Rapid creation of a website to produce educational and clinical support resources for global use during and beyond the COVID-19 pandemic.

It became clear at the onset of the pandemic that radiography could play an important role in diagnosing and staging COVID-19. The key modality would be mobile chest radiography. However, at the onset of the pandemic, no literature existed to indicate whether or not chest X-ray imaging could be used effectively to diagnose or exclude COVID-19. This article explains how a website was created, at speed, during the initial phase of the COVID-19 pandemic. Containing holistic information, the website helped enable rapid redeployment of radiographers onto the frontline where chest X-ray imaging was needed. It aimed to help train radiographers take (and interpret) chest radiographs in high-risk areas that contained large numbers of COVID-19 patients. Within one year, the website had been used in 157 countries. This article documents the approach taken to create the website and suggestions are made about how, in the future, a rapid approach could be achieved to create other websites - should an international crisis occur again. This paper also outlines how stakeholders and content authors from across the world were brought together and supported to create the website. It goes on to explain the leadership style that was adopted to create the website and why that style was selected. An explanation is offered about the project management approach and how its ingredients relate to a published model. Aside from simply providing a historical account of how the website was created, we hope the narrative offers food for thought on how to respond rapidly during an international crisis to formulate and implement a unified international-level solution which addresses an urgent need.

Beyond A single stimulus: How to leverage the federal government to advance clean energy innovation?

There is a critical need to accelerate and improve the innovation process for clean energy technologies. In order to stem the most-dire effects of the climate crisis, there will need to be increased research, development, demonstration, commercialization, deployment, and adoption of clean energy technologies. The innovation process for energy technologies is especially challenging compared with other technological sectors, and can be strengthened through better use of the unique capabilities of the federal government. Recently, the focus of efforts to enhance clean energy innovation has been on what a stimulus bill and/or single piece of legislation can achieve. However, the federal government possesses numerous other means for strengthening the energy innovation process: (1) taking on a greater quantity of risk in the federal government's RD&D portfolio; (2) extending the federal government's support for clean energy technologies through its purchasing power; (3) drawing on the full scope of the federal government; and (4) putting energy innovation in the context of societal transformations. Insights on how to draw on the federal government's resources to support clean energy innovation through these means are described and discussed with an eye toward applicability and actionable steps.

Benefits and Risks of Intercropping for Crop Resilience and Pest Management.

To combat climate change, farmers must innovate through ecological intensification to boost food production, increase resilience to weather extremes, and shrink the carbon footprint of agriculture. Intercropping (where alternative crops or noncrop plants are integrated with cash crops) can strengthen and stabilize agroecosystems under climate change by improving resource use efficiency, enhancing soil water holding capacity, and increasing the diversity and quality of habitat for beneficial insects that provide pollination services and natural pest control. Despite these benefits, intercropping has yet to be widely adopted due to perceived risks and challenges including decreased crop yield, increased management complexity, a steep learning curve for successful management, and increased susceptibility to pests. Here, we explore the major benefits of intercropping in agricultural systems for pest control and climate resilience reported in 24 meta-analyses, while addressing risks and barriers to implementation. Most studies demonstrate clear benefits of intercropping for weed, pathogen, insect pest control, relative yield, and gross profitability. However, relatively few studies document ecosystem services conferred by intercrops alongside labor costs, which are key to economic sustainability for farmers. In addition to clearer demonstrations of the economic viability of intercropping, farmers also need strong technical and financial support during the adoption process to help them troubleshoot the site-specific complexities and challenges of managing polycultures. Ecological intensification of agriculture requires a more strategic approach than simplified production systems and is not without risks and challenges. Calibrating incentive programs to reduce financial burdens of risk for farmers could promote more widespread adoption of intercropping.

Modeling the evolution of herbicide resistance in weed species with a complex life cycle.

