standard Hybrid-1 (expressed in E. coli) from the Statens Serum Institut. No evidence of any post-translation modification was found in the M. smegmatis-derived Hybrid-1 fusion protein, nor were there any significant differences in the T-cell responses obtained to the three antigens analyzed. In conclusion, the Hybrid-1 fusion protein was successfully expressed in a homologous expression system using M. smegmatis and this system is worth considering as a primary source for vaccination trials, as it provided protein of excellent yield, stability and free from lipopolysaccharide.European TB-VAC consortium and Brunel University

Is Mitigation Translocation an Effective Strategy for Conserving Common Chuckwallas?

Mitigation translocation remains a popular conservation tool despite ongoing debate regarding its utility for population conservation. To add to the understanding of the effectiveness of mitigation translocation, in 2017 and 2018 we monitored a population of protected common chuckwallas (Sauromalus ater) following translocation away from the area of construction of a new highway near the South Mountains, Phoenix, Arizona, USA. We removed chuckwallas from the construction right-of-way, paint-marked and pit-tagged them, and then released them in a nearby municipal preserve. We deployed very high frequency radio-telemetry transmitters on a sub-sample of 15 translocated adult chuckwallas. We monitored the radio-marked chuckwallas once a day at 1- to 3-day intervals for up to 46 days to document survival, body mass, and post-release movements. The average distance moved following translocation was 359 ± 53 m. Using minimum convex polygons, the average home range size of translocated lizards was 0.9 ± 0.3 ha, which was 18–45 times larger than expected for the species. Following translocations, we surveyed the translocation sites 1 month later and again 1 year later to determine the presence of translocated chuckwallas. Translocated individuals were rarely observed a second time: in 2017, only 11 of 160 translocated chuckwallas were seen again, and in 2018, only 11 of 192 translocated chuckwallas were detected. In the light of low recapture rate, consistent loss of body mass, and large movements of marked lizards, we conclude that survival of translocated chuckwallas was low over a single year. In the future, efficacy of mitigation translocation could be better evaluated by assessing the spatial ecology of both resident and translocated individuals simultaneously using radio-telemetry

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress

Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions