The temporal binding deficit hypothesis of autism

Frith has argued that people with autism show “weak central coherence,” an unusual bias toward piecemeal rather than configurational processing and a reduction in the normal tendency to process information in context. However, the precise cognitive and neurological mechanisms underlying weak central coherence are still unknown. We propose the hypothesis that the features of autism associated with weak central coherence result from a reduction in the integration of specialized local neural networks in the brain caused by a deficit in temporal binding. The visuoperceptual anomalies associated with weak central coherence may be attributed to a reduction in synchronization of high-frequency gamma activity between local networks processing local features. The failure to utilize context in language processing in autism can be explained in similar terms. Temporal binding deficits could also contribute to executive dysfunction in autism and to some of the deficits in socialization and communication

Searching for novel cell cycle regulators in Trypanosoma brucei with an RNA interference screen

<b>Background</b><br /> The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes Human African Trypanosomiasis. Its cell cycle is complex and not fully understood at the molecular level. The T. brucei genome contains over 6000 protein coding genes with >50% having no predicted function. A small scale RNA interference (RNAi) screen was carried out in Trypanosoma brucei to evaluate the prospects for identifying novel cycle regulators.<p></p> <b>Results</b><br /> Procyclic form T. brucei were transfected with a genomic RNAi library and 204 clones isolated. However, only 76 RNAi clones were found to target a protein coding gene of potential interest. These clones were screened for defects in proliferation and cell cycle progression following RNAi induction. Sixteen clones exhibited proliferation defects upon RNAi induction, with eight clones displaying potential cell cycle defects. To confirm the phenotypes, new RNAi cell lines were generated and characterised for five genes targeted in these clones. While we confirmed that the targeted genes are essential for proliferation, we were unable to unambiguously classify them as cell cycle regulators.<p></p> <b>Conclusion</b><br /> Our study identified genes essential for proliferation, but did not, as hoped, identify novel cell cycle regulators. Screening of the RNAi library for essential genes was extremely labour-intensive, which was compounded by the suboptimal quality of the library. For such a screening method to be viable for a large scale or genome wide screen, a new, significantly improved RNAi library will be required, and automated phenotyping approaches will need to be incorporated.<p></p&gt

A caspase-3 'death-switch' in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers

Novel anticancer drugs targeting key apoptosis regulators have been developed and are undergoing clinical trials. Pharmacodynamic biomarkers to define the optimum dose of drug that provokes tumor apoptosis are in demand; acquisition of longitudinal tumor biopsies is a significant challenge and minimally invasive biomarkers are required. Considering this, we have developed and validated a preclinical 'death-switch' model for the discovery of secreted biomarkers of tumour apoptosis using in vitro proteomics and in vivo evaluation of the novel imaging probe [ 18 F]ML-10 for non-invasive detection of apoptosis using positron emission tomography (PET). The 'death-switch' is a constitutively active mutant caspase-3 that is robustly induced by doxycycline to drive synchronous apoptosis in human colorectal cancer cells in vitro or grown as tumor xenografts. Deathswitch induction caused caspase-dependent apoptosis between 3 and 24 hours in vitro and regression of 'death-switched' xenografts occurred within 24 h correlating with the percentage of apoptotic cells in tumor and levels of an established cell death biomarker (cleaved cytokeratin-18) in the blood. We sought to define secreted biomarkers of tumor apoptosis from cultured cells using Discovery Isobaric Tag proteomics, which may provide candidates to validate in blood. Early after caspase-3 activation, levels of normally secreted proteins were decreased (e.g. Gelsolin and Midkine) and proteins including CD44 and High Mobility Group protein B1 (HMGB1) that were released into cell culture media in vitro were also identified in the bloodstream of mice bearing death-switched tumors. We also exemplify the utility of the death-switch model for the validation of apoptotic imaging probes using [ 18 F]ML-10, a PET tracer currently in clinical trials. Results showed increased tracer uptake of [ 18 F]ML-10 in tumours undergoing apoptosis, compared with matched tumour controls imaged in the same animal. Overall, the death-switch model represents a robust and versatile tool for the discovery and validation of apoptosis biomarkers. © 2013 Macmillan Publishers Limited. All rights reserved

