Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings

The high acute toxicity of acrylonitrile may be a result of its intrinsic biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine has been recommended for treatment of accidental intoxications in acrylonitrile workers, but such recommendations vary internationally. Acrylonitrile is metabolized in humans and experimental animals via two competing pathways; the glutathione-dependent pathway is considered to represent an avenue of detoxication whilst the oxidative pathway leads to a genotoxic epoxide, cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile overexposure or intoxication have occurred within persons having industrial contact with acrylonitrile; the route of exposure was by inhalation and/or by skin contact. The combined observations lead to the conclusion of a much higher impact of the oxidative metabolism of acrylonitrile in humans than in rodents. This is confirmed by differences in the clinical picture of acute life-threatening intoxications in both species, as well as by differential efficacies of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an appropriate measure for antidote therapy of acute acrylonitrile intoxications. Clinical observations also highlight the practical importance of human individual susceptibility differences. Furthermore, differential adduct monitoring, assessing protein adducts with different rates of decay, enables the development of more elaborated biological monitoring strategies for the surveillance of workers with potential acrylonitrile contact.

Healthcare channel consumer insights : supermarkets, pharmacy & general practitioners

Why are consumers different: Heterogeneity in the way consumers categorise products and services – Snack Food Influenced by the individual needs, personal traits, values and goals – Blood Donation Consumers base their choices on information from external sources and prior experiences stored in memory. Intrinsic – prior experience Extrinsic – advertising, blogs, etc

Chinese TEFL teachers’ perceptions about research and influences on their research endeavours

English has always occupied a key position in China’s education. The quality of English education depends largely on the quality of the English teaching force. Improving the overall quality of Teaching English as a Foreign Language (TEFL) teachers entails advancing both their teaching and research competence. This study, with its focus on Chinese TEFL teachers working in a higher education institution, was set up in a context where Chinese higher education colleges are being transformed into universities and research is becoming a crucial aspect of all teachers’ work. This small-scale case study investigated a group of Chinese TEFL teachers’ perceptions about research and their individual and workplace characteristics that influenced their research endeavours. The findings revealed that Chinese TEFL teachers recognised the significance of research for teaching, professional growth and career advancement. However, lack of individual characteristics such as research and disciplinary knowledge, confidence in research and intrinsic motivation impeded their research efforts. Their institution and departments seemed to encourage research; yet, more specific financial and academic support to start and sustain their research endeavours is required. This study’s findings provide implications for both individual teachers and their institutions to engage TEFL teachers more actively in research.

Assessing agronomic and environmental implications of different N fertilisation strategies in subtropical grain cropping systems on Oxisols

A multi-season 15N tracer recovery experiment was conducted on an Oxisol cropped with wheat, maize and sorghum to compare crop N recoveries of different fertilisation strategies and determine the main pathways of N losses that limit N recovery in these agroecosystems. In the wheat and maize seasons, 15N-labelled fertiliser was applied as conventional urea (CONV) and urea coated with a nitrification inhibitor (DMPP). In sorghum, the fate of 15N-labelled urea was monitored in this crop following a legume ley pasture (L70) or a grass ley pasture (G100). The fertiliser N applied to sorghum in the legume-cereal rotation was reduced (70 kg N ha−1) compared to the grass-cereal (100 kg N ha−1) to assess the availability of the N residual from the legume ley pasture. Average crop N recoveries were 73 % (CONV) and 77 % (DMPP) in wheat and 50 % (CONV) and 51 % (DMPP) in maize, while in sorghum were 71 % (L70) and 53 % (G100). Data gathered in this study indicate that the intrinsic physical and chemical conditions of Oxisols can be extremely effective in limiting N losses via deep leaching or denitrification. Elevated crop 15N recoveries can be therefore obtained in subtropical Oxisols using conventional urea while in these agroecosystems DMPP urea has no significant scope to increase fertiliser N recovery in the crop. Overall, introducing a legume phase to limit the fertiliser N requirements of the following cereal crop proved to be the most effective strategy to reduce N losses and increase fertiliser N recovery.

What Costs Accountability? Financial Accountability, Mission and Fundraising in Nonprofits

