There have been recent calls for Human Factors and Ergonomics (HFE) to expand its reach and focus to address larger scale societal and global issues. An area of growing awareness is the issue of the ...gender data gap, whereby women are under-represented in research data, leading to inequitable outcomes when research findings are used to design real world technologies, products, environments, processes, and policies. The aim of this paper is to showcase how structured HFE methods can be used to address the gender data gap. We applied the Sociotechnical Systems Design Toolkit which involved using causal loop diagrams and abstraction hierarchy modelling from Cognitive Work Analysis to understand the system in which the issue occurs and key pain points, followed by the application of the Design with Intent Toolkit to generate design ideas. A total of 43 ideas were developed that could be implemented by universities to address the research data gap. The application demonstrates the utility of HFE methods in tackling complex issues and offers an opportunity for the HFE community to reflect upon the importance of gender sensitive research practices and gender equity more broadly.
•The gender data gap is a growing area of awareness within the discipline.•The Sociotechnical Systems Design Toolkit was applied.•43 interventions that could be implemented by universities identified.•Prompts reflection on importance of gender sensitive research practices.
Fifteen years ago subterranean clover (
Trifolium subterraneum) and annual medics (
Medicago spp.) dominated annual pasture legume sowings in southern Australia, while limited pasture legume options ...existed for cropping areas of subtropical Australia. Since then a number of sustainability and economic challenges to existing farming systems have emerged, exposing shortcomings in these species and the lack of legume biodiversity. Public breeding institutions have responded to these challenges by developing 58 new annual and short-lived perennial pasture legumes with adaptation to both existing and new farming systems. This has involved commercialisation of new species and overcoming deficiencies in traditional species. Traits incorporated in legumes of Mediterranean Basin origin for the Mediterranean, temperate and southern subtropical climates of Australia include deeper root systems, protection from false breaks (germination-inducing rainfall events followed by death from drought), a range of hardseed levels, acid-soil tolerant root nodule symbioses, tolerance to pests and diseases and provision of lower cost seed through ease of seed harvesting and processing. Ten new species, French serradella (
Ornithopus sativus), biserrula (
Biserrula pelecinus), sulla (
Hedysarum coronarium), gland (
Trifolium glanduliferum), arrowleaf (
Trifolium vesiculosum), eastern star (
Trifolium dasyurum) and crimson (
Trifolium incarnatum) clovers and sphere (
Medicago sphaerocarpos), button (
Medicago orbicularis) and hybrid disc (
Medicago tornata
×
Medicago littoralis) medics have been commercialised. Improved cultivars have also been developed of subterranean (
T. subterraneum), balansa (
Trifolium michelianum), rose (
Trifolium hirtum), Persian (
Trifolium resupinatum) and purple (
Trifolium purpureum) clovers, burr (
Medicago polymorpha), strand (
M. littoralis), snail (
Medicago scutellata) and barrel (
Medicago truncatula) medics and yellow serradella (
Ornithopus compressus). New tropical legumes for pasture phases in subtropical cropping areas include butterfly pea (
Clitoria ternatea), burgundy bean (
Macroptilium bracteatum) and perennial lablab (
Lablab purpureus). Other species and cultivars of Mediterranean species are likely to be released soon. The contributions of genetic resources, rhizobiology, pasture ecology and agronomy, plant pathology, entomology, plant chemistry and animal science have been paramount to this success. A farmer survey in Western Australia has shown widespread adoption of the new pasture legumes, while adoption of new tropical legumes has also been high in cropping areas of the subtropics. This trend is likely to increase due to the increasing cost of inorganic nitrogen, the need to combat herbicide-resistant crop weeds and improved livestock prices. Mixtures of these legumes allows for more robust pastures buffered against variable seasons, soils, pests, diseases and management decisions. This paper discusses development of the new pasture legumes, their potential use and deficiencies in the current suite.
The goal of this study was to characterize the agonist pharmacology of human 5‐HT2A, 5‐HT2B and 5‐HT2C (VSV) receptors expressed in CHO‐K1 (Chinese hamster ovary) cells.
We used a fluorometric ...imaging plate reader (FLIPR) which allows rapid detection of rises in intracellular calcium levels upon the addition of agonists.
