Standard setting anchor statements: a double cross-over trial of two different methods.

This article was migrated. The article was marked as recommended. Context: We challenge the philosophical acceptability of the Angoff method, and propose an alternative method of standard setting based on how important it is for candidates to know the material each test item assesses, and not how difficult it is for a subgroup of candidates to answer each item. Methods: The practicalities of an alternative method of standard setting are evaluated here, for the first time, with direct comparison to an Angoff method. To negate bias due to any leading effects, a prospective cross-over design was adopted involving two groups of judges (n=7 and n=8), both of which set the standards for the same two 100 item multiple choice question tests, by the two different methods. Results: Overall, we found that the two methods took a similar amount of time to complete. The alternative method produced a higher cut-score (by 12-14%), and had a higher degree of variability between judges' cut-scores (by 5%). When using the alternative method, judges reported a small, but statistically significant, increase in their confidence to decide accurately the standard (by 3%). Conclusion: This is a new approach to standard setting where the quantitative differences are slight, but there are clear qualitative advantages associated with use of the alternative method.

Host Range Expansion of an Endemic Insect Herbivore is Associated With High Nitrogen and Low Fibre Content in Exotic Pasture Plants.

Endemic moth species of the genus Wiseana spp. (Hepialidae) have become serious pests of introduced pasture plants in New Zealand. The original native host plants of these moths have not been confirmed. This study investigated the performance (survival, development time, weight gain) of three Wiseana species on seven putative host plants: five native and two exotic species. The aim was to identify native hosts for the three Wiseana species and to compare their performance on native plants and exotic pasture plants. The chemical composition of the seven putative host plants was investigated to compare native and exotic plant chemistries, and to test for associations between plant characteristics and performance of selected Wiseana species. Carbon, nitrogen, silica and fibre contents were measured for each plant species; primary metabolite composition was determined by gas chromatography-mass spectrometry. For the three moth species, increased survival and weight gain were significantly associated with high nitrogen and low fibre contents in one exotic host plant, white clover (Trifolium repens), although one species, W. umbraculata, did not complete development to adult on any of the plants tested, including clover. Two exotic plants (T. repens, Lolium perenne × Lolium multiflorum), and two native plants (Aciphylla squarrosa and Festuca actae) supported W. copularis development to the adult stage, but only one exotic (T. repens) and one native (F. actae) species supported complete development of W. cervinata. Exotic and native plant species had distinct metabolite profiles, but there was no significant association between metabolite composition and Wiseana performance. We conclude that W. copularis and W. cervinata, but not W. umbraculata, have expanded their host range, because of their ability to use both native and new hosts. No evidence was found for a host shift, i.e., a loss of performance on the ancestral host compared with the new host.

Development of a Yersinia entomophaga bait for control of larvae of the porina moth (Wiseana spp.), a pest of New Zealand improved grassland systems.

BACKGROUND: Porina is the common name for moths and larvae of the genus Wiseana (Lepidoptera: Hepialidae), some of which are significant pasture pests in New Zealand. Because of environmental concerns and the non-target effects of insecticide control measures, biological alternatives for the control of insect pests such as porina are required. RESULTS: Using a food preference assay and time-lapse photography, a range of low-cost food ingredients were assessed for their palatability to porina larvae. Lead candidates were combined into extruded bait variants, allowing assessment of their palatability to porina larvae. A composite bait consisting of palatable ingredients was developed, into which the porina-active entomopathogen Yersinia entomophaga was incorporated. A 7 day minimum median lethal dose of approximately 6.0 × ±1 × 106 Y. entomophaga cells per 0.02 g of bait was defined. Field trials showed that the mean change in larval density over time differed between treatments, with Y. entomophaga bait applied at 87 kg ha-1 resulting in a mean 65% reduction in larval density relative to the control plots, and diflubenzuron treatment resulting in a mean 77% reduction relative to the control plots. The mean dry matter yields over the course of the trial were highest for diflubenzuron (5029 kg ha-1 ), followed by the Y. entomophaga (4783 kg ha-1 ) and control (4673 kg ha-1 ) treatments. CONCLUSIONS: The bacterium Y. entomophaga applied as a composite bait offers an environmentally sustainable approach for porina pest control. © 2019 Society of Chemical Industry.

Impact of Progress testing on the learning experiences of students in medicine, dentistry and dental therapy.

AIMS: To investigate the impact of progress testing on the learning experiences of undergraduate students in three programs namely, medicine, dentistry and dental therapy. METHODS: Participants were invited to respond to an online questionnaire to share their perceptions and experiences of progress testing. Responses were recorded anonymously, but data on their program, year of study, age, gender, and ethnicity were also captured on a voluntary basis. RESULTS: A total of 167 participants completed the questionnaire yielding a response rate of 27.2% (n = 167). These included 96 BMBS students (27.4%), 56 BDS students (24.7%), and 15 BScDTH students (39.5%). A 3 -Program (BMBS, BDS, BScDTH) by 8-Topic (A-H) mixed analysis of variance (ANOVA) was conducted on the questionnaire responses. This revealed statistically significant main effects of Program and Topic, as well as a statistically significant interaction between the two (i.e. the pattern of topic differences was different across programs). CONCLUSIONS: Undergraduate students in medicine, dentistry, and dental therapy and hygiene regarded PT as a useful assessment to support their learning needs. However, in comparison to students in dentistry and dental therapy and hygiene, the perceptions of medical students were less positive in several aspects of PT.

Genetic variation within species and haplotypes of the Wiseana (Lepidoptera: Hepialidae) complex and development of non-sequenced based identification tools to aid field studies.

BACKGROUND: Porina is the common name used to describe moths and caterpillars of the seven endemic species and three haplotypes of Wiseana in New Zealand. Several species have adapted to eating introduced pasture plants; however, a paucity of defining morphological characteristics has meant that porina are grouped as indistinguishable species within a complex. This study aimed to develop non-sequencing identification methods for porina species. RESULTS: We sequenced 1718 bp of the mitochondrial cytochrome oxidase genes for all Wiseana species and haplotypes using 75 specimens collected from 42 sites throughout New Zealand. Two identification methods were developed; the high-resolution melt method uses 106 bp of the cytochrome oxidase I gene, and the restriction fragment polymorphism method uses a larger 700 bp region from the same gene. Validation was performed on a further 275 specimens. Melt curve profiles varied more with population heterogeneity than digest results. In both methods, W. mimica and W. jocosa were inseparable. W. fuliginea grouped with W. mimica and W. jocosa in the restriction method, but the melt curve profile differed. CONCLUSION: Until now, ecological studies of porina at the species level have been implausible. Our non-sequencing based methods allow rapid identification of moths and caterpillars to species and haplotype level, paving the way for ecological studies of pasture pest species and the development of species-specific mitigation strategies. © 2017 Society of Chemical Industry.

A novel method for non-invasively detecting the severity and location of aortic aneurysms.

The influence of an aortic aneurysm on blood flow waveforms is well established, but how to exploit this link for diagnostic purposes still remains challenging. This work uses a combination of experimental and computational modelling to study how aneurysms of various size affect the waveforms. Experimental studies are carried out on fusiform-type aneurysm models, and a comparison of results with those from a one-dimensional fluid-structure interaction model shows close agreement. Further mathematical analysis of these results allows the definition of several indicators that characterize the impact of an aneurysm on waveforms. These indicators are then further studied in a computational model of a systemic blood flow network. This demonstrates the methods' ability to detect the location and severity of an aortic aneurysm through the analysis of flow waveforms in clinically accessible locations. Therefore, the proposed methodology shows a high potential for non-invasive aneurysm detectors/monitors.

Is the Invasive Species Listronotus bonariensis (Kuschel) (Coleoptera: Curculionidae) (Argentine Stem Weevil) a Threat to New Zealand Natural Grassland Ecosystems?

Listronotus bonariensis (Argentine stem weevil) is a stem-boring weevil that has become a major pasture pest in New Zealand, and cool climate turf grass in Australia. This species is also frequently found in native tussock grassland in New Zealand. Laboratory and field trials were established to determine the risk posed to both seedlings and established plants of three native grass species compared to what happens with a common host of this species, hybrid ryegrass (L. perenne X L. multiflorum). Adult weevil feeding damage scores were higher on Poa colensoi and Festuca novae-zelandiae than Chionochloa rigida. Oviposition was lower on P. colensoi than hybrid ryegrass, and no eggs were laid on F. novae-zelandiae. In field trials using the same four species established as spaced plants L. bonariensis laid more eggs per tiller in ryegrass in a low altitude pasture site than in ryegrass in a higher altitude site. No eggs were found on the three native grass species at the tussock sites, and only low numbers were found on other grasses at the low altitude pasture site. Despite this, numbers of adult weevils were extracted from the plants in the field trials. These may have comprised survivors of the original weevils added to the plants, together with new generation weevils that had emerged during the experiment. Irrespective, higher numbers were recovered from the tussock site plants than from those from the pasture site. It was concluded that L. bonariensis is likely to have little overall impact, but a greater impact on native grass seedling survival than on established plants.

