Developing a taxonomy of hazards and hazard mitigation strategies for Motorised mobility scooter users.

The increased use of motorised mobility scooters (MMSs) presents a road safety challenge as using a MMS has risks for the user, pedestrians, and other road users. In relation to enhancing MMS driving safety, much of the training and available literature focuses on training vehicular control. Equally important is the need to investigate higher-order cognitive skills involved in driving MMSs, particularly hazard perception. Through a large questionnaire study with MMS users, we develop a taxonomy of the types of hazard MMS users encounter when crossing roads and strategies that are used to negotiate these hazards. Whilst MMS experience modulated hazard perception and strategy use, a core set of hazards and strategies were identified that have policy and practice implications for training interventions and the built environment. Exploration of the advantages and disadvantages of MMS use indicated its impact on various wellbeing outcomes as well as some potential barriers to use.

HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression.

Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.

Association of Gestational Age at Birth With Subsequent Suspected Developmental Coordination Disorder in Early Childhood in China.

Importance: It remains unknown whether children born at different degrees of prematurity, early term, and post term might have a higher risk of developmental coordination disorder (DCD) compared with completely full-term children (39-40 gestational weeks). Objective: To differentiate between suspected DCD in children with different gestational ages based on a national representative sample in China. Design, Setting, and Participants: A retrospective cohort study was conducted in China from April 1, 2018, to December 31, 2019. A total of 152 433 children aged 3 to 5 years from 2403 public kindergartens in 551 cities of China were included in the final analysis. A multilevel regression model was developed to determine the strength of association for different gestational ages associated with suspected DCD when considering kindergartens as clusters. Main Outcomes and Measures: Children's motor performance was assessed using the Little Developmental Coordination Disorder Questionnaire, completed by their parents. Gestational age was determined according to the mother's medical records and divided into 7 categories: completely full term (39 to 40 weeks' gestation), very preterm (<32 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), late term (41 weeks), and post term (>41 weeks). Results: A total of 152 433 children aged 3 to 5 years (mean [SD] age, 4.5 [0.8] years), including 80 370 boys (52.7%) and 72 063 girls (47.3%), were included in the study. There were 45 052 children (29.6%) aged 3 years, 59 796 (39.2%) aged 4 years, and 47 585 (31.2%) aged 5 years. Children who were born very preterm (odds ratio [OR], 1.35; 95% CI, 1.23-1.48), moderately preterm (OR, 1.18; 95% CI, 1.02-1.36), late preterm (OR, 1.24; 95% CI, 1.16-1.32), early term (OR, 1.11; 95% CI, 1.06-1.16), and post term (OR, 1.17; 95% CI, 1.07-1.27) were more likely to be classified in the suspected DCD category on the Little Developmental Coordination Disorder Questionnaire than completely full-term children after adjusting for the same characteristics. Additionally, there was no association with suspected DCD in younger (aged 3 years) early-term and postterm children by stratified analyses. Conclusions and Relevance: In this cohort study, every degree of prematurity at birth, early-term birth, and postterm birth were associated with suspected DCD when compared with full-term birth. These findings have important implications for understanding motor development in children born at different gestational ages. Long-term follow-up and rehabilitation interventions should be considered for children born early and post term.

Syndecan-3 enhances anabolic bone formation through WNT signaling.

Osteoporosis is the most common age-related metabolic bone disorder, which is characterized by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however, anabolic therapeutics are few and their use is time restricted. Here, we report that Syndecan-3 increases new bone formation through enhancement of WNT signaling in osteoblasts. Young adult Sdc3-/- mice have low bone volume, reduced bone formation, increased bone marrow adipose tissue, increased bone fragility, and a blunted anabolic bone formation response to mechanical loading. This premature osteoporosis-like phenotype of Sdc3-/- mice is due to delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast-mediated bone resorption. Indeed, overexpressing Sdc3 in osteoblasts using the Col1a1 promoter rescues the low bone volume phenotype of the Sdc3-/- mice, and also increases bone volume in WT mice. Mechanistically, SDC3 enhances canonical WNT signaling in osteoblasts through stabilization of Frizzled 1, making SDC3 an attractive target for novel bone anabolic drug development.

A formant study of the alveolar versus retroflex contrast in three Central Australian languages: Stop, nasal, and lateral manners of articulation.