A growing number of weed species have evolved resistance to herbicides in recent years, which causes an immense financial burden to farmers. An increasingly popular method of weed control is the adoption of crops that are resistant to specific herbicides, which allows farmers to apply the herbicide during the growing season without harming the crop. If such crops are planted in the presence of closely related weed species, it is possible that resistance genes could transfer from the crop species to feral populations of the wild species via gene flow and become stably introgressed under ongoing selective pressure by the herbicide. We use a density-dependent matrix model to evaluate the effect of planting such crops on the evolution of herbicide resistance under a range of management scenarios. Our model expands on previous simulation studies by considering weed species with a more complex life cycle (perennial, rhizomatous weed species), studying the effect of environmental variation in herbicide effectiveness, and evaluating the role of common simplifying genetic assumptions on resistance evolution. Our model predictions are qualitatively similar to previous modeling studies using species with a simpler life cycle, which is, crop rotation in combination with rotation of herbicide site of action effectively controls weed populations and slows the evolution of herbicide resistance. We find that ignoring the effect of environmental variation can lead to an over- or under-prediction of the speed of resistance evolution. The effect of environmental variation in herbicide effectiveness depends on the resistance allele frequency in the weed population at the beginning of the simulation. Finally, we find that degree of dominance and ploidy level have a much larger effect on the predicted speed of resistance evolution compared to the rate of gene flow.

A Study of GP Workload and Satisfaction.

Aims In this novel study in the Irish setting, we quantified the number items managed per General Practitioner (GP) consult, how each item is managed, and impact on a GP's job satisfaction. Methods Participating GPs at two surgeries completed a questionnaire - integrated into the practice management software - after each consultation that satisfied the inclusion criteria during a four-week period. Results Due to feasibility constraints, 500 of 857 (58.3%) completed questionnaires were randomly selected for our sample. GPs manage an average of 1.76 items per consultation. Older patients presented with more items. Greater number of presenting items led to less being managed on the day 71% (n=5) for 5 items vs. 95.2% (n= 246) for 1 item, longer consultation duration (mean = 14.63 minutes (4-45) and decreased GP satisfaction, mean 8/10 (2-10). Conclusion Increasing the number of items in a GP consultation has a statistically significant effect on duration of consultation, how each item is managed, and even GP satisfaction.

The occurrence of cardiac abnormalities in canine steroid-responsive meningitis arteritis.

OBJECTIVES: To document the prevalence of cardiac abnormalities in dogs with steroid-responsive meningitis arteritis and to assess resolution of these abnormalities following corticosteroid therapy. MATERIALS AND METHODS: Steroid-responsive meningitis arteritis was diagnosed based on signalment, physical examination findings, complete blood count, biochemistry and CSF analysis. Echocardiography, C-reactive protein and cardiac troponin I were measured in all cases before and 10 to 14 days after commencing corticosteroid therapy. Fibrinogen was also measured in a proportion of dogs. RESULTS: Fourteen dogs were prospectively enrolled. Increased cardiac troponin I was identified in five of 14 dogs and echocardiographic abnormalities were detected in 12 of 14 dogs, including spontaneous echo contrast (12 of 14), mild pericardial effusion (five of 14) and mildly decreased fractional shortening (five of 14). All dogs had increased C-reactive protein and fibrinogen was increased in 11 of 12. Corticosteroid treatment was associated with clinical improvement and normalisation of C-reactive protein in all dogs. The cardiac troponin I levels normalised in four of five and fibrinogen had normalised in all five dogs which were retested. Spontaneous echo contrast improved or completely resolved in 12 of 12 and pericardial effusion resolved in five of five dogs. Fractional shortening normalised in two of five dogs. CLINICAL SIGNIFICANCE: Cardiac changes are common in dogs with steroid-responsive meningitis arteritis and most resolve with therapy. Further investigation into the cause and significance of these changes is necessary in determining whether antithrombotic therapy or positive inotropic therapy is indicated.

Do the contemporary dietary patterns of children align with national food and nutrient recommendations?

