Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis

Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution.

Towards a consistent definition of a significant delta troponin with z-scores: A way out of chaos?

Aims: We assessed the diagnostic performance of z-scores to define a significant delta cardiac troponin (cTn) in a cohort of patients with well-defined clinical outcomes. Methods: We calculated z-scores, which are dependent on the analytical precision and biological variation, to report changes in cTn. We compared the diagnostic performances of a relative delta (%Δ), actual delta (Δ), and z-scores in 762 emergency department patients with symptoms of suspected acute coronary syndrome. cTn was measured with sensitive cTnI (Beckman Coulter), highly sensitive cTnI (Abbott), and highly sensitive cTnT (Roche) assays. Results: Receiver operating characteristic analysis showed no statistically significant differences in the areas under the curve (AUC) of z-scores and Δ with both superior compared to %Δ for all three assays (p<0.001). The AUCs of z-scores measured with the Abbott hs-cTnI (0.955) and Roche hs-cTnT (0.922) assays were comparable to Beckman Coulter cTnI (0.933) (p=0.272 and 0.640, respectively). The individualized Δ cut-off values that were required to emulate a z-score of 1.96 were: Beckman Coulter cTnI 30 ng/l, Abbott hs-cTnI 20 ng/l, and Roche hs-cTnT 7 ng/l. Conclusions: z-scores allow the use of a single cut-off value at all cTn levels, for both cTnI and cTnT and for sensitive and highly sensitive assays, with comparable diagnostic performances. This strategy of reporting significant changes as z-scores may obviate the need for the empirical development of assay-specific cut-off rules to define significant troponin changes.

WIL-power: Developing journalism students' intercultural communications and international reporting skills on field trips to Vietnam

This article examines journalism students' learning experience that is intercultural, immersive and intensive. Accounts of 'intercultural' experience date back to Herodotus of Halicarnassus; 'immersion' is integral to contemporary practice in language learning; and 'intensive' delivery has been refined to an art by postgraduate business education. Together they can be grouped under the broader pedagogical concept of work-integrated learning (WIL). This article examines two WIL projects that involved field trips by journalism students to Vietnam in 2012 and 2014, and their implications for future WIL initiatives.

Practice-based learning in community contexts: A collaborative exploration of pedagogical principles

The primary focus of this chapter is an exploration of four pedagogical principles emerging from a practice-based learning lab. Following an overview of community engaged learning and the Lab approach, the chapter is structured around a discussion of pedagogical principles related to (1) collaboration, (2) interdisciplinarity, (3) complexity and uncertainty and (4) reflection. Through a participatory action research (PAR) framework, students, academics and community partners have worked to identify and refine what it takes to support students negotiate complexity and uncertainty inherent in problems facing communities. It also examines the pedagogical strategies employed to facilitate collaboration across disciplines and professional contexts in ways that leverage difference and challenge values and practices.

U v U [2002] HCA 36: Commentary

This commentary offers a feminist analysis of relocation cases through the lens of U v U [2002] HCA 36, and with reference to the re-written judgment for the Australian Feminist Judgments project. First, the commentary considers the gendered nature of relocation cases, and analyses aspects of the reasoning and outcome of U v U that are of concern from a feminist perspective. Second, the commentary discusses how the re-written judgment addresses these concerns, thereby offering a feminist judgment on the issue of relocation in family law.

Peripapillary choroidal thickness in childhood

Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p<0.001) and sector position (p<0.001) in this population of children. The innermost annulus (closest to the edge of the optic disc) exhibited the thinnest choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p<0.001). RNFL thickness also varied significantly with annulus location and sector (p<0.001), and showed differences in thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle from the optic nerve head boundary. A significant thinning of the peripapillary choroid associated with myopia in childhood was also observed in both nasal and temporal regions. The changes in peripapillary RNFL and choroidal thickness associated with refractive error are consistent with a redistribution of these tissues occurring with myopic axial elongation in childhood.

Implementing improvements to health care services in the US

In a previous blog I was critical of the US health care system for not using cost-effectiveness information to plan their services. Today I’m going to talk about the implementation of innovation in health services, something the US does really well compared to Australia.