Regulation of protein-ligand binding affinity by hydrogen bond pairing.

Hydrogen (H)-bonds potentiate diverse cellular functions by facilitating molecular interactions. The mechanism and the extent to which H-bonds regulate molecular interactions are a largely unresolved problem in biology because the H-bonding process continuously competes with bulk water. This interference may significantly alter our understanding of molecular function, for example, in the elucidation of the origin of enzymatic catalytic power. We advance this concept by showing that H-bonds regulate molecular interactions via a hitherto unappreciated donor-acceptor pairing mechanism that minimizes competition with water. On the basis of theoretical and experimental correlations between H-bond pairings and their effects on ligand binding affinity, we demonstrate that H-bonds enhance receptor-ligand interactions when both the donor and acceptor have either significantly stronger or significantly weaker H-bonding capabilities than the hydrogen and oxygen atoms in water. By contrast, mixed strong-weak H-bond pairings decrease ligand binding affinity due to interference with bulk water, offering mechanistic insight into why indiscriminate strengthening of receptor-ligand H-bonds correlates poorly with experimental binding affinity. Further support for the H-bond pairing principle is provided by the discovery and optimization of lead compounds targeting dietary melamine and Clostridium difficile toxins, which are not realized by traditional drug design methods. Synergistic H-bond pairings have therefore evolved in the natural design of high-affinity binding and provide a new conceptual framework to evaluate the H-bonding process in biological systems. Our findings may also guide wider applications of competing H-bond pairings in lead compound design and in determining the origin of enzymatic catalytic power.

Alcohol 'pre-loading': a review of the literature.

AIM: To review the international literature concerning pre-loading (PL); this is drinking before going out to pubs and bars. METHOD: A literature review conducted in May 2013 using the EBSCO database entering the following search terms 'pre-loading', 'front-loading', 'pre-partying' and 'pre-drinking'. Thereafter, the reference lists were checked for further relevant articles. The review consisted of 40 articles of which 11 were excluded because PL was not the primary unit of analysis or they did not fulfil a quality assurance criterion. RESULTS: Despite being an internationally widespread development to date, most of the research on this has been from the USA and UK. The majority of US studies have been concerned with PL in a college and high school setting, while the research in the UK has mainly concentrated on the correlation/relationship between PL and what takes place when drinkers enter pubs and bars later in the evening. A consistent finding was that PL is associated with greater alcohol consumption, intoxication and alcohol-related risks. The price of alcohol and achieving intoxication were the main motivations for PL. However, other reasons included a chance to meet members of the opposite sex or own friends in surroundings that encouraged interaction rather than intoxication. CONCLUSION: PL should be regarded as part of a wider drinking culture and understood within the context of what individuals require from a night out or staying in when drinking. There is little evidence to suggest that PL is a risk factor for admissions to accident and emergency services.

Non-invasive imaging of tumors by monitoring autotaxin activity using an enzyme-activated near-infrared fluorogenic substrate.

Autotaxin (ATX), an autocrine motility factor that is highly upregulated in metastatic cancer, is a lysophospholipase D enzyme that produces the lipid second messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Dysregulation of the lysolipid signaling pathway is central to the pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has emerged as an important source of biomarkers and therapeutic targets. Herein we describe development and validation of a fluorogenic analog of LPC (AR-2) that enables visualization of ATX activity in vivo. AR-2 exhibits minimal fluorescence until it is activated by ATX, which substantially increases fluorescence in the near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In mice with orthotopic ATX-expressing breast cancer tumors, ATX activated AR-2 fluorescence. Administration of AR-2 to tumor-bearing mice showed high fluorescence in the tumor and low fluorescence in most healthy tissues with tumor fluorescence correlated with ATX levels. Pretreatment of mice with an ATX inhibitor selectively decreased fluorescence in the tumor. Together these data suggest that fluorescence directly correlates with ATX activity and its tissue expression. The data show that AR-2 is a non-invasive and selective tool that enables visualization and quantitation of ATX-expressing tumors and monitoring ATX activity in vivo.

