Maintaining a cognitive map in darkness : the need to fuse boundary knowledge with path integration

Spatial navigation requires the processing of complex, disparate and often ambiguous sensory data. The neurocomputations underpinning this vital ability remain poorly understood. Controversy remains as to whether multimodal sensory information must be combined into a unified representation, consistent with Tolman's "cognitive map", or whether differential activation of independent navigation modules suffice to explain observed navigation behaviour. Here we demonstrate that key neural correlates of spatial navigation in darkness cannot be explained if the path integration system acted independently of boundary (landmark) information. In vivo recordings demonstrate that the rodent head direction (HD) system becomes unstable within three minutes without vision. In contrast, rodents maintain stable place fields and grid fields for over half an hour without vision. Using a simple HD error model, we show analytically that idiothetic path integration (iPI) alone cannot be used to maintain any stable place representation beyond two to three minutes. We then use a measure of place stability based on information theoretic principles to prove that featureless boundaries alone cannot be used to improve localization above chance level. Having shown that neither iPI nor boundaries alone are sufficient, we then address the question of whether their combination is sufficient and - we conjecture - necessary to maintain place stability for prolonged periods without vision. We addressed this question in simulations and robot experiments using a navigation model comprising of a particle filter and boundary map. The model replicates published experimental results on place field and grid field stability without vision, and makes testable predictions including place field splitting and grid field rescaling if the true arena geometry differs from the acquired boundary map. We discuss our findings in light of current theories of animal navigation and neuronal computation, and elaborate on their implications and significance for the design, analysis and interpretation of experiments.

Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells

Stimulation of the androgen receptor via bioavailable androgens, including testosterone and testosterone metabolites, is a key driver of prostate development and the early stages of prostate cancer. Androgens are hydrophobic and as such require carrier proteins, including sex hormone-binding globulin (SHBG), to enable efficient distribution from sites of biosynthesis to target tissues. The similarly hydrophobic corticosteroids also require a carrier protein whose affinity for steroid is modulated by proteolysis. However, proteolytic mechanisms regulating the SHBG/androgen complex have not been reported. Here, we show that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to SHBG in glutathione S-transferase interaction analyses. Further, we demonstrate that active KLK4 and KLK14 cleave human SHBG at unique sites and in an androgen-dependent manner. KLK4 separated androgen-free SHBG into its two laminin G-like (LG) domains that were subsequently proteolytically stable even after prolonged digestion, whereas a catalytically equivalent amount of KLK14 reduced SHBG to small peptide fragments over the same period. Conversely, proteolysis of 5α-dihydrotestosterone (DHT)-bound SHBG was similar for both KLKs and left the steroid binding LG4 domain intact. Characterization of this proteolysis fragment by [(3)H]-labeled DHT binding assays revealed that it retained identical affinity for androgen compared with full-length SHBG (dissociation constant = 1.92 nM). Consistent with this, both full-length SHBG and SHBG-LG4 significantly increased DHT-mediated transcriptional activity of the androgen receptor compared with DHT delivered without carrier protein. Collectively, these data provide the first evidence that SHBG is a target for proteolysis and demonstrate that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.

Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients.

Alterations in innate immunity that predispose to chronic obstructive pulmonary disease (COPD) exacerbations are poorly understood. We examined innate immunity gene expression in peripheral blood polymorphonuclear leukocytes (PMN) and monocytes stimulated by Haemophilus influenzae and Streptococcus pneumoniae. Thirty COPD patients (15 rapid and 15 non-rapid lung function decliners) and 15 smokers without COPD were studied. Protein expression of IL-8, IL-6, TNF-α and IFN-γ (especially monocytes) increased with bacterial challenge. In monocytes stimulated with S. pneumoniae, TNF-α protein expression was higher in COPD (non-rapid decliners) than in smokers. In co-cultures of monocytes and PMN, mRNA expression of TGF-β1 and MYD88 was up-regulated, and CD14, TLR2 and IFN-γ down-regulated with H. influenzae challenge. TNF-α mRNA expression was increased with H. influenzae challenge in COPD. Cytokine responses were similar between rapid and non-rapid decliners. TNF-α expression was up-regulated in non-rapid decliners in response to H. influenzae (monocytes) and S. pneumoniae (co-culture of monocytes and PMN). Exposure to bacterial pathogens causes characteristic innate immune responses in peripheral blood monocytes and PMN in COPD. Bacterial exposure significantly alters the expression of TNF-α in COPD patients, although not consistently. There did not appear to be major differences in innate immune responses between rapid and non-rapid decliners.

