Are we meeting the needs of vulnerable children? Distribution of speech-language pathology services on the Gold Coast, Australia.

BACKGROUND: Compared to national averages, the Gold Coast, Australia, has a proportionately higher number of children entering their first year of primary school with 'at risk' or 'vulnerable' language skills. This paper investigates the distribution of paediatric speech-language pathology (SLP) services on the Gold Coast, relative to children's language and cognitive skills, and socioeconomic status (SES). METHODS: SLP service locations were identified through national association data and a manual search and mapped against SES and Australian Early Development Census data, for language and cognitive skills. RESULTS: Data for 7595 children was included, with 943 (12.4%) at risk and 780 (12.6%) vulnerable for language and cognitive skills. A total of 75 SLPs were identified (85.3% private, 14.6% public), which is 1 SLP to every 23 children who might have current or impending speech, language and communication needs. Fewer services were available in areas where vulnerable children were located and most were private providers, leading to further potential barriers to service access. CONCLUSIONS: The number of SLP services located on the Gold Coast is inadequate to meet the needs of children with language and cognitive skill vulnerabilities. Consideration of how services might be distributed is explored and warrants further consideration.

A behavioural and ERP investigation of the wearable camera photo review in autobiographical memory.

Wearable camera photo review has successfully been used to enhance memory, yet very little is known about the underlying mechanisms. Here, the sequential presentation of wearable camera photos - a key feature of wearable camera photo review - is examined using behavioural and EEG measures. Twelve female participants were taken on a walking tour, stopping at a series of predefined targets, while wearing a camera that captured photographs automatically. A sequence of four photos leading to these targets was selected (∼ 200 trials) and together with control photos, these were used in a recognition task one week later. Participants' recognition performance improved with the sequence of photos (measured in hit rates, correct rejections, & sensitivity), revealing for the first time, a positive effect of sequence of photos in wearable camera photo review. This has important implications for understanding the sequential and cumulative effects of cues on episodic remembering. An old-new ERP effect was also observed over visual regions for hits vs. correct rejections, highlighting the importance of visual processing not only for perception but also for the location of activated memory representations.

BCAT-induced autophagy regulates Aß load through an interdependence of redox state and PKC phosphorylation-implications in Alzheimer's disease.

Leucine, nutrient signal and substrate for the branched chain aminotransferase (BCAT) activates the mechanistic target of rapamycin (mTORC1) and regulates autophagic flux, mechanisms implicated in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease (AD). BCAT is upregulated in AD, where a moonlighting role, imparted through its redox-active CXXC motif, has been suggested. Here we demonstrate that the redox state of BCAT signals differential phosphorylation by protein kinase C (PKC) regulating the trafficking of cellular pools of BCAT. We show inter-dependence of BCAT expression and proteins associated with the P13K/Akt/mTORC1 and autophagy signalling pathways. In response to insulin or an increase in ROS, BCATc is trafficked to the membrane and docks via palmitoylation, which is associated with BCATc-induced autophagy through PKC phosphorylation. In response to increased levels of BCATc, as observed in AD, amyloid ß (Aß) levels accumulate due to a shift in autophagic flux. This effect was diminished when incubated with leucine, indicating that dietary levels of amino acids show promise in regulating Aß load. Together these findings show that increased BCATc expression, reported in human AD brain, will affect autophagy and Aß load through the interdependence of its redox-regulated phosphorylation offering a novel target to address AD pathology.

The Importance of Genetics Experts in Optimizing Genetic Test Orders Through Prospective and Retrospective Reviews.