Although greater calls for accountability have been articulated by academics, policy makers and donors in the recent years, a stream of thought has been questioning where the giving of an account should stop. In conveying the limits to the giving of an account (Messner, 2009) and associated transparency (Roberts, 2009), critical accounting scholars have also pointed to as yet unresolved contradictions intrinsic to accountability (McKernan, 2012), especially when it comes to be operationalised (Joannides, 2012). The impact of accountability's discharging on nonprofits' strategy or operations has to date been underexplored (Dhanni & Connelly, 2012; Tucker & Parker, 2013). Accordingly, this chapter seeks to contribute to this body of literature on the consequences of accountability on fundraising strategies in nonprofits, questioning whether accountability practice may hamper the effectiveness of the nonprofit sector by restraining the fundraising profession. Our chapter seeks to fill a dual theoretical gap. Firstly, only a number of publications have investigated the interplay between accountability and the making of organisational strategy (Parker, 2002, 2003b, 2011, 2012, 2013; Tucker & Parker, 2013). Therefore, we seek to fill a theoretical gap as to the impact of accountability on the conduct of straegic operations. By questioning whether accountability hampers fundraising strategy in non-profits we are also contributing to the literature balancing accountability and the mission. In this literature, it appears that money and the mission are often conflictual, financial managers being often seen by mission advocates as guardians shielding organisational resources (Chiapello, 1993, 1998; Lightbody, 2000, 2003). Another approach shows that making nonprofits accountable to capital and multiple stakeholders (donors, public authorities) leaders to changes in organisational culture (O'Dwyer & Unerman, 2007; Unerman & Bennett, 2004; Underman & O'Dwyer, 2006a, 2006b, 2008). By examining a small number of cases we show how accountability practices result in fundraising adapting and adjusting under such external pressures and constraints. We also show accountability systems may have a direct impact on the conduct of strategic operations, which might hamper mission conduct.

Kids, counselors and troubles-telling : morality-in-action in talk on an Australian children’s helpline

This article begins with the premise that morality is an intrinsic, although often invisible, aspect of everyday social action. Drawn from a corpus of fifty audiorecorded telephone calls to Kids Helpline, an Australian helpline for children and young people, we examine one call to show how the young caller and counsellor co-construct ‘morality-in-action’. Ethnomethodological understandings and, in particular, Sacks’ (1992) description of ‘Class 2’ rules and infractions show how an adolescent caller and counsellor collaboratively assemble moral versions of the caller. In puzzling out possible motives, the caller and counsellor can be seen to be attending to the implications of different moral versions of the caller. This attribution of motives is moral work in action, with motives contingently assembled, displayed and evaluated, with such work understood as displays of moral reasoning. The counselling call makes visible the counsellor’s interactional work to support and empower the client. Analysis such as this offers counsellors ways of understanding and making visible their interactional and moral work within helpline call interactions.

Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data

Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.

Temporal characteristics of melanopsin inputs to the human pupil light reflex

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

What is Statutory Interpretation? A Primer QUT law students

In this Primer, our aims are to explain what statutory interpretation is and why it is important. We also aim to note some of the more difficult concepts and ideas you will need to understand when reading a statute, when deciding if it is relevant to a legal problem, and, if so, how it applies to that problem. We do not aim to provide an overview of the rules of Statutory Interpretation, but only to focus on areas that have created well-known difficulties for students and practitioners alike, such as the concept of the intentions of Parliament and the correct use of intrinsic materials.

An investigation into students' motivation to learn English in higher education in Vietnam

This mixed-methods research explored students' motivation to learn English in an attempt to enhance the quality of teaching and learning English in Vietnamese higher education. An intricate picture of students' motivation was revealed: motivation to learn English to gain pragmatic benefits, to satisfy internal aspirations, and in response to external pressures. Students expressed that feeling connected with significant people (lecturers, peers and parents) enhanced their motivation to learn English. This research has significance at both practical and theoretical levels as it provides important insights into the teaching and learning English in Vietnamese higher education and the literature of second language learning motivation.

Mechanisms of cisplatin resistance: DNA repair and cellular implications

Cisplatin (cis-diamminedichloroplatinum (II)), is a platinum based chemotherapeutic employed in the clinic to treat patients with lung, ovarian, colorectal or head and neck cancers. Cisplatin acts to induce tumor cell death via multiple mechanisms. The best characterized mode of action is through irreversible DNA cross-links which activate DNA damage signals leading to cell death via the intrinsic mitochondrial apoptosis pathway. However, the primary issue with cisplatin is that while patients initially respond favorably, sustained cisplatin therapy often yields chemoresistance resulting in therapeutic failure. In this chapter, we review the DNA damage and repair pathways that contribute to cisplatin resistance. We also examine the cellular implications of cisplatin resistance that may lead to selection of subpopulations of cells within a tumor. In better understanding the mechanisms conferring cisplatin resistance, novel targets may be identified to restore drug sensitivity.

A determinism and desire: Some neurological processes in perceiving the design object

