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Computers have the potential to be exploited as one of the most exciting examples of instructional media. Yet designers often fail to realize this potential. This is, in part, due to the limitations of hardware and software and, in part, due to the lack of good theory developed through conclusive research. Good examples of computer-based learning may owe more to the imaginative flair of the courseware designer than they do to the application of explicit design guidelines and good learning theory. This paper will therefore consider a variety of issues that may be blocking theoretical development and draw conclusions for future courses of action. This starts with a statement of the problem, first by considering the macro and micro issues, and then by looking at a recent call for help in ComputerBased Learning Environment (CBLE) design. Next, the contribution of instructional design theories will be presented together with a way forward for investigating the issues. Finally the implications for future progress are presented

A proposed psychological model of driving automation

This paper considers psychological variables pertinent to driver automation. It is anticipated that driving with automated systems is likely to have a major impact on the drivers and a multiplicity of factors needs to be taken into account. A systems analysis of the driver, vehicle and automation served as the basis for eliciting psychological factors. The main variables to be considered were: feed-back, locus of control, mental workload, driver stress, situational awareness and mental representations. It is expected that anticipating the effects on the driver brought about by vehicle automation could lead to improved design strategies. Based on research evidence in the literature, the psychological factors were assembled into a model for further investigation

Emerging challenges of the impacts of pharmaceuticals on aquatic ecosystems: A diatom perspective.

Pharmaceuticals are a ubiquitous group of emerging pollutants of considerable importance due to their biological potency and potential to elicit effects in wildlife and humans. Pharmaceuticals have been quantified in terrestrial, marine, fresh, and transitional waters, as well as the fauna and macro-flora that inhabit them. Pharmaceuticals can enter water ways through different human and veterinary pathways with traditional wastewater treatment, unable to completely remove pharmaceuticals, discharging often unknown quantities to aquatic ecosystems. However, there is a paucity of available information regarding the effects of pharmaceuticals on species at the base of aquatic food webs, especially on phytoplankton, with research typically focussing on fish and aquatic invertebrates. Diatoms are one of the main classes of phytoplankton and are some of the most abundant and important organisms in aquatic systems. As primary producers, diatoms generate ∼40 % of the world's oxygen and are a vital food source for primary consumers. Diatoms can also be used for bioremediation of polluted water bodies but perhaps are best known as bio-indicators for water quality studies. However, this keystone, non-target group is often ignored during ecotoxicological studies to assess the effects of pollutants of concern. Observed effects of pharmaceuticals on diatoms have the potential to be used as an indicator of pharmaceutical-induced impacts on higher trophic level organisms and wider ecosystem effects. The aim of this review is to present a synthesis of research on pharmaceutical exposure to diatoms, considering ecotoxicity, bioremediation and the role of diatoms as bio-indicators. We highlight significant omissions and knowledge gaps which need addressing to realise the potential role of diatoms in future risk assessment approaches and help evaluate the impacts of pharmaceuticals in the aquatic environment at local and global scales

OESDs in an on-road study of semi-automated vehicle to human driver handovers

Design of appropriate interaction and human–machine interfaces for the handover of control between vehicle automation and human driver is critical to the success of automated vehicles. Problems in this interfacing between the vehicle and driver have led, in some cases, to collisions and fatalities. In this project, Operator Event Sequence Diagrams (OESDs) were used to design the handover activities to and from vehicle automation. Previous work undertaken in driving simulators has shown that the OESDs can be used to anticipate the likely activities of drivers during the handover of vehicle control. Three such studies showed that there was a strong correlation between the activities drivers represented in OESDs and those observed from videos of drivers in the handover process, in driving simulators. For the current study, OESDs were constructed during the design of the interaction and interfaces for the handover of control to and from vehicle automation. Videos of drivers during the handover were taken on motorways in the UK and compared with the predictions from the OESDs. As before, there were strong correlations between those activities anticipated in the OESDs and those observed during the handover of vehicle control from automation to the human driver. This means that OESDs can be used with some confidence as part of the vehicle automation design process, although validity generalisation remains an important goal for future research

Gestational diabetes mellitus and retinal microvasculature.

BACKGROUND: Small-vessel dysfunction may be an important consequence of chronic hyperglycemia. We examined the association between gestational diabetes mellitus (GDM), a state of transient hyperglycemia during pregnancy, and retinal microvascular changes in pregnant women at 26-28 weeks of pregnancy. METHODS: A total of 1136 pregnant women with singleton pregnancies were recruited during their first trimester at two major Singapore maternity hospitals in an on-going birth cohort study. Participants underwent an oral glucose tolerance test and retinal imaging at 26-28 weeks gestation (n = 542). We used the 1999 World Health Organization (WHO) criteria to define GDM: ≥7.0 mmol/L for fasting glucose and/or ≥7.8 mmol/L for 2-h post-glucose. Retinal microvasculature was measured using computer software (Singapore I Vessel Analyzer, SIVA version 3.0, Singapore Eye Research Institute, Singapore) from the retinal photographs. RESULTS: In a multiple linear regression model adjusting for age, ethnicity and maternal education, mothers with GDM had narrower arteriolar caliber (-1.6 μm; 95% Confidence Interval [CI]: -3.1 μm, -0.2 μm), reduced arteriolar fractal dimension (-0.01 Df; 95% CI: -0.02 Df, -0.001 Df;), and larger arteriolar branching angle (1.8°; 95% CI: 0.3°, 3.3°) than mothers without GDM. After further adjusting for traditional risks of GDM, arteriolar branching angle remained significantly larger in mothers with GDM than those without GDM (2.0°; 95% CI: 0.5°, 3.6°). CONCLUSIONS: GDM was associated with a series of retinal arteriolar abnormalities, including narrower caliber, reduced fractal dimension and larger branching angle, suggesting that transient hyperglycemia during pregnancy may cause small-vessel dysfunction

Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Parental Monitoring During Early Adolescence Deters Adolescent Sexual Initiation: Discrete-Time Survival Mixture Analysis

We used discrete-time survival mixture modeling to examine 5,305 adolescents from the 1997 National Longitudinal Survey of Youth regarding the impact of parental monitoring during early adolescence (ages 14–16) on initiation of sexual intercourse and problem behavior engagement (ages 14–23). Four distinctive parental-monitoring groups were identified and labeled as “High,” “Increasing,” “Decreasing,” and “Low”. About 68% of adolescents received a high level of parental monitoring from ages 14 to 16 (High), 6 and 9% respectively exhibited an accelerated (Increasing) and a decelerated trajectory (Decreasing), and 17% had consistently low parental monitoring (Low). Relative to participants in the Low group, adolescents in the High group delayed sexual initiation by 1.5 years. Males, relative to females, were more likely to have had a low trajectory of parental monitoring, and were more likely to initiate sexual intercourse before age 14. In contrast to White Adolescents, Hispanics and Blacks were less likely to receive High parental monitoring, and had a higher rate of early sexual initiation before age 14. The study demonstrates the temporal relationship of parental monitoring with adolescent sexual initiation from a longitudinal perspective. An increase of parental monitoring across ages is accompanied with a decrease of sexual risk. The continual high level of parental monitoring from ages 14 to 16 also mitigated the risk of engagement in substance use and delinquent behaviors from ages 14 to 23

Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans

Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen