Jupiter's X-Ray and UV Dark Polar Region.

We present 14 simultaneous Chandra X-ray Observatory (CXO)-Hubble Space Telescope (HST) observations of Jupiter's Northern X-ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X-ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X-ray photons. For all 14 observations, the low level of X-ray emission from the DPR is consistent (within 2-standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X-ray-bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X-ray signature.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

Reducing long acting antipsychotic injection dosage frequency: A pilot study in a community mental health team.

BACKGROUND: Antipsychotic long acting injections (LAI) allow a range of dosage intervals to be administered. Short intervals can be inconvenient for patients and staff. There are few clinical reasons for using them yet this is common practice. AIMS: This study aimed to examine the feasibility of reducing LAI frequency with service user consent. METHODS: The study took place in a community mental health team in the north of England. A specialist mental health pharmacist reviewed records of all service users on LAI and drew up an action plan. Each service user then met with the consultant psychiatrist for medication review. RESULT: Nineteen out of thirty service users on LAI had intervals less than the maximum licensed. The frequency was reduced in eight cases. After 6 months follow-up, there was no deterioration in symptoms. In nine cases, antipsychotic doses were also reduced as a result of the review. CONCLUSION: Where a service user is prescribed a LAI with a short dosage interval consideration should be given to increase the interval. This can free up service user and staff time. A medication focused review can also lead to other benefits such as dosage reduction.

Direct observation of muonium reacting with uncapped gold nanoparticles in porous silica and nature of the final state.

We report the reaction of muonium (Mu = [µ+e-]), a light isotopic analog of hydrogen, with uncapped gold nanoparticles embedded in mesoporous silica. Using the radio-frequency muon spin rotation (RF-µSR) technique, we directly observe and characterize the resulting final state on the nanoparticle surface, showing conclusively its diamagnetic nature. The magnetic environment experienced by the reacted muons is only weakly perturbed compared to that of muons in a silica reference, consistent with the surface of the gold nanoparticles being metallic and non-magnetic. We demonstrate the potential of RF-µSR for the investigation of the surface properties of nanoparticles and show the feasibility of Knight shift measurements of muons on metal surfaces.

Performance comparison of two Olympus InnovX handheld x-ray analyzers for feasibility of measuring arsenic in skin in vivo - Alpha and Delta models.

The Figure-Of-Merit (FOM) performance, a combination of detection limit and dose, is compared between two generations of handheld X-Ray Fluorescence (XRF) spectrometers for the feasibility of in vivo XRF measurement of arsenic (As) in skin. The Olympus InnovX Delta model analyzer (40 kVp using either 37 or 17µA) was found to show improvements in Minimum Detection Limit (MDL) using arsenic As-doped skin calibration phantoms with bulk tissue backing, when compared to the first generation InnovX Alpha model (40kVp, 20µA) in 120s measurements. Differences between two different definitions of MDL are discussed. On the Delta system, an MDL of (0.462±0.002) µg/g As was found in phantoms, with a nylon backing behind to mimic bulk tissue behind skin. The equivalent and effective doses were found to be (10±2) mSv and ~7×10-3µSv respectively for the Alpha and (15±4) mSv and ~8×10-3µSv respectively for the Delta system in 120s exposures. Combining MDL and effective dose, a lower (better) FOM was found for the Delta, (1.7±0.4) ppm mSv1/2, compared to (4.4±0.5) ppm mSv1/2 for the Alpha model system. The Delta analyzer demonstrates improved overall system performance for a rapid 2-min measurement in As skin phantoms, such that it can be considered for use in populations exposed to arsenic.

Age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto.

OBJECTIVE: To study the age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto. APPROACH: A 109Cd K x-ray fluorescence (KXRF) measurement system was used from 2009 to 2011 in a study that measured the bone lead (Pb) concentration of 263 environmentally exposed individuals residing in Toronto, Ontario, Canada. Tibia (cortical bone) and calcaneus (trabecular bone) lead contents were measured in 134 males and 129 females between 1 and 82 years of age. Whole blood Pb concentration was measured by TIMS (thermal ionization mass spectrometer). Tibia (Ti) and calcaneus (Cal) Pb were examined versus the age of participants, taking into account uncertainties in bone Pb measurement values. MAIN RESULTS: No significant sex differences were observed in any of the age categories. Participants older than 50 years of age demonstrated the highest concentrations of Pb in their blood, tibia, and calcaneus bones. SIGNIFICANCE: In most of the previous publications, uncertainty was not considered in the regression model of bone Pb and age. However, in this paper, we adjusted the bone Pb values for the uncertainty level. This had a significant influence in regression models of bone Pb and thus we recommend that uncertainty be considered in future studies.

Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus.

The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)(0-12) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therapeutic drug monitoring of MPA. On the day of the test, 10 specimens were collected, analyzed, and MPA AUC(0-12) was calculated. Using step-wise regression analysis, LSS equations were developed. Using bootstrap validation, the predictive performance was calculated. The measured mean (standard deviation) for the trough concentration and AUC(0-12) were 2.55 (1.57) µg/ml and 62.6 (21.67) mg.h/L, respectively. The range of trough concentrations and AUC(0-12) were 0.7-5.54 µg/ml and 22.1-104.8 mg.h/L, respectively. The interindividual variability (%CV) for dose normalized AUC(0-12) and dose normalized Ctrough was 46.5% and 61.1%, respectively. The correlation between the concentrations at the different time points and MPA AUC(0-12) ranged from 0.05 (1.5 h) to 0.56 (4 h). Two LSS equations that included 4 or 5 time points up to 3 h were developed and validated. The 4 point LSS had a correlation (R2) of 0.88 and the 5 point LSS an R2 of 0.87. With respect to the 4 point and 5 point MPA LSS AUC(0-12), the bias was 1.92% and 1.96%, respectively, and the imprecision was 11.24% and 11.28%, respectively. A 4 point LSS which concludes within 3 h after the administration of the MMF dose was developed and validated, to determine the MPA AUC(0-12) in children with SLE.

Communication: Chemisorption of muonium on gold nanoparticles: A sensitive new probe of surface magnetism and reactivity.

Chemisorption of muonium onto the surface of gold nanoparticles has been observed. Muonium (µ+e-), a light hydrogen-like atom, reacts chemically with uncapped 7 nm gold nanoparticles embedded in mesoporous silica (SBA-15) with a strong temperature-dependent rate. The addition rate is fast enough to allow coherent spin transfer into a diamagnetic muon state on the nanoparticle surface. The muon is well established as a sensitive probe of static or slowly fluctuating magnetic fields in bulk matter. These results represent the first muon spin rotation signal on a nanoparticle surface or any metallic surface. Only weak magnetic effects are seen on the surface of these Au nanoparticles consistent with Pauli paramagnetism.

Single nucleotide variant discovery of highly inbred Leghorn and Fayoumi chicken breeds using pooled whole genome resequencing data reveals insights into phenotype differences.

BACKGROUND: Analyses of sequence variants of two distinct and highly inbred chicken lines allowed characterization of genomic variation that may be associated with phenotypic differences between breeds. These lines were the Leghorn, the major contributing breed to commercial white-egg production lines, and the Fayoumi, representative of an outbred indigenous and robust breed. Unique within- and between-line genetic diversity was used to define the genetic differences of the two breeds through the use of variant discovery and functional annotation. RESULTS: Downstream fixation test (F ST ) analysis and subsequent gene ontology (GO) enrichment analysis elucidated major differences between the two lines. The genes with high F ST values for both breeds were used to identify enriched gene ontology terms. Over-enriched GO annotations were uncovered for functions indicative of breed-related traits of pathogen resistance and reproductive ability for Fayoumi and Leghorn, respectively. CONCLUSIONS: Variant analysis elucidated GO functions indicative of breed-predominant phenotypes related to genomic variation in the lines, showing a possible link between the genetic variants and breed traits.

Impact of Insect Management on Population Dynamics and Insecticide Resistance of Tarnished Plant Bug (Hemiptera: Miridae).

While transgenic plants targeting lepidopteran and coleopteran insects have been available for almost 20 yr, there are no transgenic crops that target hemipteran insects such as tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), though at least one company lists potential products in advanced stages of development. A resistance management model for the U.S. Mid-South was developed to aid in resistance risk assessments for transgenic crops targeting L. lineolaris, and validated against the prior case of pyrethroid resistance in this insect. The model predicted that resistance to a pyrethroid would evolve in 17.6-21.0 yr (depending on the initial resistance allele frequency), which was close to the 15-20 years observed in the field. Due to uncertainty in female fecundity, we varied fecundity from 3 eggs/female/day to 12 eggs/female/day. Sprays were applied based on action thresholds, and increasing fecundity therefore increased the number of sprays applied per year and decreased durability. We also varied the action threshold in cotton (Gossypium hirsutum L.) fields (the population levels at which sprays were applied) from 17,600/ha to as low as 1,100/ha. Lowering the threshold increased the number of sprays applied, but also increased durability of the pesticide. Removing the noncotton host refuge present at the same time as cotton changed the relationship so that increasing the action threshold increased durability. The impact of insect resistance management on action threshold cost estimates will vary depending on the landscape, and cannot be assumed to always move the economic injury level in the same direction.

Host Responses to Biofilm.

From birth to death the human host immune system interacts with bacterial cells. Biofilms are communities of microbes embedded in matrices composed of extracellular polymeric substance (EPS), and have been implicated in both the healthy microbiome and disease states. The immune system recognizes many different bacterial patterns, molecules, and antigens, but these components can be camouflaged in the biofilm mode of growth. Instead, immune cells come into contact with components of the EPS matrix, a diverse, hydrated mixture of extracellular DNA (bacterial and host), proteins, polysaccharides, and lipids. As bacterial cells transition from planktonic to biofilm-associated they produce small molecules, which can increase inflammation, induce cell death, and even cause necrosis. To survive, invading bacteria must overcome the epithelial barrier, host microbiome, complement, and a variety of leukocytes. If bacteria can evade these initial cell populations they have an increased chance at surviving and causing ongoing disease in the host. Planktonic cells are readily cleared, but biofilms reduce the effectiveness of both polymorphonuclear neutrophils and macrophages. In addition, in the presence of these cells, biofilm formation is actively enhanced, and components of host immune cells are assimilated into the EPS matrix. While pathogenic biofilms contribute to states of chronic inflammation, probiotic Lactobacillus biofilms cause a negligible immune response and, in states of inflammation, exhibit robust antiinflammatory properties. These probiotic biofilms colonize and protect the gut and vagina, and have been implicated in improved healing of damaged skin. Overall, biofilms stimulate a unique immune response that we are only beginning to understand.

Is the onset of influenza in the community age-related?

We studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. Virus detections [A(H3N2), B, A(H1N1)] and clinical incidence of influenza-like illness (ILI) in 12·3 million person-years in the long-running Royal College of General Practitioners-linked clinical-virological surveillance programme in England & Wales were examined. The number of days between symptom onset and the all-age peak ILI incidence were compared by age group for each influenza type/subtype. We found that virus detection and ILI incidence increase, peak and decrease were in unison. The mean interval between symptom onset to peak ILI incidence in virus detections (all ages) was: A(H3N2) 20·5 [95% confidence interval (CI) 19·7-21·6] days; B, 18·8 (95% CI 15·8·0-21·7) days; and A(H1N1) 17·0 (95% CI 15·6-18·4) days. Differences by age group were examined using the Kruskal-Wallis test. For A(H3N2) and A(H1N1) viruses the interval was similar in each age group. For influenza B there were highly significant differences by age group (P = 0·0001). Clinical incidence rates of ILI reported in the 8 weeks preceding the period of influenza virus activity were used to estimate a baseline incidence and threshold value (upper 95% CI of estimate) which was used as a marker of epidemic progress. Differences between the age groups in the week in which the threshold was reached were small and not localized to any age group. In conclusion we found no evidence to suggest that influenza A(H3N2) and A(H1N1) occurs in the community in one age group before another. For influenza B, virus detection was earlier in children aged 5-14 years than in persons aged ⩾25 years.

Genomic analysis of Ugandan and Rwandan chicken ecotypes using a 600 k genotyping array.