The burden of hospitalized sports-related injuries in children: An Australian population-based study, 2005–2013

Background There is concern about recent increase and severity of sports-related injuries in children. Despite the benefits of sports participation, injuries may carry long-term health consequences. We aimed to evaluate the prevalence, characteristics and types of hospitalized sports-related injuries in children. Methods Population-based study of all acute sports-related injuries requiring hospitalization in children 5 to 15 years of age in New South Wales (NSW), Australia, 2005–2013. Health information was obtained from the NSW Admitted Patient Data Collection, a census of all hospital admissions from public and private hospitals. Children with a recorded ICD10-AM injury code (S00-T79) and sport-related activity code (U50-U70) were included. Prevalence and trend in injuries by age group, sporting code, body region affected and type of injury were assessed. Results There was a total of 20,034 hospitalizations for sports-related injuries (2.7% of all hospitalizations in children aged 5–15 years), involving 21,346 recorded injuries in 19,576 children. The overall population hospitalization period prevalence was 227 per 100,000 children aged 5–15 years in 2005–2013, remaining stable over time (RR 0.99; 95% CI 0.98–1.00). Football codes such as rugby league/union and soccer combined represented nearly two thirds of the total (60%). The most common body regions affected were the forearm (31%) head (15%) and hand injuries (13%). Fractures accounted for 65% of injuries followed by dislocations (10%) and traumatic brain injury (10%). Compared to other age groups, children aged 5–8 years had double the proportion of shoulder (15% vs. 7%) while 13–15 year olds had higher proportion of lower-leg (14% vs. 8%) and knee (6% vs.2%) injuries. One in seven injuries sustained while playing rugby league/union, baseball and hockey were traumatic brain injuries. A total of 444 (2.2%) of children had more than one hospitalization for sports-related injuries. Conclusion On average, six children were hospitalized every day for sports-related injuries in the last decade with trends remaining stable. The most common sports involved were football codes, one in three injuries involved the forearm and two thirds were fractures. These findings can be used to inform health policy and sporting governing bodies to target preventive interventions and promote safe sports participation in children

People with long-term conditions sharing personal health data via digital health technologies:a scoping review to inform design

The use of digital technology amongst people living with a range of long-term health conditions to support self-management has increased dramatically. More recently, digital health technologies to share and exchange personal health data with others have been investigated. Sharing personal health data with others is not without its risks: sharing data creates threats to the privacy and security of personal data and plays a role in trust, adoption and continued use of digital health technology. Our work aims to inform the design of these digital health technologies by investigating the reported intentions of sharing health data with others, the associated user experiences when using these digital health technologies and the trust, identity, privacy and security (TIPS) considerations for designing digital health technologies that support the trusted sharing of personal health data to support the self-management of long-term health conditions. To address these aims, we conducted a scoping review, analysing over 12,000 papers in the area of digital health technologies. We conducted a reflexive thematic analysis of 17 papers that described digital health technologies that support sharing of personal health data, and extracted design implications that could enhance the future development of trusted, private and secure digital health technologies.</p

Sintering of calcium phosphates with a femtosecond pulsed laser for hard tissue engineering

The authors acknowledge support from the sponsors of this work; the EPSRC LUMIN (EP/K020234/1) and EU-Marie-Curie-IAPP LUSTRE (324538) projects.Direct laser sintering on hard tissues is likely to open new pathways for personalised medicine. To minimise irradiation damage of the surrounding soft tissues, lasers operating at wavelengths that are ‘safe’ for the tissues and biomaterials with improved optical properties are required. In this work laser sintering is demonstrated with the use of an ultrafast, femtosecond (100 fs) pulsed laser operating at a wavelength of 1045 nm and two existing calcium phosphate minerals (brushite and hydroxyapatite) which have been improved after doping with iron (10 mol%). Femtosecond laser irradiation caused transformation of the Fe3+-doped brushite and Fe3+-doped HAp samples into β-calcium pyrophosphate and calcium-iron-phosphate, respectively, with simultaneous evidence for microstructural sintering and densification. After estimating the temperature profile at the surface of the samples we suggest that soft tissues over 500 μm from the irradiated zone would be safe from thermal damage. This novel laser processing provides a means to control the phase constitution and the morphology of the finished surfaces. The porous structure of β-pyrophosphate might be suitable for applications in bone regeneration by supporting osteogenic cell activity while, the densified Fe3+-rich calcium-iron-phosphate may be promising for applications like dental enamel restoration.PostprintPeer reviewe

