The missing N1 or jittered P2: Electrophysiological correlates of pattern glare in the time and frequency domain

Excessive sensitivity to certain visual stimuli (cortical hyperexcitability) is associated with a number of neurological disorders including migraine, epilepsy, multiple sclerosis, autism and possibly dyslexia. Others show disruptive sensitivity to visual stimuli with no other obvious pathology or symptom profile (visual stress) which can extend to discomfort and nausea. We used event-related potentials (ERPs) to explore the neural correlates of visual stress and headache proneness. We analysed ERPs in response to thick (0.37 cycles per degree [c/deg]), medium (3 c/deg) and thin (12 c/deg) gratings, using mass univariate analysis, considering three factors in the general population: headache proneness, visual stress and discomfort. We found relationships between ERP features and the headache and discomfort factors. Stimulus main effects were driven by the medium stimulus regardless of participant characteristics. Participants with high discomfort ratings had larger P1 components for the initial presentation of medium stimuli, suggesting initial cortical hyperexcitability that is later suppressed. The participants with high headache ratings showed atypical N1-P2 components for medium stripes relative to the other stimuli. This effect was present only after repeated stimulus presentation. These effects were also explored in the frequency domain, suggesting variations in intertrial theta band phase coherence. Our results suggest that discomfort and headache in response to striped stimuli are related to different neural processes; however, more exploration is needed to determine whether the results translate to a clinical migraine population

Health impacts of ambient biomass smoke in Tasmania, Australia

The island state of Tasmania has marked seasonal variations of fine particulate matter (PM2.5) concentrations related to wood heating during winter, planned forest fires during autumn and spring, and bushfires during summer. Biomass smoke causes considerable health harms and associated costs. We estimated the historical health burden from PM2.5 attributable to wood heater smoke (WHS) and landscape fire smoke (LFS) in Tasmania between 2010 and 2019. We calculated the daily population level exposure to WHS- and LFS-related PM2.5 and estimated the number of cases and health costs due to premature mortality, cardiorespiratory hospital admissions, and asthma emergency department (ED) visits. We estimated 69 deaths, 86 hospital admissions, and 15 asthma ED visits, each year, with over 74% of impacts attributed to WHS. Average yearly costs associated with WHS were of AUD$293 million and AUD$ 16 million for LFS. The latter increased up to more than AUD$ 34 million during extreme bushfire seasons. This is the first study to quantify the health impacts attributable to biomass smoke for Tasmania. We estimated substantial impacts, which could be reduced through replacing heating technologies, improving fire management, and possibly implementing integrated strategies. This would most likely produce important and cost-effective health benefits

Using digital technology to protect health in prolonged poor air quality episodes: a case study of the AirRater App during the Australian 2019–20 fires

In the southern hemisphere summer of 2019–20, Australia experienced its most severe bushfire season on record. Smoke from fires affected 80% of the population, with large and prolonged exceedances of the Australian National Air Quality Standard for fine particulate matter (PM2.5) recorded in all major population centers. We examined if AirRater, a free smartphone app that reports air quality and tracks user symptoms in near real‐time, assisted those populations to reduce their smoke exposure and protect their health. We distributed an online survey to over 13,000 AirRater users to assess how they used this information during the 2019-20 bushfire season, and why it was helpful to aid decision‐making in reducing personal smoke exposure. We received responses from 1732 users (13.3%). Respondents reported the app was highly useful, supporting informed decision‐making regarding daily activities during the smoke‐affected period. Commonly reported activities supported by information provided through the app were staying inside (76%), rescheduling or planning outdoor activities (64%), changing locations to less affected areas (29%) and informing decisions on medication use (15%). Innovative and easy‐to‐use smartphone apps such as AirRater, that provide individual‐level and location‐specific data, can enable users to reduce their exposure to environmental hazards and therefore protect their health

Increased MicroRNA-34b and -34c Predominantly Expressed in Stromal Tissues Is Associated with Poor Prognosis in Human Colon Cancer

published_or_final_versio

Using smartphone technology to reduce health impacts from atmospheric environmental hazards