OpenRatSLAM : an open source brain-based SLAM system

RatSLAM is a navigation system based on the neural processes underlying navigation in the rodent brain, capable of operating with low resolution monocular image data. Seminal experiments using RatSLAM include mapping an entire suburb with a web camera and a long term robot delivery trial. This paper describes OpenRatSLAM, an open-source version of RatSLAM with bindings to the Robot Operating System framework to leverage advantages such as robot and sensor abstraction, networking, data playback, and visualization. OpenRatSLAM comprises connected ROS nodes to represent RatSLAM’s pose cells, experience map, and local view cells, as well as a fourth node that provides visual odometry estimates. The nodes are described with reference to the RatSLAM model and salient details of the ROS implementation such as topics, messages, parameters, class diagrams, sequence diagrams, and parameter tuning strategies. The performance of the system is demonstrated on three publicly available open-source datasets.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses

Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48 h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24 h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48 h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6 h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48 h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6–48 h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.

Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

Rat meets iRat

Biorobotics has the potential to provide an integrated understanding from neural systems to behavior that is neither ethical nor technically feasible with living systems. Robots that can interact with animals in their natural environment open new possibilities for empirical studies in neuroscience. However, designing a robot that can interact with a rodent requires considerations that span a range of disciplines. For the rat's safety, the body form and movements of the robot need to take into consideration the safety of the animal, an appropriate size for the rodent arenas, and behaviors for interaction. For the robot's safety, its form must be robust in the face of typically inquisitive and potentially aggressive behaviors by the rodent, which can include chewing on exposed parts, including electronics, and deliberate or accidental fouling. We designed a rat-sized robot, the iRat (intelligent rat animat technology) for studies in neuroscience. The iRat is about the same size as a rat and has the ability to navigate autonomously around small environments. In this study we report the first interactions between the iRat and real rodents in a free exploration task. Studies with five rats show that the rats and iRat interact safely for both parties.

Lingodroids : learning terms for time

For humans and robots to communicate using natural language it is necessary for the robots to develop concepts and associated terms that correspond to the human use of words. Time and space are foundational concepts in human language, and to develop a set of words that correspond to human notions of time and space, it is necessary to take into account the way that they are used in natural human conversations, where terms and phrases such as `soon', `in a while', or `near' are often used. We present language learning robots called Lingodroids that can learn and use simple terms for time and space. In previous work, the Lingodroids were able to learn terms for space. In this work we extend their abilities by adding temporal variables which allow them to learn terms for time. The robots build their own maps of the world and interact socially to form a shared lexicon for location and duration terms. The robots successfully use the shared lexicons to communicate places and times to meet again.

Long summer days : grounded learning of words for the uneven cycles of real world events

Time and space are fundamental to human language and embodied cognition. In our early work we investigated how Lingodroids, robots with the ability to build their own maps, could evolve their own geopersonal spatial language. In subsequent studies we extended the framework developed for learning spatial concepts and words to learning temporal intervals. This paper considers a new aspect of time, the naming of concepts like morning, afternoon, dawn, and dusk, which are events that are part of day-night cycles, but are not defined by specific time points on a clock. Grounding of such terms refers to events and features of the diurnal cycle, such as light levels. We studied event-based time in which robots experienced day-night cycles that varied with the seasons throughout a year. Then we used meet-at tasks to demonstrate that the words learned were grounded, where the times to meet were morning and afternoon, rather than specific clock times. The studies show how words and concepts for a novel aspect of cyclic time can be grounded through experience with events rather than by times as measured by clocks or calendars

Ethanol sensitivity of thermally evaporated nanostructured WO3 thin films doped and implanted with Fe

Ethanol sensing performance of gas sensors made of Fe doped and Fe implanted nanostructured WO3 thin films prepared by a thermal evaporation technique was investigated. Three different types of nanostructured thin films, namely, pure WO3 thin films, iron-doped WO3 thin films by co-evaporation and Fe-implanted WO3 thin films have been synthesized. All the thin films have a film thickness of 300 nm. The physical, chemical and electronic properties of these films have been optimized by annealing heat treatment at 300ºC and 400ºC for 2 hours in air. Various analytical techniques were employed to characterize these films. Atomic Force Microscopy and Transmission Electron Microscopy revealed a very small grain size of the order 5-10 nm in as-deposited WO3 films, and annealing at 300ºC or 400ºC did not result in any significant change in grain size. This study has demonstrated enhanced sensing properties of WO3 thin film sensors towards ethanol at lower operating temperature, which was achieved by optimizing the physical, chemical and electronic properties of the WO3 film through Fe doping and annealing.

