Watershed features shape spatial patterns of fish tissue mercury in a boreal river network.

Freshwater mercury (Hg) contamination is a widespread environmental concern but how proximate sources and downstream transport shape Hg spatial patterns in riverine food webs is poorly understood. We measured total Hg (THg) in slimy sculpin (Cottus cognatus) across the Kuskokwim River, a large boreal river in western Alaska and home to subsistence fishing communities which rely on fish for primary nutrition. We used spatial stream network models (SSNMs) to quantify watershed and instream conditions influencing sculpin THg. Spatial covariates for local watershed geology and slope accounted for 55 % of observed variation in sculpin THg and evidence for downstream transport of Hg in sculpins was weak. Empirical semivariograms indicated these spatial covariates accounted for most spatial autocorrelation in observed THg. Watershed geology and slope explained up to 70 % of sculpin THg variation when SSNMs accounted for instream spatial dependence. Our results provide network-wide predictions for fish tissue THg based largely on publicly available geospatial data and open-source software for SSNMs, and demonstrate how these emerging models can be used to understand contaminant behavior in spatially complex aquatic ecosystems.

Mitigating delay due to capacity drop near freeway bottlenecks: Zones of influence of connected vehicles.

We present a novel perspective on how connected vehicles can reduce total vehicular delay arising due to the capacity drop phenomenon observed at fixed freeway bottlenecks. We analytically determine spatial regions upstream of the bottleneck, called zones of influence, where a pair of connected vehicles can use an event-triggered control policy to positively influence a measurable traffic macrostate, e.g., the total vehicular delay at bottlenecks. These analytical expressions are also able to determine the boundaries (called null and event horizons) of these spatial extents, outside of which a connected vehicle cannot positively influence the traffic macrostate. These concepts can help ensure that information is disseminated to connected vehicles in only those spatial regions where it can be used to positively impact traffic macrostates. Some scenarios examined in this study indicate that communication between connected vehicles may be required over a span of several kilometers to positively impact traffic flow and mitigate delays arising due to the capacity drop phenomenon.

Identification and characterisation of functional Kir6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

Slowly activating voltage-gated potassium current potentiation by ML277 is a novel cardioprotective intervention.

Cardiovascular disease is thought to account for nearly a third of deaths worldwide, with ischemic heart disease, including acute coronary syndromes such as myocardial infarction, accounting for 1.7 million deaths per year. There is a clear need for interventions to impart cardioprotection against ischemia. Here, we show that the slowly activating voltage-gated potassium current (IKs) potentiator ML277 imparts cardioprotection against ischemia in cellular and whole-heart models by modulating the action potential duration. In three different metabolic inhibition and reperfusion models, an increased contractile recovery and cell survival was observed with ML277, indicative of protection. Finally, ML277 reduced infarct size in an ex vivo Langendorff coronary ligation model, including if only applied on reperfusion. In conclusion, potentiation of the IKs with ML277 imparted a cardioprotection that was equivalent to the protection reported previously by ischemic preconditioning. These data suggest that IKs potentiation may be therapeutically useful in acute coronary syndromes.

Selective protein kinase C inhibition switches time-dependent glucose cardiotoxicity to cardioprotection.

Hyperglycaemia at the time of myocardial infarction has an adverse effect on prognosis irrespective of a prior diagnosis of diabetes, suggesting glucose is the damaging factor. In ex vivo models of ischaemia, we demonstrated that deleterious effects of acutely elevated glucose are PKCα/ß-dependent, and providing PKCα/ß are inhibited, elevated glucose confers cardioprotection. Short pre-treatments with high glucose were used to investigate time-dependent glucose cardiotoxicity, with PKCα/ß inhibition investigated as a potential mechanism to reverse the toxicity. Freshly isolated non-diabetic rat cardiomyocytes were exposed to elevated glucose to investigate the time-dependence toxic effects. High glucose challenge for >7.5 min was cardiotoxic, proarrhythmic and lead to contractile failure, whilst cardiomyocytes exposed to metabolic inhibition following 5-min high glucose, displayed a time-dependent protection lasting ∼15 min. This protection was further enhanced with PKCα/ß inhibition. Cardioprotection was measured as a delay in contractile failure and KATP channel activation, improved contractile and Ca2+ transient recovery and increased cell survival. Finally, the effects of pre-ischaemic treatment with high glucose in a whole-heart coronary ligation protocol, where protection was evident with PKCα/ß inhibition. Selective PKCα/ß inhibition enhances protection suggesting glycaemic control with PKC inhibition as a potential cardioprotective therapeutics in myocardial infarction and elective cardiac surgery.