Niche-specific regulation of central metabolic pathways in a fungal pathogen

To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis

Building and sustaining Work Engagement – A participatory action intervention to increase Work Engagement in nursing staff

This study evaluated whether a participatory action research intervention with nursing staff on acute care older people NHS wards in the UK was effective for increasing work engagement. Mediation analyses between job resources, (social support, influence in decision-making), job demands, work-related needs (autonomy, competence, relatedness), and work engagement explored the presumed psychological mechanisms underlying the intervention. A nonrandomised, matched control group, pre-test, post-test design involved three intervention and five control wards. A significant decrease in relatedness, and a borderline significant decrease in competence, was observed in the intervention group compared to the control group, with no effect on work engagement (N=45). Work-related needs mediated between resources and work engagement, supporting the Job Demands-Resources model and Self-Determination Theory as an underlying explanatory theory. Intervention implementation was difficult, highlighting the need for participant and organisational readiness for change, and strong management support. This is the first known study to apply participatory techniques to increase work engagement in nursing staff and explore the underlying explanatory psychological mechanisms, offering a novel means of taking work engagement research forward. Crucially, it highlights the challenges involved in intervention research and the importance of including evaluations of intervention implementation alongside statistical evaluations to avoid erroneous conclusions

Wintertime Spatial Distribution of Ammonia and its Emission Sources in the Great Salt Lake Region

Ammonium-containing aerosols are a major component of wintertime air pollution in many densely populated regions around the world. Especially in mountain basins, the formation of persistent cold-air pools (PCAPs) can enhance particulate matter with diameters less than 2.5 µm (PM2.5) to levels above air quality standards. Under these conditions, PM2.5 in the Great Salt Lake region of northern Utah has been shown to be primarily composed of ammonium nitrate; however, its formation processes and sources of its precursors are not fully understood. Hence, it is key to understanding the emission sources of its gas phase precursor, ammonia (NH3). To investigate the formation of ammonium nitrate, a suite of trace gases and aerosol composition were sampled from the NOAA Twin Otter aircraft during the Utah Winter Fine Particulate Study (UWFPS) in January and February 2017. NH3 was measured using a quantum cascade tunable infrared laser differential absorption spectrometer (QC-TILDAS), while aerosol composition, including particulate ammonium (pNH4), was measured with an aerosol mass spectrometer (AMS). The origin of the sampled air masses was investigated using the Stochastic Time-Inverted Lagrangian Transport (STILT) model and combined with an NH3 emission inventory to obtain model-predicted NHx (=NH3+pNH4) enhancements. Enhancements represent the increase in NH3 mixing ratios within the last 24 h due to emissions within the model footprint. Comparison of these NHx enhancements with measured NHx from the Twin Otter shows that modelled values are a factor of 1.6 to 4.4 lower for the three major valleys in the region. Among these, the underestimation is largest for Cache Valley, an area with intensive agricultural activities. We find that one explanation for the underestimation of wintertime emissions may be the seasonality factors applied to NH3 emissions from livestock. An investigation of inter-valley exchange revealed that transport of NH3 between major valleys was limited and PM2.5 in Salt Lake Valley (the most densely populated area in Utah) was not significantly impacted by NH3 from the agricultural areas in Cache Valley. We found that in Salt Lake Valley around two thirds of NHx originated within the valley, while about 30 % originated from mobile sources and 60 % from area source emissions in the region. For Cache Valley, a large fraction of NOx potentially leading to PM2.5 formation may not be locally emitted but mixed in from other counties