Creating an employment ready graduate:stakeholder perspectives of internship programmes and their ability to enhance the graduate employability skills set

Purpose: The aims of this research are to examine stakeholder perspectives of the use and usefulness of graduate attributes which are embedded into the curriculum of a UK university and to evaluate the potential of these graduate attributes to go beyond institutional pedagogy and enhance the employability skills set of graduates.Design/methodology/approach: The research used a mixed method to elicit perspectives of a University’s graduate attributes, interviewing employers and surveying students using a self-assessment tool and convenience sampling approach. Findings: The research found that there are key attributes for the success of University-led graduate attributes which include engagement from stakeholders with those attributes, commitment from teaching staff towards the development of identified attributes, appropriate time to align and embed attributes into the curriculum and with the needs of stakeholders and a framework which compliments institutional research and is properly resourced (Al-Mahood and Gruba, 2007). No one graduate attribute works in isolation, they have to be part of a measured and balanced model or framework to address the multi-faceted nature of graduate employability. The research reveals that work-based initiatives were the most valued by graduates and employers alike, which are arguably easier to teach as it is learning by doing as opposed to developing generic softer skills which are not valued highly by graduates in respect to employment. The findings support existing research that graduates value graduate attributes which involve work based learning activities as a means to gain employability skills and employment. Practical and social implications: The research findings should provide Universities and Colleges from both within and out with the UK with a blueprint from which to create or refresh existing University led graduate attributes. Originality/value: The findings from this paper consolidate existing research in the area of graduate employability and take research forward in the areas of graduate attributes, the measurement of these attributes and their currency in terms of employability and employer synergy

Rapid Adaptation of Visual Search in Simulated Hemianopia

Patients with homonymous hemianopia have altered visual search patterns, but it is unclear how rapidly this develops and whether it reflects a strategic adaptation to altered perception or plastic changes to tissue damage. To study the temporal dynamics of adaptation alone, we used a gaze-contingent display to simulate left or right hemianopia in 10 healthy individuals as they performed 25 visual search trials. Visual search was slower and less accurate in hemianopic than in full-field viewing. With full-field viewing, there were improvements in search speed, fixation density, and number of fixations over the first 9 trials, then stable performance. With hemianopic viewing, there was a rapid shift of fixation into the blind field over the first 5-7 trials, followed by continuing gradual improvements in completion time, number of fixations, and fixation density over all 25 trials. We conclude that in the first minutes after onset of hemianopia, there is a biphasic pattern of adaptation to altered perception: an early rapid qualitative change that shifts visual search into the blind side, followed by more gradual gains in the efficiency of using this new strategy, a pattern that has parallels in other studies of motor learnin

Cost-Effectiveness of Disease-Modifying Therapies in the Management of Multiple Sclerosis for the Medicare Population

AbstractObjectiveTo evaluate the cost-effectiveness of disease-modifying therapies (DMTs) for the management of multiple sclerosis (MS) compared to best supportive care in the United States.MethodsCost-effectiveness analysis was undertaken using a state transition model of disease natural history and the impact of DMTs for the representative Medicare beneficiary with MS. Costs and outcomes were evaluated from the health-care payer perspective using a 50-year time horizon. Natural history data were drawn from a longitudinal cohort study. The effectiveness of the DMTs was evaluated through a systematic review. Utility data were taken from a study of patients with clinically definite MS in Nova Scotia. Resource use and cost data were derived from the Sonya Slifka database and associated literature.ResultsWhen based on placebo-controlled evidence, the marginal cost-effectiveness of interferon beta (IFNβ) and glatiramer acetate compared to best supportive care is expected to be in excess of $100,000 per quality-adjusted life-year gained. When evidence from head-to-head trials is incorporated into the model, the cost-effectiveness of 6 MIU IFNβ-1a is expected to be considerably less favorable. Treatment discontinuation upon progression to Expanded Disability Status Scale 7.0 is expected to improve the cost-effectiveness of all DMTs.ConclusionsFurther research is required to examine the long-term clinical effectiveness and cost-effectiveness of these therapies. There is no definitive guidance in the United States concerning discontinuation of DMTs; this study suggests that the prudent use of a treatment discontinuation rule may considerably improve the cost-effectiveness of DMTs

Rational Design of Selective and Bioactive Inhibitors of the Mycobacterium Tuberculosis Proteasome

The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response. Proteasome inhibitors could render Mtb susceptible to the immune system, but they would only be therapeutically viable if they do not inhibit the essential 20S counterpart in humans. Selective inhibitors of the Mtb 20S were designed and synthesized on the bases of both its unique substrate preferences and the structures of substrate-mimicking covalent inhibitors of eukaryotic proteasomes called syringolins. Unlike the parent syringolins, the designed analogues weakly inhibit the human 20S (Hs 20S) proteasome and preferentially inhibit Mtb 20S over the human counterpart by as much as 74-fold. Moreover, they can penetrate the mycobacterial cell envelope and render Mtb susceptible to nitric oxide-mediated stress. Importantly, they do not inhibit the growth of human cell lines in vitro and thus may be starting points for tuberculosis drug development.National Institutes of Health (U.S.) (Grant AI-16892

Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines

Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs.National Institutes of Health (U.S.) (Grant AI-16892

Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. Ring cycle: The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI-like) and phosphatidylethanolamine-binding proteins (PEBP-like).BBSRCSyngent

Editosome Accessory Factors KREPB9 and KREPB10 in Trypanosoma brucei

Multiprotein complexes, called editosomes, catalyze the uridine insertion and deletion RNA editing that forms translatable mitochondrial mRNAs in kinetoplastid parasites. We have identified here two new U1-like zinc finger proteins that associate with editosomes and have shown that they are related to KREPB6, KREPB7, and KREPB8, and thus we have named them Kinetoplastid RNA Editing Proteins, KREPB9 and KREPB10. They are conserved and syntenic in trypanosomatids although KREPB10 is absent in Trypanosoma vivax and both are absent in Leishmania. Tandem affinity purification (TAP)-tagged KREPB9 and KREPB10 incorporate into ∼20S editosomes and/or subcomplexes thereof and preferentially associate with deletion subcomplexes, as do KREPB6, KREPB7, and KREPB8. KREPB10 also associates with editosomes that are isolated via a chimeric endonuclease, KREN1 in KREPB8 RNA interference (RNAi) cells, or MEAT1. The purified complexes have precleaved editing activities and endonuclease cleavage activity that appears to leave a 5′ OH on the 3′ product. RNAi knockdowns did not affect growth but resulted in relative reductions of both edited and unedited mitochondrial mRNAs. The similarity of KREPB9 and KREPB10 to KREPB6, KREPB7, and KREPB8 suggests they may be accessory factors that affect editing endonuclease activity and as a consequence may affect mitochondrial mRNA stability. KREPB9 and KREPB10, along with KREPB6, KREPB7, and KREPB8, may enable the endonucleases to discriminate among and accurately cleave hundreds of different editing sites and may be involved in the control of differential editing during the life cycle of T. brucei