Recovery from first-episode psychosis and recovering self: A qualitative study

Objective The objective of this study was to explore the subjective factors associated with the experience of first-episode psychosis (FEP) and the very first stages of recovery to develop our understanding of this process and improve treatment outcomes. Method Interpretive Phenomenological Analysis was used to explore the experiences of 20 young people who had recently experienced FEP. Results Two broad superordinate themes captured essential thematic trends in the data: experiences of self-estrangement and self-consolidation. The concept of dialogical self was used to understand the effect of psychosis on self and the process of resuming familiar social positions to facilitate recovery. The concept of making meaning after traumatic events was also applied to the narratives of personal growth that participants formed. Those who reported subjective improvements in recovery were more likely to have developed a meaningful interpretation of their psychosis, strengthened relationships with others, and forged a stronger sense of self. Conclusions and Implications for Practice The experience of self-consolidation was strongly associated with the person’s resumption of familiar social roles and their ability to make meaning from their experience in a way that promoted personal growth. Although these processes are known to be part of personal recovery, this study highlights their importance in the very early stages of recovery immediately after the experience of FEP.

Hospital infection control units: Staffing, costs, and priorities

Background: This article describes infection prevention and control professionals’ (ICPs’) staffing levels, patient outcomes, and costs associated with the provision of infection prevention and control services in Australian hospitals. A secondary objective was to determine the priorities for infection control units. Methods: A cross-sectional study design was used. Infection control units in Australian public and private hospitals completed a Web-based anonymous survey. Data collected included details about the respondent; hospital demographics; details and services of the infection control unit; and a description of infection prevention and control-related outputs, patient outcomes, and infection control priorities. Results: Forty-nine surveys were undertaken, accounting for 152 Australian hospitals. The mean number of ICPs was 0.66 per 100 overnight beds (95% confidence interval, 0.55-0.77). Privately funded hospitals have significantly fewer ICPs per 100 overnight beds compared with publicly funded hospitals (P < .01). Staffing costs for nursing staff in infection control units in this study totaled $16,364,392 (mean, $380,566). Infection control units managing smaller hospitals (<270 beds) identified the need for increased access to infectious diseases or microbiology support. Conclusion: This study provides valuable information to support future decisions by funders, hospital administrators, and ICPs on service delivery models for infection prevention and control. Further, it is the first to provide estimates of the resourcing and cost of staffing infection control in hospitals at a national level. Copyright

Preoperative bathing or showering with skin antiseptics to prevent surgical site infection

Background Surgical site infections (SSIs) are wound infections that occur after invasive (surgical) procedures. Preoperative bathing or showering with an antiseptic skin wash product is a well-accepted procedure for reducing skin bacteria (microflora). It is less clear whether reducing skin microflora leads to a lower incidence of surgical site infection. Objectives To review the evidence for preoperative bathing or showering with antiseptics for preventing hospital-acquired (nosocomial) surgical site infections. Search methods For this fifth update we searched the Cochrane Wounds Group Specialised Register (searched 18 December 2014); the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014 Issue 11); Ovid MEDLINE (2012 to December Week 4 2014), Ovid MEDLINE (In-Process & Other Non-Indexed Citations December 18, 2014); Ovid EMBASE (2012 to 2014 Week 51), EBSCO CINAHL (2012 to December 18 2014) and reference lists of articles. Selection criteria Randomised controlled trials comparing any antiseptic preparation used for preoperative full-body bathing or showering with non-antiseptic preparations in people undergoing surgery. Data collection and analysis Two review authors independently assessed studies for selection, risk of bias and extracted data. Study authors were contacted for additional information. Main results We did not identify any new trials for inclusion in this fifth update. Seven trials involving a total of 10,157 participants were included. Four of the included trials had three comparison groups. The antiseptic used in all trials was 4% chlorhexidine gluconate (Hibiscrub/Riohex). Three trials involving 7791 participants compared chlorhexidine with a placebo. Bathing with chlorhexidine compared with placebo did not result in a statistically significant reduction in SSIs; the relative risk of SSI (RR) was 0.91 (95% confidence interval (CI) 0.80 to 1.04). When only trials of high quality were included in this comparison, the RR of SSI was 0.95 (95%CI 0.82 to 1.10). Three trials of 1443 participants compared bar soap with chlorhexidine; when combined there was no difference in the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Three trials of 1192 patients compared bathing with chlorhexidine with no washing, one large study found a statistically significant difference in favour of bathing with chlorhexidine (RR 0.36, 95%CI 0.17 to 0.79). The smaller studies found no difference between patients who washed with chlorhexidine and those who did not wash preoperatively. Authors' conclusions This review provides no clear evidence of benefit for preoperative showering or bathing with chlorhexidine over other wash products, to reduce surgical site infection. Efforts to reduce the incidence of nosocomial surgical site infection should focus on interventions where effect has been demonstrated.