The environment moderates behaviour using a subtle language of ‘affordances’ and ‘behaviour-settings’. Affordances are environmental offerings. They are objects that demand action; a cliff demands a leap and binoculars demand a peek. Behaviour-settings are ‘places;’ spaces encoded with expectations and meanings. Behaviour-settings work the opposite way to affordances; they demand inhibition; an introspective demeanour in a church or when under surveillance. Most affordances and behaviour-settings are designed, and as such, designers are effectively predicting brain reactions. • Affordances are nested within, and moderated by behaviour-settings. Both trigger automatic neural responses (excitation and inhibition). These, for the best part cancel each other out. This balancing enables object recognition and allows choice about what action should be taken (if any). But when excitation exceeds inhibition, instinctive action will automatically commence. In positive circumstances this may mean laughter or a smile. In negative circumstances, fleeing, screaming or other panic responses are likely. People with poor frontal function, due to immaturity (childhood or developmental disorders) or due to hypofrontality (schizophrenia, brain damage or dementia) have a reduced capacity to balance excitatory and inhibitory impulses. For these people, environmental behavioural demands increase with the decline of frontal brain function. • The world around us is not only encoded with symbols and sensory information. Opportunities and restrictions work on a much more primal level. Person/space interactions constantly take place at a molecular scale. Every space we enter has its own special dynamic, where individualism vies for supremacy between the opposing forces of affordance-related excitation and the inhibition intrinsic to behaviour-settings. And in this context, even a small change–the installation of a CCTV camera can turn a circus to a prison. • This paper draws on cutting-edge neurological theory to understand the psychological determinates of the everyday experience of the designed environment.

Some major problems with existing models and terminology associated with kimberlite pipes from a volcanological perspective, and some suggestions

Five significant problems hinder advances in understanding of the volcanology of kimberlites: (1) kimberlite geology is very model driven; (2) a highly genetic terminology drives deposit or facies interpretation; (3) the effects of alteration on preserved depositional textures have been grossly underestimated; (4) the level of understanding of the physical process significance of preserved textures is limited; and, (5) some inferred processes and deposits are not based on actual, modern volcanological processes. These issues need to be addressed in order to advance understanding of kimberlite volcanological pipe forming processes and deposits. The traditional, steep-sided southern African pipe model (Class I) consists of a steep tapering pipe with a deep root zone, a middle diatreme zone and an upper crater zone (if preserved). Each zone is thought to be dominated by distinctive facies, respectively: hypabyssal kimberlite (HK, descriptively called here massive coherent porphyritic kimberlite), tuffisitic kimberlite breccia (TKB, descriptively here called massive, poorly sorted lapilli tuff) and crater zone facies, which include variably bedded pyroclastic kimberlite and resedimented and reworked volcaniclastic kimberlite (RVK). Porphyritic coherent kimberlite may, however, also be emplaced at different levels in the pipe, as later stage intrusions, as well as dykes in the surrounding country rock. The relationship between HK and TKB is not always clear. Sub-terranean fluidisation as an emplacement process is a largely unsubstantiated hypothesis; modern in-vent volcanological processes should initially be considered to explain observed deposits. Crater zone volcaniclastic deposits can occur within the diatreme zone of some pipes, indicating that the pipe was largely empty at the end of the eruption, and subsequently began to fill-in largely through resedimentation and sourcing of pyroclastic deposits from nearby vents. Classes II and III Canadian kimberlite models have a more factual, descriptive basis, but are still inadequately documented given the recency of their discovery. The diversity amongst kimberlite bodies suggests that a three-model classification is an over-simplification. Every kimberlite is altered to varying degrees, which is an intrinsic consequence of the ultrabasic composition of kimberlite and the in-vent context; few preserve original textures. The effects of syn- to post-emplacement alteration on original textures have not been adequately considered to date, and should be back-stripped to identify original textural elements and configurations. Applying sedimentological textural configurations as a guide to emplacement processes would be useful. The traditional terminology has many connotations about spatial position in pipe and of process. Perhaps the traditional terminology can be retained in the industrial situation as a general lithofacies-mining terminological scheme because it is so entrenched. However, for research purposes a more descriptive lithofacies terminology should be adopted to facilitate detailed understanding of deposit characteristics, important variations in these, and the process origins. For example every deposit of TKB is different in componentry, texture, or depositional structure. However, because so many deposits in many different pipes are called TKB, there is an implication that they are all similar and that similar processes were involved, which is far from clear.

Direct mapping of hippocampal surfaces with intrinsic shape context

We propose in this paper a new method for the mapping of hippocampal (HC) surfaces to establish correspondences between points on HC surfaces and enable localized HC shape analysis. A novel geometric feature, the intrinsic shape context, is defined to capture the global characteristics of the HC shapes. Based on this intrinsic feature, an automatic algorithm is developed to detect a set of landmark curves that are stable across population. The direct map between a source and target HC surface is then solved as the minimizer of a harmonic energy function defined on the source surface with landmark constraints. For numerical solutions, we compute the map with the approach of solving partial differential equations on implicit surfaces. The direct mapping method has the following properties: (1) it has the advantage of being automatic; (2) it is invariant to the pose of HC shapes. In our experiments, we apply the direct mapping method to study temporal changes of HC asymmetry in Alzheimer's disease (AD) using HC surfaces from 12 AD patients and 14 normal controls. Our results show that the AD group has a different trend in temporal changes of HC asymmetry than the group of normal controls. We also demonstrate the flexibility of the direct mapping method by applying it to construct spherical maps of HC surfaces. Spherical harmonics (SPHARM) analysis is then applied and it confirms our results on temporal changes of HC asymmetry in AD.