An interesting case of acute, severe postoperative hyponatraemia following carotid endarterectomy.

A 62-year-old man with no major comorbidities became acutely hyponatraemic on the second postoperative day following a routine carotid endarterectomy. He developed a headache, became hypertensive and confused, and then had a seizure and required intubation and admission to the intensive care unit. A CT angiogram of his head and carotid arteries was normal, as was a subsequent MRI head. His serum and urine osmolality were low. He was treated by fluid restriction and his hyponatraemia resolved over 3 days. On discontinuation of sedation the patient woke up appropriately. The cause of his hyponatraemia was initially a mystery but when questioned by the medical team he admitted that he drank about 5 litres of water in the afternoon on the second postoperative day. At this point the diagnosis of dilutional hypervolaemic hyponatraemia secondary to water intoxication could be made.

Characterization of polymerized liposomes using a combination of dc and cyclical electrical field-flow fractionation.

Characterization of polymerized liposomes (PolyPIPosomes) was carried out using a combination of normal dc electrical field-flow fractionation and cyclical electrical field-flow fractionation (CyElFFF) as an analytical technique. The constant nature of the carrier fluid and channel configuration for this technique eliminates many variables associated with multidimensional analysis. CyElFFF uses an oscillating field to induce separation and is performed in the same channel as standard dc electrical field-flow fractionation separation. Theory and experimental methods to characterize nanoparticles in terms of their sizes and electrophoretic mobilities are discussed in this paper. Polystyrene nanoparticles are used for system calibration and characterization of the separation performance, whereas polymerized liposomes are used to demonstrate the applicability of the system to biomedical samples. This paper is also the first to report separation and a higher effective field when CyElFFF is operated at very low applied voltages. The technique is shown to have the ability to quantify both particle size and electrophoretic mobility distributions for colloidal polystyrene nanoparticles and PolyPIPosomes.

Home drinking in the UK: trends and causes.

AIMS: To explore the trend in the UK to consume alcohol at home rather than at licensed premises. METHODS: A Medline search entering the terms 'home drinking', 'alcohol' and 'adult' covering the period 2000-2011 yielded 48 articles, of which 6 met the criteria to be included in the review. Grey literature including survey and market research data were reviewed. RESULTS: In the UK, since 1970 there has been trend for beer to be consumed at home more often than in licensed premises and that the overall trend towards greater home drinking has increased since 2000. The main reasons given are convenience, cost, safety, autonomy and stress relief. There has also been an increase in the practice known as 'pre-loading' (drinking before going out). Adults who drink mainly at home report that they are aware that they run a risk of higher overall alcohol consumption but tend to play down the possibility that increased consumption may lead to longer-term harm. CONCLUSION: Home drinking trends may have long-term public health consequences. Greater understanding of the drivers of this trend will help policy-makers to respond to these societal changes.

Impelling and inhibitory forces in aggression: sex-of-target and relationship effects.

The finding of symmetry in intimate partner aggression is now generally accepted, but the convergence of male and female rates in these relationships remains unexplained. From qualitative analysis of male and female focus group discussions, we identified factors believed to influence the expression of aggression toward targets differing in sex and degree of intimacy. These factors were then used to construct a questionnaire in which 355 respondents indicated the applicability of the items to conflicts with a partner, a same-sex friend, and an opposite-sex friend. Principal component analysis revealed a clear two-factor structure of impelling forces (tending to provoke or initiate aggression) and inhibitory forces (tending to suppress or diminish the likelihood of aggression). Participants' scores on scales derived from these two factors were used in the subsequent analyses. Men reported lower inhibition and greater impulsion toward same-sex friends than to female friends and partners, who did not differ significantly from one another. Women showed lower inhibition to male targets, regardless of relationship, than to a female target. However, women rated their male partners as significantly higher on impelling forces than their male friends, who in turn were rated significantly higher than female friends. The results are broadly consistent with a sex-of-target effect corresponding to a chivalry norm held by both sexes that inhibits the expression of aggression toward women. The reasons why women are especially impelled to aggression by intimate partners are explored. Disaggregating the dynamics of interpersonal conflict into impelling and inhibitory components may prove useful in understanding and treating dispute escalation and resolution.