BACKGROUND: Indigenous populations of animals have developed unique adaptations to their local environments, which may include factors such as response to thermal stress, drought, pathogens and suboptimal nutrition. The survival and subsequent evolution within these local environments can be the result of both natural and artificial selection driving the acquisition of favorable traits, which over time leave genomic signatures in a population. This study's goals are to characterize genomic diversity and identify selection signatures in chickens from equatorial Africa to identify genomic regions that may confer adaptive advantages of these ecotypes to their environments. RESULTS: Indigenous chickens from Uganda (n = 72) and Rwanda (n = 100), plus Kuroilers (n = 24, an Indian breed imported to Africa), were genotyped using the Axiom® 600 k Chicken Genotyping Array. Indigenous ecotypes were defined based upon location of sampling within Africa. The results revealed the presence of admixture among the Ugandan, Rwandan, and Kuroiler populations. Genes within runs of homozygosity consensus regions are linked to gene ontology (GO) terms related to lipid metabolism, immune functions and stress-mediated responses (FDR < 0.15). The genes within regions of signatures of selection are enriched for GO terms related to health and oxidative stress processes. Key genes in these regions had anti-oxidant, apoptosis, and inflammation functions. CONCLUSIONS: The study suggests that these populations have alleles under selective pressure from their environment, which may aid in adaptation to harsh environments. The correspondence in gene ontology terms connected to stress-mediated processes across the populations could be related to the similarity of environments or an artifact of the detected admixture.

Influenza-attributable burden in United Kingdom primary care.

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods.

In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity. A non-invasive measurement of both elements could therefore be of potential interest. The main aim of this current study was to evaluate and compare the performance of an upgraded portable XRF system and an advanced version of the benchtop XRF system for both selenium and arsenic. This evaluation was performed in terms of arsenic and selenium Kα detection limits for a 4W gold anode Olympus InnovX Delta portable analyzer (40 kVp) in polyester resin skin-mimicking phantoms. Unlike the polychromatic source earlier reported in the literature, the benchtop tube-based technique involves monochromatic excitation (25 W silver anode, manufactured by x-ray optics, XOS) and a higher throughput detector type. Use of a single exciting energy allows for a lower in vivo dose delivered and superior signal-noise ratio. For the portable XRF method, arsenic and selenium minimum detection limits (MDLs) of 0.59 ± 0.03 ppm and 0.75 ± 0.02 ppm respectively were found for 1 min measurement times. The MDLs for arsenic and selenium using the benchtop system were found to be 0.35 ± 0.01 ppm and 0.670 ± 0.004 ppm respectively for 30 min measurement times. In terms of a figure of merit (FOM), allowing for dose as well as MDL, the benchtop system was found to be superior for arsenic and the two systems were equivalent, within error, for selenium. We shall discuss the performance and possible improvements of each system, their ease of use and potential for field application.

Comparisons of Lygus lineolaris (Hemiptera: Miridae) Populations from Two Distinct Geographical Regions of Mississippi.

The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), is a major pest of cotton (Gossypium hirsutum L.) in the state of Mississippi. Economic data indicate that L. lineolaris is a more serious pest of cotton in the Delta region of Mississippi than in the Hills region; however, little data exist comparing the two populations. Two experiments were undertaken to compare L. lineolaris from these two geographically distinct regions. In the first experiment, colonies of L. lineolaris from each region were reared in the laboratory under controlled conditions and measurements of development time, survivorship, fecundity, and hatch rate were compared. The geographic region of origin had no effect on any of the variables measured; however, the diet used for rearing had a significant effect on all variables except hatch rate. In the second experiment, part of the cox1 gene of the L. lineolaris mitochondrial genome was compared between the two populations to examine possible genetic differences between L. lineolaris from the two regions of Mississippi. Data revealed two cox1 clades in the Delta region and only one cox1 clade in the Hills region. Taken together, the data do not explain the reason for the differences in the severity of damage to cotton in the two regions.

Self-sampling for community respiratory illness: a new tool for national virological surveillance.

This report aims to evaluate the usefulness of self-sampling as an approach for future national surveillance of emerging respiratory infections by comparing virological data from two parallel surveillance schemes in England. Nasal swabs were obtained via self-administered sampling from consenting adults (≥ 16 years-old) with influenza symptoms who had contacted the National Pandemic Flu Service (NPFS) health line during the 2009 influenza pandemic. Equivalent samples submitted by sentinel general practitioners participating in the national influenza surveillance scheme run jointly by the Royal College of General Practitioners (RCGP) and Health Protection Agency were also obtained. When comparable samples were analysed there was no significant difference in results obtained from self-sampling and clinician-led sampling schemes. These results demonstrate that self-sampling can be applied in a responsive and flexible manner, to supplement sentinel clinician-based sampling, to achieve a wide spread and geographically representative way of assessing community transmission of a known organism.