GuitarPD: A Randomized Pilot Study on the Impact of Nontraditional Guitar Instruction on Functional Movement and Well-Being in Parkinson's Disease.

Playing musical instruments may have positive effects on motor, emotional, and cognitive deficits in patients with Parkinson's disease (PD). This pilot study examined the feasibility of a six-week nontraditional guitar instruction program for individuals with PD. Twenty-six participants with idiopathic PD (Age: 67.22 ± 8.07; 17 males) were randomly assigned to two groups (intervention first or 6 weeks of usual care control exposure) with stepwise exposure to the guitar intervention condition with cross-over at six weeks. Outcomes were assessed at baseline, 6, 12, and 18 weeks. Twenty-four participants completed the study. Combined analysis of the groups showed significant BDI-II improvement immediately after intervention completion (3.04 points, 95% CI [-5.2, -0.9], p = 0.04). PDQ-39 total quality of life scores improved from baseline to immediately postintervention 5.19 points (95% CI [-9.4, -1.0]) at trend significance (corrected p = 0.07). For Group 1 (exposed to the intervention first), MDS-UPDRS total scores improved by a mean of 8.04 points (95% CI [-12.4, -3.7], p = 0.004) and remained improved at 12 weeks by 10.37 points (95% CI [-14.7, -6.0], p < 0.001). This group also had significant improvements in mood and depression at weeks 6 and 12, remaining significant at week 18 (BDI-II: 3.75, 95% CI [-5.8, -1.7], p = 0.004; NeuroQoL-depression: 10.6, 95% CI [-4.9. -1.4], p = 0.004), and in anxiety at week 6 and week 18 (NeuroQoL; 4.42, 95% CI [-6.8, -2.1], p = 0.004; 3.58, 95% CI [-5.9, -1.2], p = 0.02, respectively). We found clinically and statistically significant improvements in mood/anxiety after 6 weeks of group guitar classes in individuals with PD. Group guitar classes can be a feasible intervention in PD and may improve mood, anxiety, and quality of life.

FGFR Inhibition Enhances Sensitivity to Radiation in Non-Small Cell Lung Cancer.

FGFRs are commonly altered in non-small cell lung cancer (NSCLC). FGFRs activate multiple pathways including RAS/RAF/MAPK, PI3K/AKT, and STAT, which may play a role in the cellular response to radiation. We investigated the effects of combining the selective FGFR 1-3 tyrosine kinase inhibitor AZD4547 with radiation in cell line and xenograft models of NSCLC. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, autophagy, cell cycle, and DNA damage signaling and repair assays. In vivo xenografts and IHC were used to confirm in vitro results. NSCLC cell lines demonstrated varying degrees of FGFR protein and mRNA expression. In vitro clonogenic survival assays showed radiosensitization with AZD4547 in two NSCLC cell lines. In these two cell lines, an increase in apoptosis and autophagy was observed with combined radiation and AZD4547. The addition of AZD4547 to radiation did not significantly affect γH2AX foci formation. Enhanced xenograft tumor growth delay was observed with the combination of radiation and AZD4547 compared with radiation or drug alone. IHC results revealed inhibition of pMAPK and pS6 and demonstrated an increase in apoptosis in the radiation plus AZD4547 group. This study demonstrates that FGFR inhibition by AZD4547 enhances the response of radiation in FGFR-expressing NSCLC in vitro and in vivo model systems. These results support further investigation of combining FGFR inhibition with radiation as a clinical therapeutic strategy.

Development and Utility of the Observational Research in Oncology Toolbox: Cancer Medications Enquiry Database-Healthcare Common Procedure Coding System (HCPCS).