This study presents formant transition data from 21 speakers for the apical alveolar∼retroflex contrast in three neighbouring Central Australian languages: Arrernte, Pitjantjatjara, and Warlpiri. The contrast is examined for three manners of articulation: stop, nasal, and lateral /t ∼ ʈ/ /n ∼ ɳ/, and /l ∼ ɭ/, and three vowel contexts /a i u/. As expected, results show that a lower F3 and F4 in the preceding vowel signal a retroflex consonant; and that the alveolar∼retroflex contrast is most clearly realized in the context of an /a/ vowel, and least clearly realized in the context of an /i/ vowel. Results also show that the contrast is most clearly realized for the stop manner of articulation. These results provide an acoustic basis for the greater typological rarity of retroflex nasals and laterals as compared to stops. It is suggested that possible nasalization of the preceding vowel accounts for the poorer nasal consonant results, and that articulatory constraints on lateral consonant production account for the poorer lateral consonant results. Importantly, differences are noticed between speakers, and it is suggested that literacy plays a major role in maintenance of this marginal phonemic contrast.

Longitudinal associations between family identification, loneliness, depression, and sleep quality.

OBJECTIVES: The prevalence of depression and loneliness is increasing in Western nations, and both have been shown to cause poor sleep quality, with evidence suggesting that loneliness also predicts depression. The Social Cure perspective can shed light on these relationships and thus informs the present study. Specifically, it was hypothesized that the extent of participants' identification with a significant social group, their family, would positively predict sleep quality and that this relationship would be mediated by loneliness and depression. DESIGN: A two-lave longitudinal online survey was used. METHODS: Participants completed an online survey at T1 (N = 387) and 1 year later at T2 (N = 122) assessing the extent to which they identified with their family. Their loneliness, depressive symptomology, and sleep quality/insomnia severity were also measured. RESULTS: Consistent with predictions, cross-sectional and longitudinal serial mediation models indicated that family identification was a negative predictor of loneliness, which in turn was a positive predictor of depression, which predicted poor sleep quality/insomnia. CONCLUSIONS: This is the first Social Cure study to explore the mediated relationship between social identification and sleep quality. As well as advancing the Social Cure perspective, these results have implications for how health professionals understand, prevent, and treat sleep problems. Statement of contribution What is already known on this subject? The prevalence of depression and loneliness is increasing in Western nations, and both have been shown to cause poor sleep quality. Weak social networks have been shown to predict restless sleep over time, and that depressed mood mediates this relationship. What does this study add? Family identification negatively predicted poor sleep quality cross-sectionally. Depression and loneliness positively predicted poor sleep quality over time. Depression and loneliness mediated the family identification-sleep quality relationship over time.

Assessing children's speech using picture-naming: The influence of differing phonological variables on some speech outcomes.

PURPOSE: Sometimes, children's speech is judged as typical on picture-naming tests and not on other speech tests, even other picture-naming tests. This study attempts to explain this observation by examining the impact of increasing the numbers of polysyllabic words in a picture-naming test on the outcomes of percentages of consonants and vowels correct and phonological processes. METHOD: The participants were 283 randomly sampled, typically-developing children, aged 3-7-years. These Australian English speakers named pictures, yielding ∼166 selected words, varied for syllable number, stress and shape, which repeatedly sampled all consonants and vowels of Australian English. RESULT: Most mismatches occurred in di- and polysyllabic words, with few in monosyllabic words: the usual words in picture-naming speech tests. Significant age effects existed for percentages of consonants and vowels correct and for 12 of the 16 phonological processes investigated. Many age effects were present at 7 years; later than often reported. CONCLUSION: These findings imply that additional di- and polysyllabic words add value to routine speech testing. Further, children, especially school children, who "pass" speech tests dominated by monosyllabic words may benefit from further examination of their productions of di- and polysyllabic words before finalizing clinical judgements about their speech status.

An acoustic study of nasal consonants in three Central Australian languages.

This study presents nasal consonant data from 21 speakers of three Central Australian languages: Arrernte, Pitjantjatjara and Warlpiri. The six nasals considered are bilabial /m/, dental /n/, alveolar /n/, retroflex /ɳ/, alveo-palatal /ɲ/, and velar /ŋ/. Nasal formant and bandwidth values are examined, as are the locations of spectral minima. Several differences are found between the bilabial /m/ and the velar /ŋ/, and also the palatal /ɲ/. The remaining coronal nasals /n n ɳ/ are not well differentiated within the nasal murmur, but their average bandwidths are lower than for the other nasal consonants. Broader spectral shape measures (Centre of Gravity and Standard Deviation) are also considered, and comparisons are made with data for stops and laterals in these languages based on the same spectral measures. It is suggested that nasals are not as easily differentiated using the various measures examined here as are stops and laterals. It is also suggested that existing models of nasal consonants do not fully account for the observed differences between the various nasal places of articulation; and that oral formants, in addition to anti-formants, contribute substantially to the output spectrum of nasal consonants.