Mortality and cost outcomes of elderly trauma patients admitted to intensive care and the general wards of an Australian tertiary referral hospital

Mortality and cost outcomes of elderly intensive care unit (ICU) trauma patients were characterised in a retrospective cohort study from an Australian tertiary ICU. Trauma patients admitted between January 2000 and December 2005 were grouped into three major age categories: aged ≥65 years admitted into ICU (n=272); aged ≥65 years admitted into general ward (n=610) and aged <65 years admitted into ICU (n=1617). Hospital mortality predictors were characterised as odds ratios (OR) using logistic regression. The impact of predictor variables on (log) total hospital-stay costs was determined using least squares regression. An alternate treatment-effects regression model estimated the mortality cost-effect as an endogenous variable. Mortality predictors (P ≤0.0001, comparator: ICU ≥65 years, ventilated) were: ICU <65 not-ventilated (OR 0.014); ICU <65 ventilated (OR 0.090); ICU age ≥65 not-ventilated (OR 0.061) and ward ≥65 (OR 0.086); increasing injury severity score and increased Charlson comorbidity index of 1 and 2, compared with zero (OR 2.21 [1.40 to 3.48] and OR 2.57 [1.45 to 4.55]). The raw mean daily ICU and hospital costs in A$ 2005 (US$) for age <65 and ≥65 to ICU, and ≥65 to the ward were; for year 2000: ICU, $2717 (1462) and $2777 (1494); hospital, $1837 (988) and $1590 (855); ward $933 (502); for year 2005: ICU, $3202 (2393) and $3086 (2307); hospital, $1938 (1449) and $1914 (1431); ward $1180 (882). Cost increments were predicted by age ≥65 and ICU admission, increasing injury severity score, mechanical ventilation, Charlson comorbidity index increments and hospital survival. Mortalitycost-effect was estimated at -63% by least squares regression and -82% by treatment-effects regression model. Patient demographic factors, injury severity and its consequences predict both cost and survival in trauma. The cost mortality effect was biased upwards by conventional least squares regression estimation.

Auditor obligations in an evolving legal landscape

Purpose – The purpose of this paper is to look at auditor obligations to their clients and potentially to third parties such as investors, with a focus on the quality of financial disclosure in an evolving legal framework. Design/methodology/approach – The article outlines and compares established and emerging trends relative to information disclosure and contractual performance in parallel contexts where information asymmetry exists. In particular, this article considers the disclosure regime that has evolved in the insurance industry to address the substantial imbalance in the level of knowledge possessed by the insured in comparison to the prospective insurer. Abductive reasoning is used to identify causal constructs that explain the data pattern from which the theorised potential for judicial revision of the interpretation of “true and fair” in line with “good faith” in legal regulation is derived. Findings – The authors conclude that there is little doubt that a duty of good faith in relation to auditor-company contractual dealings and potentially a broader good faith duty to third parties such as investors in companies may be on the horizon. Originality/value – In the context of stated objectives by organisations such as the International Federation of Accountants to reconcile ethical and technical skills in the wake of the global financial crisis, there is an increased need to rebuild public and investor confidence in the underpinning integrity of financial reporting. This paper offers a perspective on one way to achieve this by recognising the similarities in the information asymmetry relationships in the insurance industry and how the notion of “good faith” in that relationship could be useful in the audit situation.

Success or failure : the NRAS

Many Australian families are unable to access homeownership. This is because house prices are very high to the severely or seriously unaffordable level. Therefore, many low income families will need to rely on affordable rental housing supply. The Australian governments introduced National Rental Affordability Scheme (NRAS) in July 2008. The scheme aims to increase the supply of affordable rental housing by 50,000 dwellings across Australia by June 2014. It provides financial incentive for investors to purchase new affordable housing that must be rented at a minimum of 20% below the market rent. The scheme has been in place for four years to June 2012. There are debates on the success or failure of the scheme. One argues that the scheme is more successful in Queensland but it failed to meet its aims in NSW. This paper examines NRAS incentive designed to encourage affordable housing supply in Australia and demonstrates reasons for developing properties that are crowded in areas where the land prices are relatively lower in the NSW using a discounted cash flow analysis in a hypothetical case study. The findings suggest that the high land values and the increasing cost of development were the main constraints of implementing the scheme in the NSW and government should not provide a flat rate subsidy which is inadequate to ensure that affordable housing projects in high cost areas.

A commentary on the current and future status of educational and developmental psychology in Australia

Educational and developmental psychology faces a number of current and future challenges and opportunities in Australia. In this commentary we consider the identity of educational and developmental psychology in terms of the features that distinguish it from other specialisations, and address issues related to training, specialist endorsement, supervision and rebating under the Australian government's Medicare system. The current status of training in Australia is considered through a review of the four university programs in educational and developmental psychology currently offered, and the employment destinations of their graduates. Although the need for traditional services in settings such as schools, hospitals, disability and community organisations will undoubtedly continue, the role of educational and developmental psychologists is being influenced and to some extent redefined by advances in technology, medicine, genetics, and neuroscience. We review some of these advances and conclude with recommendations for training and professional development that will enable Australian educational and developmental psychologists to meet the challenges ahead.