PURPOSE: Health-care claims are of increasing utility as a rich, real-world data resource for conducting treatment-related cancer research. However, multiple dynamic coding nomenclatures exist, leading to study variability. To promote increased standardization and reproducibility, the National Cancer Institute (NCI) developed the Cancer Medications Enquiry Database (CanMED)-Healthcare Common Procedure Coding System (HCPCS) within the Observational Research in Oncology Toolbox. METHODS: The CanMED-HCPCS includes codes for oncology medications that a) have a US Food and Drug Administration-approved indication for cancer treatment or treatment-related symptom management; b) are present in National Comprehensive Cancer Network guidelines; or c) carry an orphan drug designation for treatment or management of cancer. Included medications and their HCPCS codes were primarily identified based on Center for Medicare and Medicaid Services annual HCPCS Indices (2012-2018). To demonstrate the utility of the CanMED-HCPCS, use of systemic treatment for stage II-IV colorectal cancer patients included in the Surveillance, Epidemiology, and End Results-Medicare data (2007-2013) was assessed. RESULTS: The CanMED-HCPCS (v2018) includes 332 HCPCS codes for cancer-related medications: chemotherapy (156), immunotherapy (74), hormonal therapy (54), and ancillary therapy (48). Observed treatment trends within the NCI Surveillance, Epidemiology, and End Results-Medicare data were as expected; utilization of each treatment type increased with stage, and immunotherapy was largely confined to use among stage IV patients. CONCLUSION: The CanMED-HCPCS provides a comprehensive resource that can be used by the research community to facilitate systematic identification of medications within claims or electronic health data using the HCPCS nomenclature and greater reproducibility of cancer surveillance and health services research.

Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns.

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED-National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immunotherapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I-IIIA (20 701) and stage IIIB-IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promoting more standardized and efficient treatment-related cancer research.

Fibroblast Growth Factor Receptors as Targets for Radiosensitization in Head and Neck Squamous Cell Carcinomas.

PURPOSE: We examined the capacity of the pan-fibroblast growth factor receptor (FGFR) inhibitor AZD4547 to augment radiation response across a panel of head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. METHODS AND MATERIALS: FGFR1, FGFR2, and FGFR3 RNA in situ hybridization expression was assessed in a cohort of HNSCC patient samples, cell lines, and patient-derived xenografts (PDXs). In vitro effects of AZD4547 and radiation on cell survival, FGFR signaling, apoptosis, autophagy, cell cycle, and DNA damage repair were evaluated. Reverse phase protein array was used to identify differentially phosphorylated proteins in cells treated with AZD4547. In vivo tumor responses were evaluated in cell lines and PDX models. RESULTS: FGFR1, FGFR2, and FGFR3 RNA in situ hybridization were expressed in 41%, 81%, and 89% of 107 oropharynx patient samples. Sensitivity to AZD4547 did not directly correlate with FGFR protein or RNA expression. In sensitive cell lines, AZD4547 inhibited p-MAPK in a time-dependent manner. Significant radiosensitization with AZD4547 was observed in cell lines that were sensitive to AZD4547. The mechanism underlying these effects appears to be multifactorial, involving inhibition of the MTOR pathway and subsequent enhancement of autophagy and activation of apoptotic pathways. Significant tumor growth delay was observed when AZD4547 was combined with radiation compared with radiation or drug alone in an FGFR-expressing HNSCC cell line xenograft and PDX. CONCLUSIONS: These findings suggest that AZD4547 can augment the response of radiation in FGFR-expressing HNSCC in vivo model systems. FGFR1 and FGFR2 may prove worthy targets for radiosensitization in HNSCC clinical investigations.

At what cost? How planned collisions with pedestrians may save lives.

Pedestrian avoidance algorithms often tacitly assume that the maneuver which minimizes collisions will also be the safest maneuver. This work shows that this is not always the case when considering pedestrian fatalities. Given the unavoidable uncertainty in vehicle motion, environmental parameters, and pedestrian behavior, emergency avoidance maneuvers often involve some chance of a collision. Maneuvers that aim to keep the vehicle as far away from the pedestrian as possible will theoretically minimize collisions; but if this strategy is followed and a collision occurs nonetheless, it will often be at a higher speed than would occur with alternative strategies. This is a result of the tires' friction ellipse which enforces a constraint between steering versus braking; for collision avoidance, braking must be reduced if pedestrian clearance is to be maximized. This work shows that in some common pedestrian collision situations, the net effect of this increase in vehicle speed for pure avoidance offsets the benefits of reducing collisions. Pedestrians, if hit, would be hit at higher speeds leading to a net reduction in pedestrian survivability for collision-minimizing maneuvers. First, this trend is demonstrated and explained using a simplified point-mass model of a vehicle, which is then verified with a higher-fidelity vehicle model as well as experimental maneuvers with an instrumented vehicle. While real accidents involve dozens of important parameters, this research provides a general framework for an under-recognized effect under certain common conditions. The implication of this finding suggests that future research in pedestrian avoidance should consider fatality minimization as an alternative objective to collision minimization.