An acoustic study of multiple lateral consonants in three Central Australian languages.

This study presents dental, alveolar, retroflex, and palatal lateral /̪ll ɭ ʎ/ data from three Central Australian languages: Arrernte, Pitjantjatjara, and Warlpiri. Formant results show that the laminal laterals (dental /̪l/ and palatal /ʎ/) have a relatively low F1, presumably due to a high jaw position for these sounds, as well as higher F4. In addition, the palatal /ʎ/ has very high F2. There is relatively little difference in F3 between the four lateral places of articulation. However, the retroflex /ɭ/ appears to have slightly lower F3 and F4 in comparison to the other lateral sounds. Importantly, spectral moment analyses suggest that centre of gravity and standard deviation (first and second spectral moments) are sufficient to characterize the four places of articulation. The retroflex has a concentration of energy at slightly lower frequencies than the alveolar, while the palatal has a concentration of energy at higher frequencies. The dental is characterized by a more even spread of energy. These various results are discussed in light of different acoustic models of lateral production, and the possibility of spectral cues to place of articulation across manners of articulation is considered.

Using boreholes as windows into groundwater ecosystems.

Groundwater ecosystems remain poorly understood yet may provide ecosystem services, make a unique contribution to biodiversity and contain useful bio-indicators of water quality. Little is known about ecosystem variability, the distribution of invertebrates within aquifers, or how representative boreholes are of aquifers. We addressed these issues using borehole imaging and single borehole dilution tests to identify three potential aquifer habitats (fractures, fissures or conduits) intercepted by two Chalk boreholes at different depths beneath the surface (34 to 98 m). These habitats were characterised by sampling the invertebrates, microbiology and hydrochemistry using a packer system to isolate them. Samples were taken with progressively increasing pumped volume to assess differences between borehole and aquifer communities. The study provides a new conceptual framework to infer the origin of water, invertebrates and microbes sampled from boreholes. It demonstrates that pumping 5 m(3) at 0.4-1.8 l/sec was sufficient to entrain invertebrates from five to tens of metres into the aquifer during these packer tests. Invertebrates and bacteria were more abundant in the boreholes than in the aquifer, with associated water chemistry variations indicating that boreholes act as sites of enhanced biogeochemical cycling. There was some variability in invertebrate abundance and bacterial community structure between habitats, indicating ecological heterogeneity within the aquifer. However, invertebrates were captured in all aquifer samples, and bacterial abundance, major ion chemistry and dissolved oxygen remained similar. Therefore the study demonstrates that in the Chalk, ecosystems comprising bacteria and invertebrates extend from around the water table to 70 m below it. Hydrogeological techniques provide excellent scope for tackling outstanding questions in groundwater ecology, provided an appropriate conceptual hydrogeological understanding is applied.

Psychosocial risk factors which may differentiate between women with Functional Voice Disorder, Organic Voice Disorder and a Control group.

This study aimed to explore psychosocial factors contributing to the development of functional voice disorders (FVD) and those differentiating between organic voice disorders (OVD) and a non-voice-disordered control group. A case-control study was undertaken of 194 women aged 18-80 years diagnosed with FVD (n = 73), OVD (n = 55), and controls (n = 66). FVD women were allocated into psychogenic voice disorder (PVD) (n = 37) and muscle tension voice disorder (MTVD) (n = 36) for sub-group analysis. Dependent variables included biographical and voice assessment data, the number and severity of life events and difficulties and conflict over speaking out (COSO) situations derived from the Life Events and Difficulties Schedule (LEDS), and psychological traits including emotional expressiveness scales. Four psychosocial components differentiated between the FVD and control group accounting for 84.9% of the variance: severe events, moderate events, severe COSO, and mild COSO difficulties. Severe events, severe and mild COSO difficulties differentiated between FVD and OVD groups, accounting for 80.5% of the variance. Moderate events differentiated between PVD and MTVD sub-groups, accounting for 58.9% of the variance. Psychological traits did not differentiate between groups. Stressful life events and COSO situations best differentiated FVD from OVD and control groups. More refined aetiological studies are needed to differentiate between PVD and MTVD.

Investigating primary marine aerosol properties: CCN activity of sea salt and mixed inorganic-organic particles.