BACKGROUND: Childhood nutrition is important in optimising growth, development and future health. The present study compared dietary intakes of Australian children aged 4-8 years with (i) Australian Guide to Healthy Eating (AGHE) food group recommendations and (ii) age-specific Nutrient Reference Values (NRVs), in addition to (iii) describing food group intakes of children meeting key NRVs. METHODS: Data were obtained from a representative sample of children (n = 789) from the National Nutrition and Physical Activity Survey between May 2011 and June 2012. Parent-reported 24-h recall dietary data were disaggregated into five core food groups, along with energy-dense, nutrient-poor (EDNP) foods, with intakes being compared with AGHE recommendations. Food group intakes were compared for children meeting the NRVs for 10 nutrients used for the development of AGHE food groups. Chi-squared and t-tests were performed to determine differences in food group intakes with P < 0.05 considered statistically significant. RESULTS: Only one child met the recommended daily servings for all AGHE core food groups and none met both core and energy-dense, nutrient-poor (EDNP) food group recommendations. The lowest level of alignment (percentage meeting recommendations) was for vegetables (4.6%) and the highest was for fruit (47.7%). Mean (SD) daily intake of EDNP foods [4.7 (3.2) serves day-1 ] accounted for 38.4% of total energy intakes. Children meeting key NRVs (n = 395) consumed greater daily servings of fruit [2.2 (1.7)], dairy [2.2 (1.2)] and EDNP foods [5.0 (3.4)] compared to the total sample (n = 789). CONCLUSIONS: Significant discrepancies exist between contemporary dietary patterns of Australian children and national recommendations. Future AGHE revisions should incorporate greater diversity of consumption patterns, including sub-categories of EDNP foods.

Assessment of patients' attitudes towards weight loss in an Irish general practice setting.

BACKGROUND: Ireland is on course to become the most obese country in Europe by 2025. A recently published action plan for obesity in Ireland identifies primary care as one of the best places to tackle this issue. AIM: This study aims to assess patients' attitudes towards weight loss management in general practice in Ireland. DESIGN AND SETTING: A descriptive study was conducted at one urban single-handed and one rural group practice in the south west of Ireland. METHOD: The study is a quantitative cross-sectional survey. RESULTS: The response rate was 18.72% in the rural and 22.8% in the urban practice. Thirty-three percent of patients underestimated their BMI. Sixty-four percent of overweight and 39% of obese patients said their general practitioner (GP) had never discussed their weight with them. Eighty-five percent of overweight and 68% of obese patients were never told their weight might be affecting their health. Only 19% of obese patients had been referred to a weight loss service. Eighty-seven percent of respondents felt their GP would be a good person to advise them. The main reasons patients felt that their weight was not addressed include patients themselves only wanting to discuss the issue they came with and they also felt that time pressure was stopping GPs. CONCLUSION: Overweight or obese patients are more likely to underestimate their BMI. GPs are not discussing weight management with patients who would benefit the most. There is a poor referral rate to weight loss services. Patients are happy to discuss their weight with their GP but are aware that time management is an issue in their consultations.

To which countries do European psychiatric trainees want to move to and why?

BACKGROUND: There is a shortage of psychiatrists worldwide. Within Europe, psychiatric trainees can move between countries, which increases the problem in some countries and alleviates it in others. However, little is known about the reasons psychiatric trainees move to another country. METHODS: Survey of psychiatric trainees in 33 European countries, exploring how frequently psychiatric trainees have migrated or want to migrate, their reasons to stay and leave the country, and the countries where they come from and where they move to. A 61-item self-report questionnaire was developed, covering questions about their demographics, experiences of short-term mobility (from 3 months up to 1 year), experiences of long-term migration (of more than 1 year) and their attitudes towards migration. RESULTS: A total of 2281 psychiatric trainees in Europe participated in the survey, of which 72.0% have 'ever' considered to move to a different country in their future, 53.5% were considering it 'now', at the time of the survey, and 13.3% had already moved country. For these immigrant trainees, academic was the main reason they gave to move from their country of origin. For all trainees, the overall main reason for which they would leave was financial (34.4%), especially in those with lower (<500€) incomes (58.1%), whereas in those with higher (>2500€) incomes, personal reasons were paramount (44.5%). CONCLUSIONS: A high number of psychiatric trainees considered moving to another country, and their motivation largely reflects the substantial salary differences. These findings suggest tackling financial conditions and academic opportunities.

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells.

Osteosarcoma tissues and cell lines from patients with differing serum alkaline phosphatase concentrations display minimal differences in gene expression patterns.

Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normal ALP group. Using quantitative PCR (qPCR), differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells.

Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas.

BACKGROUND: A promising therapeutic approach for aggressive B-cell Non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) is to target kinases involved in signal transduction and gene regulation. PIM1/2 serine/threonine kinases are highly expressed in activated B-cell-like DLBCL (ABC-DLBCL) with poor prognosis. In addition, both PIM kinases have a reported synergistic effect with c-MYC in mediating tumour development in several cancers, c-MYC gene being translocated to one of the immunoglobulin loci in nearly all BLs. METHODS: For these reasons, we tested the efficiency of several PIM kinase inhibitors (AZD1208, SMI4a, PIM1/2 inhibitor VI and Quercetagetin) in preventing proliferation of aggressive NHL-derived cell lines and compared their efficiency with PIM1 and/or PIM2 knockdown. RESULTS: We observed that most of the anti-proliferative potential of these inhibitors in NHL was due to an off-target effect. Interestingly, we present evidence of a kinase-independent function of PIM2 in regulating cell cycle. Moreover, combining AZD1208 treatment and PIM2 knockdown additively repressed cell proliferation. CONCLUSION: Taken together, this study suggests that at least a part of PIM1/2 oncogenic potential could be independent of their kinase activity, justifying the limited anti-tumorigenic outcome of PIM-kinase inhibitors in NHL.

Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differences in vitro.

Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumour size, presence of metastatic disease and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behaviour of osteosarcoma cells differ based on serum ALP concentration. Here, we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion or chemosensitivity between cell lines associated with normal or increased serum ALP concentration.

Treatment of children over the age of one year with unresectable localised neuroblastoma without MYCN amplification: results of the SIOPEN study.

BACKGROUND: In children older than 1 year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery. PATIENTS AND METHODS: In the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin-Etoposide and Vincristin-Cyclophosphamide-Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%. RESULTS: Out of 191 registered children, 160 were evaluable. There were 62.5% older than 18 months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18 months or with favourable histology. CONCLUSION: This strategy provides encouraging results in children older than 1 year or 12 months with localised unresectable NB without MYCN amplification. However, in children older than 18 months and with unfavourable histology, additional treatment is recommended.

Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection.

A single dose of florfenicol (Nuflor(®)) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross-over design, and 28-day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long-term effects. Maximum plasma florfenicol concentrations (C(max), measured via high-performance liquid chromatography) were achieved rapidly, leading to a higher C(max) of 4.31±3.03 µg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (C(max): 1.95±0.94 µg/mL). Multiple s.c. dosing at 48 h intervals achieved a C(max) of 4.48±1.28 µg/mL at steady state. The area under the curve and terminal elimination half-lives were 51.83±11.72 µg/mL·h and 17.59±11.69 h after single 2 mg/kg i.m. dose, as well as 99.78±23.58 µg/mL·h and 99.67±59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL, P<0.0001), globulin (2.76 vs. 2.16 g/dL, P<0.0003), albumin (3.61 vs. 3.48 g/dL, P=0.0038), white blood cell count (11.89 vs. 9.66×10(3)/µL, P<0.044), and hematocrit (27.25 vs. 24.88%, P<0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.

Characterization of ß-catenin expression in canine osteosarcoma.

Osteosarcoma (OSA) is the most frequently occurring malignant primary bone tumour in dogs and children and arises from cells of the osteoblast lineage. Inappropriate Wnt signalling activity has been implicated in human OSA. Altered expression of ß-catenin, an integral member of the Wnt signalling pathway, has been associated with numerous human cancers, including OSA. In this study, 30 of the 37 primary canine OSA tissues and 2 of the 3 metastatic OSAs were positive for ß-catenin expression as determined by immunohistochemistry, whereas 2 normal bones stained negative for ß-catenin. No mutations were identified in exon 3 of ß-catenin in the three OSA cases in which DNA sequencing was performed. Finally, there was no relationship between ß-catenin expression and overall survival time or disease-free interval. Our results indicate ß-catenin is frequently expressed within the cytoplasm of neoplastic cells in canine OSA but contains no detectable mutations in exon 3, similar to human OSA.