Deep-Channel uses deep neural networks to detect single-molecule events from patch-clamp data.

Single-molecule research techniques such as patch-clamp electrophysiology deliver unique biological insight by capturing the movement of individual proteins in real time, unobscured by whole-cell ensemble averaging. The critical first step in analysis is event detection, so called "idealisation", where noisy raw data are turned into discrete records of protein movement. To date there have been practical limitations in patch-clamp data idealisation; high quality idealisation is typically laborious and becomes infeasible and subjective with complex biological data containing many distinct native single-ion channel proteins gating simultaneously. Here, we show a deep learning model based on convolutional neural networks and long short-term memory architecture can automatically idealise complex single molecule activity more accurately and faster than traditional methods. There are no parameters to set; baseline, channel amplitude or numbers of channels for example. We believe this approach could revolutionise the unsupervised automatic detection of single-molecule transition events in the future.

Kir6.2-D323 and SUR2A-Q1336: an intersubunit interaction pairing for allosteric information transfer in the KATP channel complex.

ATP-sensitive potassium (KATP) channels are widely expressed and play key roles in many tissues by coupling metabolic state to membrane excitability. The SUR subunits confer drug and enhanced nucleotide sensitivity to the pore-forming Kir6 subunit, and so information transfer between the subunits must occur. In our previous study, we identified an electrostatic interaction between Kir6 and SUR2 subunits that was key for allosteric information transfer between the regulatory and pore-forming subunit. In this study, we demonstrate a second putative interaction between Kir6.2-D323 and SUR2A-Q1336 using patch clamp electrophysiological recording, where charge swap mutation of the residues on either side of the potential interaction compromise normal channel function. The Kir6.2-D323K mutation gave rise to a constitutively active, glibenclamide and ATP-insensitive KATP complex, further confirming the importance of information transfer between the Kir6 and SUR2 subunits. Sensitivity to modulators was restored when Kir6.2-D323K was co-expressed with a reciprocal charge swap mutant, SUR-Q1336E. Importantly, equivalent interactions have been identified in both Kir6.1 and Kir6.2 suggesting this is a second important interaction between Kir6 and the proximal C terminus of SUR.

A novel form of glycolytic metabolism-dependent cardioprotection revealed by PKCα and ß inhibition.

KEY POINTS: Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient. Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non-diabetics. This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition. If PKCα/ß isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage. Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia. ABSTRACT: Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/ß (PKCα/ß) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/ß activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat-peptide-linked PKCαß inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia-sensitive leak current, and time to Kir 6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/ß inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole-heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαß inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαß inhibition in ACS associated with hyperglycaemia.

Shifting habitat mosaics and fish production across river basins.

Watersheds are complex mosaics of habitats whose conditions vary across space and time as landscape features filter overriding climate forcing, yet the extent to which the reliability of ecosystem services depends on these dynamics remains unknown. We quantified how shifting habitat mosaics are expressed across a range of spatial scales within a large, free-flowing river, and how they stabilize the production of Pacific salmon that support valuable fisheries. The strontium isotope records of ear stones (otoliths) show that the relative productivity of locations across the river network, as both natal- and juvenile-rearing habitat, varies widely among years and that this variability is expressed across a broad range of spatial scales, ultimately stabilizing the interannual production of fish at the scale of the entire basin.

Isotopes in teeth and a cryptic population of coastal freshwater seals.

Human activities threaten the biodiversity of aquatic mammals across the globe. Conservation of these species hinges on the ability to delineate movements and foraging behaviors of animals, but gaining such insights is hampered by difficulties in tracing individuals over their lives. We determined isotope ratios in teeth (87 Sr/86 Sr, 13 C/12 C, and 18 O/16 O) to examine lifelong movement and resource-use patterns of a unique freshwater population of a wide-ranging pinniped species (harbor seal [Phoca vitulina]) that resides in Iliamna Lake, Alaska (U.S.A.). This population's potentially unique migratory behavior and use of different trophic resources are unknown. The isotope ratios we measured in teeth showed that seals were born in the lake, remained lifelong residents, and relied principally on resources produced from in the lake, even when seasonally abundant and nutrient-dense spawning anadromous fish (i.e., sockeye salmon [Oncorhynchus nerka]) were available in the lake. Our results illustrate how serial isotope records in teeth, particularly 87 Sr/86 Sr ratios, can be used to quantify how coastal mammal populations exploit both freshwater and marine ecosystems. Understanding lifelong patterns of habitat and resource use is essential information when designing effective conservation plans for threatened coastal mammals. We present the Iliamna Lake harbor seals as a unique case study into how isotope records within teeth can help reveal the cryptic ecology of such a population residing in an intact ecosystem. The results also provide critical baseline information for the Kvichak River system, which is facing an uncertain future due to proposed large-scale industrial development and a rapidly changing climate.