Impact of particle formation on atmospheric ions and particle number concentrations in an urban environment

A measurement campaign was conducted from 3 to 19 December 2012 at an urban site of Brisbane, Australia. Size distribution of ions and particle number concentrations were measured to investigate the influence of particle formation and biomass burning on atmospheric ion and particle concentrations. Overall ion and particle number concentrations during the measurement period were found to be (-1.2 x 103 cm-3 | +1.6 x 103 cm-3) and 4.4 x 103, respectively. The results of correlation analysis between concentrations of ions and nitrogen oxides indicated that positive and negative ions originated from similar sources, and that vehicle exhaust emissions had a more significant influence on intermediate/large ions, while cluster ions rapidly attached to larger particles once emitted into the atmosphere. Diurnal variations in ion concentration suggested the enrichment of intermediate and large ions on new particle formation event days, indicating that they were involved in the particle formation processes. Elevated total ions, particularly larger ions, and particle number concentrations were found during biomass burning episodes. This could be due to the attachment of cluster ions onto accumulation mode particles or production of charged particles from biomass burning, which were in turn transported to the measurement site. The results of this work enhance scientific understanding of the sources of atmospheric ions in an urban environment, as well as their interactions with particles during particle formation processes.

A tsunami of unmet needs: Pancreatic and ampullary cancer patients’ supportive care needs and use of community and allied health services

Objective People diagnosed with pancreatic cancer have the worst survival prognosis of any cancer. No previous research has documented the supportive care needs of this population. Our objective was to describe people’s needs and use of support services and to examine whether these differed according to whether or not patients had undergone surgical resection. Methods Queensland pancreatic or ampullary cancer patients (n=136, 54% of those eligible) completed a survey which assessed 34 needs across 5 domains (SCNS-SF34) and use of health services. Differences by resection were compared with Chi-squared tests. Results Overall, 96% of participants reported having some needs. More than half reported moderate-to-high unmet physical (54%) or psychological (52%) needs whereas, health system/information (32%), patient care (21%) and sexuality needs (16%) were described less frequently. The three most frequently reported moderate-to-high needs included ‘not being able to do things they used to do’ (41%), ‘concerns about the worries of those close’ (37%), and ‘uncertainty about the future’ (30%). Patients with non-resectable disease reported greater individual information needs but their needs were otherwise similar to patients with resectable disease. Self-reported use of support was low; only 35% accessed information, 28%, 18% and 15% consulted a dietician, complementary medicine practitioner or mental health practitioner, respectively. Palliative care access was greater (59% vs 27%) among those with non-resectable disease. Conclusion Very high levels of needs were reported by people with pancreatic or ampullary cancer. Future work needs to elucidate why uptake of appropriate supportive care is low and which services are required.

Notes on the future of critical discourse studies

In How to Do Things with Words, Austin (1975) described marriages, sentencings and ship launchings as prototypes of performative utterance. What’s the appropriate speech act for launching an academic journal? First editions of journals tend to take a field as formed a priori, as having “come of age”, and state good intents to capture its best or most innovative work.

An evaluation of differential reinforcement of other behavior, differential reinforcement of incompatible behavior, and restitution for the management of aggressive behaviors

A 46 year old institutionalized retarded woman was referred for treatment because of frequent verbal abuse and physically aggressive behaviors. A multicomponent behavioral intervention consisting of differential reinforcement of other behaviors, differential reinforcement of incompatible behaviors, and restitution was implemented. A sequential withdrawal design was used in order to evaluate the effects of components of the original intervention, and to provide a measure of response maintenance. Results indicated a marked decrease in verbal abuse and elimination of physical aggression. Verbal abuse recurred when the restitution procedure was withdrawn. The relative efficacy of the different interventions is discussed with respect to the behavioral management of aggression.

Biomonitoring of polycyclic aromatic hydrocarbons exposure in small groups of residents in Brisbane, Australia and Hanoi, Vietnam, and those travelling between the two cities

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse health outcomes. Concentrations of urinary PAH metabolites (OH-PAHs) provide an integrated measure of human exposure to PAHs but measurement of urinary OH-PAHs has not been done in Australia and rarely in Vietnam, where air pollution is of concern. In this study, we assessed exposure to PAHs in 16 participants living in Brisbane, Australia and Hanoi, Vietnam, with 4 participants travelling between the two cities during the monitoring period. A total of 312 first morning urine samples were collected over 10 weeks and were analysed for nine OH-PAHs. Concentrations of the urinary OH-PAHs were 2–10 times higher in participants from Hanoi than those from Brisbane. For example, the median concentrations of 1-hydroxypyrene were 292 pg/mL in Hanoi, compared to 64 pg/mL in Brisbane. For participants travelling from Brisbane to Hanoi and back, differences in exposure to PAHs in these two cities resulted in corresponding changes of urinary OH-PAH concentrations, demonstrating that the more polluted environment in Hanoi was likely the source for higher PAH exposure there.