Stimulation of all three receptors by 5‐HT caused a robust concentration dependent increase in intracellular calcium levels. No such effect was observed from non‐transfected control CHO‐K1 cells.
The rank order of potency of agonists at the different receptor subtypes varied. Tryptamines, BW‐723C86, d‐norfenfluramine, Ro 60‐0175 and LSD exhibited the following rank order of potency; 5‐HT2B>5‐HT2C>5‐HT2A. Piperazines such as m‐Chlorophenylpiperazine (mCPP), ORG‐12962, MK‐212 and also ORG‐37684 exhibited a rank order of potency of 5‐HT2C>5‐HT2B>5‐HT2A. The phenylisopropylamines DOI and DOB had a rank order of 5‐HT2A>5‐HT2B>5‐HT2C.
Many agonists tested had partial agonist actions when compared to 5‐HT, and a wide range of relative efficacies were exhibited, which was cell line dependent. For example, mCPP had a relative efficacy of 65% at 5‐HT2C receptors but <25% at either 5‐HT2A or 5‐HT2B receptors.
Interpretation of literature values of functional assays using different cell lines, different receptor expression levels and different receptor isoforms, is complex. Species differences and the previous use of antagonist radioligands to characterize agonist potency in binding assays emphasizes the importance of studying agonists in the same experiment using the same assay conditions and parental cell lines.
British Journal of Pharmacology (1999) 128, 13–20; doi:10.1038/sj.bjp.0702751
We have characterised the proteolytic cleavage events responsible for the shedding of triggering receptor expressed on myeloid cells 2 (TREM2) from primary cultures of human macrophages, murine ...microglia and TREM2‐expressing human embryonic kidney (HEK293) cells. In all cell types, a soluble 17 kDa N‐terminal cleavage fragment was shed into the conditioned media in a constitutive process that is inhibited by G1254023X and metalloprotease inhibitors and siRNA targeting ADAM10. Inhibitors of serine proteases and matrix metalloproteinases 2/9, and ADAM17 siRNA did not block TREM2 shedding. Peptidomimetic protease inhibitors highlighted a possible cleavage site, and mass spectrometry confirmed that shedding occurred predominantly at the H157‐S158 peptide bond for both wild‐type and H157Y human TREM2 and for the wild‐type murine orthologue. Crucially, we also show that the Alzheimer's disease‐associated H157Y TREM2 variant was shed more rapidly than wild type from HEK293 cells, possibly by a novel, batimastat‐ and ADAM10‐siRNA‐independent, sheddase activity. These insights offer new therapeutic targets for modulating the innate immune response in Alzheimer's and other neurological diseases.
Synopsis
Sequence variation in the microglial receptor protein TREM2 is linked to risk for Alzheimer's disease. The disease‐linked H157Y variant of TREM2 is found to affect the sheddase site and accelerates proteolytic loss of TREM2 from the cell surface.
TREM2 was shed rapidly from primary macrophages and microglia under basal conditions.
The sheddase site was identified using peptidomimetic inhibitors and mass spectrometry.
The Alzheimer's disease‐linked H157Y TREM2 sheddase‐cleavage‐site variant was shed more rapidly than wild type.
For both wild type and variant TREM2 the major sheddase was ADAM10, however an additional proteolytic activity might be recruited by the H157Y variant.
The protection of TREM2 from proteolysis might represent a novel therapeutic approach.
Sequence variation in the microglial receptor protein TREM2 is linked to risk for Alzheimer's disease. The disease‐linked H157Y variant of TREM2 is found to affect the sheddase site and accelerates proteolytic loss of TREM2 from the cell surface.
Data and methods Analysis of the large-scale circulation in the extratropics is based on a 39-yr time series (1958-96) of 500-hPa geopotential heights (H500) and 300-hPa meridional wind components ...(V300) from the National Centers for Environmental Prediction-National Center for Atmospheric Research (NCEP-NCAR) reanalysis project (Kalnay et al. 1996). Based on the above argument, the region of strong low-frequency circulation variability over the SE Pacific may be taken in part to reflect the mean pattern of variation over a large ensemble of such high-frequency Rossby wave passages, forced by continually varying tropical convection. ...as stated in the introduction, the modulation of tropical convection by the ENSO cycle leads to a somewhat predictable modulation in the ensemble of SE Pacific blocking events over a season.