Isotopos Dentales y una Población Críptica de Focas Costeras de Agua Dulce Resumen Las actividades humanas amenazan a la diversidad de mamíferos acuáticos en todo el mundo. La conservación de estas especies depende de la habilidad para delinear los movimientos y los comportamientos de búsqueda de alimento de los animales, pero la obtención de dicha información está obstaculizada por las dificultades en el rastreo de individuos a lo largo del transcurso de sus vidas. Determinamos la proporción de isotopos dentales (87 Sr/86 Sr, 13 C/12 C y 18 O/16 O) para examinar el movimiento a lo largo de la vida y los patrones de uso de recursos de una población única de una especie de pinnípedos de agua dulce con una distribución amplia (foca común [Phoca vitulina]), la cual reside en el lago Iliamna, Alaska (E.U.A.). Se desconocen el comportamiento migratorio potencialmente único de esta población y el uso que le dan a los diferentes recursos tróficos. La proporción de isotopos que medimos en los dientes mostró que las focas nacieron en el lago, permanecieron como residentes de toda la vida y dependieron principalmente de los recursos producidos en el lago, incluso cuando estaban disponibles en aquel lugar por razones reproductivas los peces anádromos abundantes estacionalmente y con densidad de nutrientes (es decir, el salmón rojo [Oncorhynchus nerka]). Nuestros resultados ilustran cómo los registros seriales de isotopos dentales, particularmente la proporción 87 Sr/86 Sr, pueden usarse para cuantificar cómo las poblaciones de mamíferos costeros explotan tanto los ecosistemas marinos como los de agua dulce. El entendimiento de los patrones ontogénicos del uso de recursos y de hábitat es esencial cuando se diseñan planes efectivos de conservación para los mamíferos costeros en peligro. Presentamos a las focas comunes del lago Iliamna como un estudio de caso único sobre cómo los registros de isotopos dentales pueden ayudar a revelar la ecología críptica de dicha población que reside en un ecosistema intacto. Los resultados también proporcionan información importante de línea base para el sistema el río Kvichak, el cual está enfrentando un futuro incierto debido a la propuesta de un desarrollo industrial de gran escala y al rápido clima cambiante.

Impact of community respiratory viral infections in urban children with asthma.

BACKGROUND: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. OBJECTIVE: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. METHODS: We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. RESULTS: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. CONCLUSION: Urban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.

Telehealth in radiation oncology at the Townsville Cancer Centre: Service evaluation and patient satisfaction.

PURPOSE: Telehealth (TH) in Radiation Oncology at Townsville Cancer Centre (TCC) was implemented in July 2011 to provide cancer care closer to home to the regional and rural population. The aim of this study was to describe the service use and patient satisfaction. MATERIALS AND METHODS: A retrospective audit of records was conducted for patients treated at TCC between July 2011 and December 2015. Data included patient demographics, diagnosis and treatment. Results of a patient satisfaction survey were summarised through descriptive statistics. RESULTS: A total of 1530 TH consultations were provided to 833 patients. 311 patient charts were audited (615 TH, 650 in-person, 151 phone consultations). Median distance from TCC to satellites was 327.3 km (21.6 to 1130.1). 71% were male and median age was 65 (23-94 years). Cancer diagnoses included prostate (32%), breast (12%) and head and neck (10%). 60% of patients underwent radiation therapy for curative intent, 22% palliative and 18% did not undergo treatment. 106 patients participated in the satisfaction survey (231 patients invited, response rate of 46%), with the overall positive response mainly attributed to advantages in travel and time savings. 54.7% of patients selected TH as their preference for future consultations, 34.9% indicated a mix of TH and in-person consultations, and only 1 patient (0.9%) indicating in-person only. CONCLUSION: TH enables the delivery of radiation oncology consultations to rural and regional patients, with an overall high level of patient satisfaction. Patients welcomed the model for benefits of travel and time savings. Future directions include engaging with specialist, rural medical staff and patients to maximize access.

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children.

BACKGROUND: Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS: Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection. RESULTS: As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1. CONCLUSIONS: In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.