OBJECTIVES: To demonstrate the impact of genetics specialists on identifying test order errors and improving reimbursement for genetic testing. METHODS: Forty-four cases in which whole exome sequencing (WES) was performed but not reimbursed were reviewed by a genetic counselor through simulated prospective and retrospective reviews. RESULTS: Fifty-two percent of WES requests were ordered by nongenetics providers. Retrospective review revealed that 50% of cases were denied because of contractual constraints on billing. If review by a genetic counselor had occurred in real time, modifications or cancellations would have been recommended in 82% of the cases. CONCLUSIONS: A laboratory stewardship program involving genetics experts identified test order errors and opportunities for improved reimbursement and cost savings. Significant variables affected reimbursement, including inpatient status, payer criteria, and ordering provider specialty.

Engineering a bioluminescent bioreporter from an environmentally sourced mercury-resistant Enterobacter cloacae strain for the detection of bioavailable mercury.

AIM: Escherichia coli is the conventional choice as the host strain for whole-cell bioreporter construction due to its well-understood genetics and well-established cloning protocols. However, for real-world environmental biosensing applications, it is often beneficial to use a bacterial strain derived directly from the environment under study to better ensure chemical target specificity and optimal response time. The aim of this study was to develop a whole-cell bioreporter for detection of bioavailable mercury by replacing E. coli with a wild-type bacterial host derived from a soil environment. MATERIALS AND RESULTS: In this study, an Enterobacter cloacae strain isolated from soil derived from a municipal and electronic waste dumping site was engineered to serve as a bioluminescent bioreporter for mercury toxicity by linking its merR-like gene and promoter sequence to a reorganized luxABCDE gene cassette from Photorhabdus luminescens. This bioreporter, designated as E. cloacae DWH4lux , detected mercury (HgCl2 ) at a minimum concentration of 0·2 µg l-1 with a linear response profile being maintained between a range of 0·4-1600 µg l-1 (R2  = 0·9604) with a peak bioluminescent response occurring within 1 h after exposure. No significant synergistic or antagonistic influences were observed on the bioluminescent response by other contaminating metal elements. Enterobacter cloacae DWH4lux was also demonstrated to detect mercury effectively in artificially contaminated water sample with linear correlation (R2  = 0·9623). CONCLUSIONS: The results indicated that E. cloacae DWH4lux could detect mercury in quantities below the US Environmental Protection Agency's permitted limit values (2 µg l-1 ). Hence, it is concluded that E. cloacae DWH4lux has the potential to serve as an effective whole-cell bioreporter for the environmental monitoring of mercury contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new insight into the recruitment of mercury-tolerant bacterial hosts derived from environmental samples over the conventional lab-based E. coli host for the construction of mercury bioreporters. With improved response time and selectivity, the environmentally sourced bacteria can serve as an alternative host choice to improve biosensing technology in the near future.

Positivity bias in past and future episodic thinking: Relationship with anxiety, depression, and retrieval-induced forgetting.

Positivity biases in autobiographical memory and episodic future thinking are considered important in mental wellbeing and are reduced in anxiety and depression. The inhibitory processes underlying retrieval-induced forgetting (RIF) have been proposed to contribute to these biases. This investigation found reduced positivity in past and future thinking to be associated with reduced memory specificity alongside greater levels of anxiety, depression, and rumination. Most notably, however, RIF was found to significantly predict memory valence. This indicates that RIF may be important in maintaining such biases, facilitating the forgetting of negative memories when a positive item is actively retrieved.

Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti.

Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potential to modify virus acquisition in the mosquito. Interestingly, low density lipopolyprotein (LDL) levels are decreased during severe DENV infection. Accordingly, we hypothesized that LDL is a modifiable factor that can influence flavivirus acquisition in the mosquito. We found that LDL is endocytosed by Ae. aegypti cells in a dynamin-dependent manner. LDL is also endocytosed by midgut epithelial cells and accumulates at the luminal midgut epithelium during bloodmeal digestion. Importantly, pretreatment with LDL, but not high density lipopolyprotein (HDL), significantly inhibited both DENV and ZIKV infection in vitro, and LDL inhibited ZIKV infection in vivo. This study identifies human LDL or 'bad cholesterol' as a modifiable factor that can inhibit flavivirus acquisition in Ae. aegypti. Identification of modifiable blood factors and critical cellular interactions that mediate pathogen acquisition may lead to novel strategies to disrupt the transmission cycle of vector-borne diseases.

Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube.

BCAA Metabolism and NH3 Homeostasis.

The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur. Efficient regulation of these pathways is mediated through the redox environment and phosphorylation in response to dietary and hormonal stimuli. The wide distribution of these proteins allows for effective BCAA utilisation. We discuss how BCAT, BCKDC, and glutamate dehydrogenase operate in supramolecular complexes, allowing for efficient channelling of substrates. The role of BCAAs in brain metabolism is highlighted in rodent and human brain, where differential expression of BCATm indicates differences in nitrogen metabolism between species. Finally, we introduce a new role for BCAT, where a change in function is triggered by oxidation of its redox-active switch. Our understanding of how BCAA metabolism and nitrogen transfer is regulated is important as many studies now point to BCAA metabolic dysregulation in metabolic and neurodegenerative conditions.

Estimating Resource Requirements to Staff a Response to a Medium to Large Outbreak of Foot and Mouth Disease in Australia.

A recent report to the Australian Government identified concerns relating to Australia's capacity to respond to a medium to large outbreak of FMD. To assess the resources required, the AusSpread disease simulation model was used to develop a plausible outbreak scenario that included 62 infected premises in five different states at the time of detection, 28 days after the disease entered the first property in Victoria. Movements of infected animals and/or contaminated product/equipment led to smaller outbreaks in NSW, Queensland, South Australia and Tasmania. With unlimited staff resources, the outbreak was eradicated in 63 days with 54 infected premises and a 98% chance of eradication within 3 months. This unconstrained response was estimated to involve 2724 personnel. Unlimited personnel was considered unrealistic, and therefore, the course of the outbreak was modelled using three levels of staffing and the probability of achieving eradication within 3 or 6 months of introduction determined. Under the baseline staffing level, there was only a 16% probability that the outbreak would be eradicated within 3 months, and a 60% probability of eradication in 6 months. Deployment of an additional 60 personnel in the first 3 weeks of the response increased the likelihood of eradication in 3 months to 68%, and 100% in 6 months. Deployment of further personnel incrementally increased the likelihood of timely eradication and decreased the duration and size of the outbreak. Targeted use of vaccination in high-risk areas coupled with the baseline personnel resources increased the probability of eradication in 3 months to 74% and to 100% in 6 months. This required 25 vaccination teams commencing 12 days into the control program increasing to 50 vaccination teams 3 weeks later. Deploying an equal number of additional personnel to surveillance and infected premises operations was equally effective in reducing the outbreak size and duration.

Are rehabilitation services for patients in UK eye clinics adequate? A survey of eye care professionals.

PURPOSE: The purpose of this study is to determine whether specific services such as emotional and family support are currently available in the United Kingdom for people with visual impairment. METHODS: A validated online survey was created and distributed to clinical staff in eye clinics (for example, ophthalmologists and optometrists) and rehabilitation staff (for example, social and rehabilitation workers) in the community, who worked with people with visual impairment. A total of 67 clinical and 42 rehabilitation staff completed the entire survey online. RESULTS: Only 67% of the respondents claimed their clinics provide emotional support and 44% of respondent's clinics provided family support. Clinical and rehabilitation staff have differences in opinion over what constitutes an essential service for a visually impaired patient. Rehabilitation staff considered emotional support and referral to social services as essential more often than clinical staff (P<0.05). There is some confusion over the type of personnel who provides each type of service, with some services showing substantial repetition. CONCLUSION: In the clinics sampled, there appears to be an underprovision of emotional support (attentive listening plus constructive suggestions) and family support (emotional support and advice for family members) for visually impaired patients in the United Kingdom. There also seems to be some discrepancy in services that eye care professionals feel are available and previous reports by visually impaired patients of the service they receive. There is a need to develop standardised pathways across the United Kingdom, to solve some of these issues.