Sea spray particles ejected as a result of bubbles bursting from artificial seawater containing salt and organic matter in a stainless steel tank were sampled for size distribution, morphology, and cloud condensation nucleus (CCN) activity. Bubbles were generated either by aeration through a diffuser or by water jet impingement on the seawater surface. Three objectives were addressed in this study. First, CCN activities of NaCl and two types of artificial sea salt containing only inorganic components were measured to establish a baseline for further measurements of mixed organic-inorganic particles. Second, the effect of varying bubble residence time in the bulk seawater solution on particle size and CCN activity was investigated and was found to be insignificant for the organic compounds studied. Finally, CCN activities of particles produced from jet impingement were compared with those produced from diffuser aeration. Analyses indicate a considerable amount of organic enrichment in the jet-produced particles relative to the bulk seawater composition when sodium laurate, an organic surfactant, is present in the seawater. In this case, the production of a thick foam layer during impingement may explain the difference in activation and supports hypotheses that particle production from the two methods of generating bubbles is not equal.

An EPG study of palatal consonants in two Australian languages.

This study presents EPG (electro-palatographic) data on (alveo-)palatal consonants from two Australian languages, Arrernte and Warlpiri. (Alveo-)palatal consonants are phonemic for stop, lateral and nasal manners of articulation in both languages, and are laminal articulations. However, in Arrernte, these lamino-(alveo-)palatals contrast with lamino-dental consonants for all three manners of articulation (i.e., it is a double-laminal language), whereas in Warlpiri this laminal contrast does not exist (i.e., it is a single-laminal language). Data are analyzed according to manner of articulation, vowel context and phrase position. Results suggest that in the double-laminal languageArrernte,the (alveo-)palatal articulation is further back than in the single-laminal language Warlpiri, presumably due to the presence of the lamino-dental in theArrernte phoneme inventory. The lateral has the least contact in the back regions of the palate for both languages, but there is no significant difference in contact pattern between the stop and the nasal. However, results tentatively suggest that the nasal (alveo-)palatal is the most likely to show effects of prosodic or vocalic context, and it is suggested that this is due to the less strict airflow requirements for the nasal than for the stop or the lateral.

First report of human anisakidosis in Australia.

We present the first human case of anisakidosis acquired from eating locally caught fish in Australia. A 41-year-old woman experienced gastrointestinal pain, vomiting and diarrhoea of increasing severity over 3 weeks. All symptoms resolved spontaneously after a worm was passed in her faeces. Microscopic examination showed that it was a Contracaecum species larva of the family Anisakidae. Anisakidosis should be considered in patients with gastrointestinal symptoms who have recently eaten seafood.

A lateralized auditory evoked potential elicited when auditory objects are defined by spatial motion.

Scene analysis involves the process of segmenting a field of overlapping objects from each other and from the background. It is a fundamental stage of perception in both vision and hearing. The auditory system encodes complex cues that allow listeners to find boundaries between sequential objects, even when no gap of silence exists between them. In this sense, object perception in hearing is similar to perceiving visual objects defined by isoluminant color, motion or binocular disparity. Motion is one such cue: when a moving sound abruptly disappears from one location and instantly reappears somewhere else, the listener perceives two sequential auditory objects. Smooth reversals of motion direction do not produce this segmentation. We investigated the brain electrical responses evoked by this spatial segmentation cue and compared them to the familiar auditory evoked potential elicited by sound onsets. Segmentation events evoke a pattern of negative and positive deflections that are unlike those evoked by onsets. We identified a negative component in the waveform - the Lateralized Object-Related Negativity - generated by the hemisphere contralateral to the side on which the new sound appears. The relationship between this component and similar components found in related paradigms is considered.

Novel technology to provide an enriched therapeutic cell concentrate from bone marrow aspirate.

Current strategies to repair fractures rely on orthopaedic surgeons harvesting bone from one area of the body, typically pelvis and transferring it to the fracture site. The amount of tissue available is therefore limited, requiring a second surgical procedure and often causing the patient long term pain. An alternative approach is utilise therapeutic cells contained within bone marrow aspirate during the primary procedure. The number of therapeutic cells within a fresh aspirate is insufficient to provide clinically acceptable bone healing in a timescale that is satisfactory to the surgeon and the patient. Therefore methods to efficiently concentrate bone marrow in the clinical setting are required. Centrifugation is the current method of choice but has limitations in that it requires large capital equipment, servicing and there are potential issues of tissue contamination. We have developed a novel, acoustically-assisted filtration device that addresses these limitations, delivering a concentrated bone marrow in a point of care, single use, fully disposable, compact device. An additional advantage is that the level of concentration required can be specified by the end user. The resulting bone marrow concentrate has been characterised in terms of cell number, viability and osteogenic potential using flow cytometry and alkaline phosphatase assay. When compared to recent clinical studies using bone marrow to repair non-union fractures, the findings from our work suggest that the bone marrow concentrate is likely to be highly therapeutic and clinically efficacious as a bone fracture repair strategy. A product concept for use in the clinical setting is presented.