A chemical proteomics approach to phosphatidylinositol 3-kinase signaling in macrophages.

Prior work using lipid-based affinity matrices has been done to investigate distinct sets of lipid-binding proteins, and one series of experiments has proven successful in mammalian cells for the proteome-wide identification of lipid-binding proteins. However, most lipid-based proteomics screens require scaled up sample preparation, are often composed of multiple cell types, and are not adapted for simultaneous signal transduction studies. Herein we provide a chemical proteomics strategy that uses cleavable lipid "baits" with broad applicability to diverse biological samples. The novel baits were designed to avoid preparative steps to allow functional proteomics studies when the biological source is a limiting factor. Validation of the chemical baits was first confirmed by the selective isolation of several known endogenous phosphatidylinositol 3-kinase signaling proteins using primary bone marrow-derived macrophages. The use of this technique for cellular proteomics and MS/MS analysis was then demonstrated by the identification of known and potential novel lipid-binding proteins that was confirmed in vitro for several proteins by direct lipid-protein interactions. Further to the identification, the method is also compatible with subsequent signal transduction studies, notably for protein kinase profiling of the isolated lipid-bound protein complexes. Taken together, this integration of minimal scale proteomics, lipid chemistry, and activity-based readouts provides a significant advancement in the ability to identify and study the lipid proteome of single, relevant cell types.

Fluorogenic phospholipid substrate to detect lysophospholipase D/autotaxin activity.

[reaction: see text] Lysophospholipase D (lysoPLD), also known as autotaxin (ATX), is an important source of the potent mitogen lysophosphatidic acid (LPA). Two fluorogenic substrate analogues for lysoPLD were synthesized in nine steps from (S)-PMB-glycerol. The substrates (FS-2 and FS-3) show significant increases in fluorescence when treated with recombinant ATX and have potential applications in screening for this emerging drug target.

Phosphoinositide-containing polymerized liposomes: stable membrane-mimetic vesicles for protein-lipid binding analysis.

Stable phosphoinositide (PIP(n))-containing liposomes were prepared using polydiacetylene photochemistry. Tethered pentacosadiynyl inositol polyphosphate (InsP(n)) analogues of Ins(1,3,4)P(3), Ins(1,4,5)P(3), and Ins(1,3,4,5)P(4) were synthesized, incorporated into vesicles made up of diyne-phosphatidylcholine and -phosphatidylethanolamine, and polymerized by UV irradiation. The polymerized liposome nanoparticles showed markedly increased stability over conventional PIP(n)-containing vesicles as a result of the covalent conjugated ene-yne network in the acyl chains. The polymerized liposomes were specifically recognized by PIP(n) binding PH domains in liposome overlay assays and amplified luminescent proximity homogeneous assays. Moreover, the biotin moiety allowed attachment of the nanoparticles to a streptavidin-coated sensor chips in surface plasmon resonance (SPR) sensor. The PIP(n) headgroups displayed on SPR sensors showed higher affinities for PH domains and PIP(n) monoclonal antibodies than did monomeric PIP(n)-analogues with biotinylated acyl chains.

Modification of protein sub-nuclear localization by synthetic phosphoinositides: evidence for nuclear phosphoinositide signaling mechanisms.

PtdInsPs are critical signaling molecules that regulate diverse cellular functions. One method to study PtdInsP biology involves using synthetic PtdInsP analogs to activate endogenous PtdInsP-mediated events in living cells. Such methodology has been successfully employed to explore the role of several PtdInsP-biological outcomes in the cytoplasm. However, this strategy has not previously been used to examine the function of PtdInsPs in the nucleus of live cells, primarily because there has not been a well-defined PtdInsP-binding protein to provide functional nuclear readouts. Here we have shown that synthetic PtdIns(5)P analogs access and function in the nucleus. We have found that these molecules modify the sub-nuclear localization of PHD finger-containing proteins in live cells and in real time. This work demonstrates that synthetic PtdInsPs and PtdInsP derivatives may be powerful tools for probing nuclear PtdInsP functions. Finally, our work supports a model that endogenous PtdInsPs regulate sub-nuclear localization and function of endogenous nuclear PtdInsP-binding proteins.