Background: Global environmental change is exacerbating human vulnerability to adverse atmospheric conditions including air pollution, aeroallergens such as pollen, and extreme weather events. Public information and advisories are a central component of responses to mitigate the human impacts of environmental hazards. Digital technologies are emerging as a means of providing personalised, timely and accessible warnings. Method: We describe AirRater, an integrated online platform that combines symptom surveillance, environmental monitoring, and notifications of changing environmental conditions via a free smartphone app. It was developed and launched in Tasmania, Australia (population 510,000), with the aim of reducing health impacts and improving quality of life in people with conditions such as asthma and allergic rhinitis. We present environmental data, user uptake and results from three online evaluation surveys conducted during the first 22 months of operation, from October 2015 through August 2017.Results: There were 3,443 downloads of the app from all parts of Tasmania. Of the 1,959 individuals who registered, 79% reported having either asthma or allergic rhinitis. Downloads increased during adverse environmental conditions and following publicity. Symptom reports per active user were highest during spring (72%), lowest in autumn (37%) and spiked during periods of reduced air quality. In response to online surveys, most users reported that the app was useful and had improved their understanding of how environmental conditions affect their health, and in some cases had prompted action such as the timely use of medication.Conclusion: Active engagement and consistent positive feedback from users demonstrates the potential for considerable individual clinical and wider public health benefits from integrated and personalised monitoring systems such as AirRater. The perceived health benefits require objective verification, and such systems need to address several challenges in providing timely, reliable and valid environmental data

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment

Tumour-associated microglia/macrophages (TAM) are the most numerous non-neoplastic populations in the tumour microenvironment in glioblastoma multiforme (GBM), the most common malignant brain tumour in adulthood. The mTOR pathway, an important regulator of cell survival/proliferation, is upregulated in GBM, but little is known about the potential role of this pathway in TAM. Here, we show that GBM-initiating cells induce mTOR signalling in the microglia but not bone marrow-derived macrophages in both in vitro and in vivo GBM mouse models. mTOR-dependent regulation of STAT3 and NF-κB activity promotes an immunosuppressive microglial phenotype. This hinders effector T-cell infiltration, proliferation and immune reactivity, thereby contributing to tumour immune evasion and promoting tumour growth in mouse models. The translational value of our results is demonstrated in whole transcriptome datasets of human GBM and in a novel in vitro model, whereby expanded-potential stem cells (EPSC)-derived microglia-like cells are conditioned by syngeneic patient-derived GBM-initiating cells. These results raise the possibility that microglia could be the primary target of mTOR inhibition, rather than the intrinsic tumour cells in GBM

Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants

BACKGROUND: Airway colonization of mechanically ventilated very low birth weight infants (birth weight < 1500 grams) by Ureaplasma urealyticum (Uu) is associated with an increased risk of bronchopulmonary dysplasia (BPD). While Uu is sensitive to erythromycin in vitro, the efficacy of intravenous (IV) erythromycin to eliminate Uu from the airways has not been studied. METHODS: 17 very low birth weight infants with Uu positive tracheal aspirate (TA) cultures were randomized to either 5 (8 infants) or 10 days (9 infants) of IV erythromycin lactobionate (40 mg/kg/day in 3 divided doses). Tracheal aspirate cultures for Uu were performed on days 0, 5, 10 and 15. RESULTS: Intravenous erythromycin failed to eliminate airway colonization in a large proportion of infants regardless of whether they received 5 or 10 days of treatment. Ureaplasma urealyticum was isolated from 4/15 (27%) of TAs obtained at 5 days, 5/12 TAs (42%) obtained at 10 days and 6/11(55%) TAs obtained at 15 days (combined group data). CONCLUSIONS: Erythromycin administered IV does not eliminate Uu from the airways in a large proportion of infants. Failure of erythromycin to eliminate Uu from the airways may contribute to the lack of efficacy of this drug in reducing the incidence of BPD in very low birth weight infants