History of biological metal utilization inferred through phylogenomic analysis of protein structures.

The fundamental chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Using protein structure and comparative genomics, we elucidate several major influences this chemistry has had upon biology. All of life exhibits the same proteome size-dependent scaling for the number of metal-binding proteins within a proteome. This fundamental evolutionary constant shows that the selection of one element occurs at the exclusion of another, with the eschewal of Fe for Zn and Ca being a defining feature of eukaryotic proteomes. Early life lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins that catalyze electron transport and redox transformations. The development of protein structures for metal homeostasis coincided with the emergence of metal-specific structures, which predominantly bound metals abundant in the Archean ocean. Potentially, this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast, structures binding Cu and Zn evolved much later, providing further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic cellular biology, and Zn bioavailability may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics, and key hypotheses can be tested by alternative geochemical methods.

Selective attention modulates electrical responses to reversals of optic-flow direction.

Attended stimuli typically evoke larger event-related potentials (ERPs) than unattended stimuli. We previously reported an exception when an optic-flow pattern is interleaved with stationary dots. Reversals of motion direction evoked a larger N200 peak when attention was directed to the stationary dots. We replicated and further characterized this result: the N200 enhancement was eliminated when the dots moved randomly rather than in optic flow. The effect was also attenuated with isoluminant stimuli. Electrical source analysis suggested the attentional modulation of a configuration of dorsal extrastriate generators. The ERP evoked by reversals of optic flow may reflect the operation of independently configurable attentional filters within visual cortex.

Cutaneous larva migrans in infants in the Adelaide Hills.

Four infants aged between 8 and 13 months presented between November 2002 and May 2006 with dermatitis of the lower abdomen, perineum or buttocks. All lived in semi-rural properties in the Adelaide Hills and had not travelled outside South Australia. Wandering thread-like serpiginous tracks were evident on examination, consistent with a diagnosis of cutaneous larva migrans. No abnormalities were detected on full blood examination, Strongyloides stercoralis serology or faecal analysis. Treatment with oral albendazole resulted in rapid resolution of symptoms. An epidemiological survey was undertaken which suggested possums or millipedes may have been the source of nematode larvae, the precise nature of which is unclear but could include Parastrongyloides trichosuri and Rhabditis necromena.

Interaction of platelet-rich concentrate with bone graft materials: an in vitro study.

OBJECTIVE: Platelet-rich concentrate (PRC) is in routine use for orthopaedic and maxilofacial surgery and is frequently combined with bone graft materials to fill bony defects and enhance healing. Numerous studies have been performed investigating the efficacy of PRC to enhance bone healing in which a variety of graft materials have been combined with varying degrees of success. Here, we sought to determine the effect of combining PRC with different graft materials on human bone marrow stromal cell (hBMSC) proliferation, osteoblastic differentiation, and bone formation. METHODS: Our central hypothesis is that PRC is not a true osteogenic agent but rather is osteopromotive, with cell fate determination being dependent on additional signals derived from the microenvironment. Experiments were performed with low passage (maximum 3) hBMSCs that were maintained in the presence of ascorbic acid-2-phosphate and beta-glycerol phosphate. Dexamethasone was excluded from these studies. PRC and graft materials were retained within well inserts and clotted by addition of bovine thrombin. Cell proliferation was determined by DNA content, osteoblastic commitment, and differentiation by alkaline phosphatase activity and matrix mineralization. RESULTS: Combining PRC with the graft materials increased proliferation above that seen with the graft materials alone; however, only demineralized bone matrix (DBM) and allograft were capable of increasing proliferation above that seen with PRC alone. The increased proliferation observed in the presence of PRC coincided with decreased normalized alkaline phosphatase activity, suggesting decreased osteoblastic differentiation. However, at later time points, PRC increased mineralization compared with DBM, collagen, or beta tricalcium phosphate alone. When compared with PRC alone, addition of DBM or allograft decreased mineralization. Collagen gave rise to a small increase in mineralization, whereas beta tricalcium phosphate yielded the same level of mineralization as PRC alone. CONCLUSIONS: The data obtained from these in vitro investigations demonstrate that the cellular responses induced by PRC and bone graft materials in hBMSC can be significantly (positively or negatively) modified by adding the agents in combination. These in vitro data highlight the need to consider the potential interaction between biologic agents when added in combination.