Open access: a new model for publishing in the pharmacological sciences.

CPT: Pharmacometrics & Systems Pharmacology (CPT:PSP) is an online-only, open access (OA) journal, which means that anyone, anywhere in the world, can access, download, print out, and read articles published here immediately upon publication on the journal's website at Nature and simultaneous deposit in the public-access repository, PubMed Central. Using a Creative Commons license for authors, CPT:PSP permits authors to retain copyright in their articles and permits readers to download and reuse (with attribution) tables, data, and other elements of a paper. This Perspective provides an introduction to authors and readers of this new ASCPT journal about this approach to publishing.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e7; doi:10.1038/psp.2012.7; advance online publication 26 September 2012.

Achieving a narrow size distribution of Au particles at a precise depth in SiO2 by segregation of Au precipitates.

We propose a new method of confining Au nanoparticles of a narrow size distribution at a precise depth in an SiO2 matrix. The process involves the formation of nanocavities in silicon by hydrogen implantation and annealing (at 850 degrees C), followed by Au gettering to and precipitation in such cavities and a wet oxidation at 900 degrees C. Starting with a silicon-on-insulator wafer, Au precipitates can be segregated behind a growing Si/SiO2 interface during wet oxidation and ultimately trapped in SiO2 at the front interface of a buried oxide layer. The shape of the precipitates has been examined by transmission electron microscopy and found to be spherical. The average diameters of these precipitates before and after oxidation have been determined as around 15 nm and 30 nm, respectively.

Replication and assembly of human papillomaviruses.

Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic "raft" culture. Research producing synthetic papillomavirus particles--such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)--has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure.

In-vitro analysis of the dissolution kinetics and systemic availability of plutonium ingested in the form of 'hot' particles from the Semipalatinsk NTS.

In-vitro leaching of radioactive 'hot' particles isolated from soils sampled at the Semipalatinsk Nuclear Test Site has been carried out in order to evaluate the fraction of plutonium activity released into simulated human stomach and small intestine fluids during digestion. Characterisation of the particles (10-100 Bq(239,240)Pu) and investigation of their dissolution kinetics in simulated fluids has been accomplished using a combination of high-resolution alpha-spectrometry, gamma-spectrometry and liquid scintillation counting. The results of these analyses indicate that plutonium transfer across the human gut following the ingestion of 'hot' particles can be up to two orders of magnitude lower than that expected for plutonium in a more soluble form, and show that for areas affected by local fallout, use of published ingestion dose coefficients, together with bulk radionuclide concentrations in soil, may lead to a considerable overestimation of systemic uptake via the ingestion pathway.

Does Clinical Pharmacology & Therapeutics' conflict of interest policy protect the reader?

In this issue the Clinical Pharmacology & Therapeutics (CPT) Conflict of Interest (COI) policy is published in full. Conway describes the background of developing the policy, what it is designed to accomplish, and how it will be implemented.

The radioactive autopsy: safe working practices.

Autopsy cases involving individuals retaining radioactive substances are fortunately rare, but when they occur they can impose significant radiation safety and legal requirements. This review aims to improve the understanding of these issues so that appropriate precautions are implemented when necessary. This review describes the properties of ionizing radiations, natural and man-made sources of ionizing radiation and its use in healthcare. It identifies the most likely circumstances leading to radioactive substances being present during autopsy and sources of information, including radiation protection advice. It discusses precautions that may need to be implemented prior to, during and following autopsy. Despite the issue of appropriate information to patients and next of kin, it is inevitable that some cases will be identified only at autopsy and it is important that robust local procedures are maintained. Information must be communicated to assist safe management of the body and liaison between relevant professional groups may be needed to standardize methods of communication. Provided that appropriate precautions are implemented, determined through consultation with a qualified expert in radiation protection and by completion of risk assessment, the radioactive autopsy can be undertaken safely and in compliance with relevant legislative requirements.