In the absence of widespread access to individualized laboratory monitoring, which forms an integral part of HIV patient management in resource-rich settings, the roll-out of highly active ...antiretroviral therapy (HAART) in resource-limited settings has adopted a public health approach based on standard HAART protocols and clinical/immunological definitions of therapy failure. The cost-effectiveness of HIV-1 viral load monitoring at the individual level in such settings has been debated, and questions remain over the long-term and population-level impact of managing HAART without it. Computational models that accurately predict virological response to HAART using baseline data including CD4 count, viral load and genotypic resistance profile, as developed by the Resistance Database Initiative, have significant potential as an aid to treatment selection and optimization. Recently developed models have shown good predictive performance without the need for genotypic data, with viral load emerging as by far the most important variable. This finding provides further, indirect support for the use of viral load monitoring for the long-term optimization of HAART in resource-limited settings.
We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia.
A total of 809 patients with essential thrombocythemia who were at high risk for ...vascular events received low-dose aspirin plus either anagrelide or hydroxyurea. The composite primary end point was the actuarial risk of arterial thrombosis (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, or peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis, splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death from thrombotic or hemorrhagic causes.
After a median follow-up of 39 months, patients in the anagrelide group were significantly more likely than those in the hydroxyurea group to have reached the primary end point (odds ratio, 1.57; 95 percent confidence interval, 1.04 to 2.37; P=0.03). As compared with hydroxyurea plus aspirin, anagrelide plus aspirin was associated with increased rates of arterial thrombosis (P=0.004), serious hemorrhage (P=0.008), and transformation to myelofibrosis (P=0.01) but with a decreased rate of venous thromboembolism (P=0.006). Patients receiving anagrelide were more likely to withdraw from their assigned treatment (P<0.001). Equivalent long-term control of the platelet count was achieved in both groups.
Hydroxyurea plus low-dose aspirin is superior to anagrelide plus low-dose aspirin for patients with essential thrombocythemia at high risk for vascular events.
To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated ...for CNV with ranibizumab or bevacizumab.
Cohort study of patients enrolled in a multicenter, randomized clinical trial.
Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).
Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye.
Development of CNV in the fellow eye.
Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval CI, -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35).
Through 2 years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on 4 SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients.
Proprietary or commercial disclosure may be found after the references.
Autonomous tractor technology is increasingly viewed as a key factor in changing the paradigm of conventional agriculture, allowing a shift away from ever-increasing crop machinery sizes to swarms of ...smaller agricultural robots (agbots). The predicted benefits of agbots include improved productivity relating to key inputs such as labour, energy, and chemicals, as well as yield improvements from improved crop and fallow management and reduced compaction. To understand the economic potential of agbots in Australian cotton production, this analysis applied discounted cash flow analysis to compare changes in income and costs associated with investment in an agbot spraying system. The results showed that switching to agbot spraying is economically feasible compared to two conventional spray platforms in a representative cotton farming enterprise. Compared to a self-propelled sprayer, agbot spraying returned an average annual NPV of $95,750 (at a 5 per cent real discount rate) and a MIRR of 16 per cent, while compared to a three-point linkage tractor sprayer, agbot spraying returned an average annual NPV of $178,603 and a MIRR of 13 per cent. Differences in the NPV and MIRR rules were due to variations in the cashflow patterns. For both scenarios, the largest benefit component was increased crop income from yield gain, followed by avoided machinery capital costs, and reduced chemical costs. Sensitivity testing revealed that, for the self-propelled sprayer scenario, the yield change and farm size variables were both individually significant to the results as they both had the capacity to reduce the NPV below $0 at their maximum range. In the tractor sprayer scenario, the yield gain was the only significant variable, reducing the NPV to $0. With the increasing commercial availability of agbots and the widely predicted benefits, it is timely to understand the economic potential for agbot adoption in the Australian cotton industry. From the results we infer that agbot sprayer technology can be a viable economic technology for adoption in a cotton farming system if yield gains can be generated. The economic viability will also be influenced by a number of factors that will differ between farming operations, and as with any decision, farmers should closely review agbots in their own operational context before investment.
Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable ...in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs.
Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure.
The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania.
We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.
PDF