Harmonizing influenza primary-care surveillance in the United Kingdom: piloting two methods to assess the timing and intensity of the seasonal epidemic across several general practice-based surveillance schemes.

General Practitioner consultation rates for influenza-like illness (ILI) are monitored through several geographically distinct schemes in the UK, providing early warning to government and health services of community circulation and intensity of activity each winter. Following on from the 2009 pandemic, there has been a harmonization initiative to allow comparison across the distinct existing surveillance schemes each season. The moving epidemic method (MEM), proposed by the European Centre for Disease Prevention and Control for standardizing reporting of ILI rates, was piloted in 2011/12 and 2012/13 along with the previously proposed UK method of empirical percentiles. The MEM resulted in thresholds that were lower than traditional thresholds but more appropriate as indicators of the start of influenza virus circulation. The intensity of the influenza season assessed with the MEM was similar to that reported through the percentile approach. The MEM pre-epidemic threshold has now been adopted for reporting by each country of the UK. Further work will continue to assess intensity of activity and apply standardized methods to other influenza-related data sources.

Big Data Usage Patterns in the Health Care Domain: A Use Case Driven Approach Applied to the Assessment of Vaccination Benefits and Risks. Contribution of the IMIA Primary Healthcare Working Group.

BACKGROUND: Generally benefits and risks of vaccines can be determined from studies carried out as part of regulatory compliance, followed by surveillance of routine data; however there are some rarer and more long term events that require new methods. Big data generated by increasingly affordable personalised computing, and from pervasive computing devices is rapidly growing and low cost, high volume, cloud computing makes the processing of these data inexpensive. OBJECTIVE: To describe how big data and related analytical methods might be applied to assess the benefits and risks of vaccines. METHOD: We reviewed the literature on the use of big data to improve health, applied to generic vaccine use cases, that illustrate benefits and risks of vaccination. We defined a use case as the interaction between a user and an information system to achieve a goal. We used flu vaccination and pre-school childhood immunisation as exemplars. RESULTS: We reviewed three big data use cases relevant to assessing vaccine benefits and risks: (i) Big data processing using crowdsourcing, distributed big data processing, and predictive analytics, (ii) Data integration from heterogeneous big data sources, e.g. the increasing range of devices in the "internet of things", and (iii) Real-time monitoring for the direct monitoring of epidemics as well as vaccine effects via social media and other data sources. CONCLUSIONS: Big data raises new ethical dilemmas, though its analysis methods can bring complementary real-time capabilities for monitoring epidemics and assessing vaccine benefit-risk balance.

Effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2012/13 end of season results.

The effectiveness of the 2012/13 trivalent seasonal influenza vaccine (TIV) was assessed using a test-negative case-control study of patients consulting primary care with influenza-like illness in the United Kingdom. Strain characterisation was undertaken on selected isolates. Vaccine effectiveness (VE) against confirmed influenza A(H3N2), A(H1N1) and B virus infection, adjusted for age, sex, surveillance scheme (i.e. setting) and month of sample collection was 26% (95% confidence interval (CI): -4 to 48), 73% (95% CI: 37 to 89) and 51% (95% CI: 34 to 63) respectively. There was an indication, although not significant, that VE declined by time since vaccination for influenza A(H3N2) (VE 50% within three months, 2% after three months, p=0.25). For influenza A(H3N2) this is the second season of low VE, contributing to the World Health Organization (WHO) recommendation that the 2013/14 influenza vaccine strain composition be changed to an A(H3N2) virus antigenically like cell-propagated prototype 2012/13 vaccine strain (A/Victoria/361/2011). The lower VE seen for type B is consistent with antigenic drift away from the 2012/13 vaccine strain. The majority of influenza B viruses analysed belong to the genetic clade 2 and were antigenically distinguishable from the 2012/13 vaccine virus B/Wisconsin/1/2010 clade 3. These findings supported the change to the WHO recommended influenza B vaccine component for 2013/14.