The Dilemma of Direct Democracy

The dilemma of direct democracy is that voters may not always be able to make welfare- improving decisions. Lupia’s seminal work has led us to believe that voters can substitute voting cues for substantive policy knowledge. Lupia, however, emphasized that cues were valuable under certain conditions and not others. In what follows, we present three main findings regarding voters and what they know about California’s Proposition 7. First, much like Lupia reported, we show voters who are able to recall endorsements for or against a ballot measure vote similarly to people who recall certain basic facts about the initiative. We show, second, that voters whose stated policy preferences would otherwise suggest they would favor the “no” position cast their ballots with far less error than do people who favor the “yes” position. One thing this suggests is that many voters may employ a “defensive no” strategy when faced with complex policy choices on the ballot. Our third result is a bit surprising: we find that better- informed voters, whether this information is derived from factual knowledge of the initiative or from knowledge of well-publicized voting cues, are no more likely to make reasoned decisions than those who are, by our measure, uninformed. This suggests that existing theories of voter choice, especially in direct democracy, may be inadequate. We conclude with some preliminary policy recommendations that could help improve the information environment for initiatives and referenda by providing key information on the ballot

Mobile Learning

During the Fall of 2003, the East Carolina University Center for Wireless and Mobile Computing and Sprint PCS/Airgate Communications implemented a project to evaluate the potential of 3G smart phone/handheld computers (3GCD’s) for mobile learning. The first environment that was selected for testing this technology involved on-campus freshman Teaching Fellows in the College of Education. In the spring of 2004, the project was expanded to evaluate the use of the devices with twenty-four students taking an online class in Business, Career, and Technical Education. This article will share information on of the use of 3GCD’s with online students.During the Fall of 2003, the East Carolina University Center for Wireless and Mobile Computing and Sprint PCS/Airgate Communications implemented a project to evaluate the potential of 3G smart phone/handheld computers (3GCD’s) for mobile learning. The first environment that was selected for testing this technology involved on-campus freshman Teaching Fellows in the College of Education. In the spring of 2004, the project was expanded to evaluate the use of the devices with twenty-four students taking an online class in Business, Career, and Technical Education. This article will share information on of the use of 3GCD’s with online students

A Clinical Study on Glucosamine Sulfate versus Combination of Glucosamine Sulfate and NSAIDs in Mild to Moderate Knee Osteoarthritis

Background. Glucosamine may be effective in treating and possibly slowing the progression of Osteoarthritis (OA). It is believed Glucosamine supplements may help to stop cartilage breakdown, build cartilage and decrease swelling. Objective. The objective of this study was glucosamine sulfate versus combination of glucosamine sulfate and Non-Steroidal anti-inflammatory drugs (NSAID) in mild to moderate knee osteoarthritis. Methods. Subjects were randomly recruited from Rheumatology outpatient department after a diagnosis of mild or moderate Osteoarthritis. Study tools like patient data collection form, Western Ontario McMaster Universities Arthritis index (WOMAC) of Osteoarthritis questionnaires and Visual Analog Scale (VAS) were used. Results. After 12 weeks, WOMAC total score the result showed that the significant mean difference between the group A and Group B treatment (P < 0.01), with a combination of GS and NSAIDs reducing VAS pain scores. Thus, it is found that Group B treatments over 4 and 12 weeks produced improved WOMAC and VAS grades. Conclusions. Study results may suggest that the Glucosamine Sulfate has a carryover effect like Disease modifying agents. Long-term treatment of Glucosamine Sulfate may reduce the dependence of NSAIDs usage and delay the disease progression. Thereby we can reduce the NSAIDs side effects and improve the patient's quality of life

Changing trends in residents-as-teachers across graduate medical education

BACKGROUND: Teaching residents how to teach is a critical part of residents' training in graduate medical education (GME). The purpose of this study was to assess the change in resident-as-teacher (RaT) instruction in GME over the past 15 years in the US. METHODS: We used a quantitative and qualitative survey of all program directors (PDs) across specialties. We compared our findings with a previous work from 2000-2001 that studied the same matter. Finally, we qualitatively analyzed PDs' responses regarding the reasons for implementing and not implementing RaT instruction. RESULTS: Two hundred and twenty-one PDs completed the survey, which yields a response rate of 12.6%. Over 80% of PDs implement RaT, an increase of 26.34% compared to 2000-2001. RaT instruction uses multiple methods with didactic lectures reported as the most common, followed by role playing in simulated environments, then observing and giving feedback. Residents giving feedback, clinical supervision, and bedside teaching were the top three targeted skills. Through our qualitative analysis we identified five main reasons for implementing RaT: teaching is part of the residents' role; learners desire formal RaT training; regulatory bodies require RaT training; RaT improves residents' education; and RaT prepares residents for their current and future roles. CONCLUSION: The use of RaT instruction has increased significantly in GME. More and more PDs are realizing its importance in the residents' formative training experience. Future studies should examine the effectiveness of each method for RaT instruction

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Salicylic acid treatment and expression of an RNA-dependent RNA polymerase 1 transgene inhibit lethal symptoms and meristem invasion during tobacco mosaic virus infection in Nicotiana benthamiana.

BACKGROUND: Host RNA-dependent RNA polymerases (RDRs) 1 and 6 contribute to antiviral RNA silencing in plants. RDR6 is constitutively expressed and was previously shown to limit invasion of Nicotiana benthamiana meristem tissue by potato virus X and thereby inhibit disease development. RDR1 is inducible by salicylic acid (SA) and several other phytohormones. But although it contributes to basal resistance to tobacco mosaic virus (TMV) it is dispensable for SA-induced resistance in inoculated leaves. The laboratory accession of N. benthamiana is a natural rdr1 mutant and highly susceptible to TMV. However, TMV-induced symptoms are ameliorated in transgenic plants expressing Medicago truncatula RDR1. RESULTS: In MtRDR1-transgenic N. benthamiana plants the spread of TMV expressing the green fluorescent protein (TMV.GFP) into upper, non-inoculated, leaves was not inhibited. However, in these plants exclusion of TMV.GFP from the apical meristem and adjacent stem tissue was greater than in control plants and this exclusion effect was enhanced by SA. TMV normally kills N. benthamiana plants but although MtRDR1-transgenic plants initially displayed virus-induced necrosis they subsequently recovered. Recovery from disease was markedly enhanced by SA treatment in MtRDR1-transgenic plants whereas in control plants SA delayed but did not prevent systemic necrosis and death. Following SA treatment of MtRDR1-transgenic plants, extractable RDR enzyme activity was increased and Western blot analysis of RDR extracts revealed a band cross-reacting with an antibody raised against MtRDR1. Expression of MtRDR1 in the transgenic N. benthamiana plants was driven by a constitutive 35S promoter derived from cauliflower mosaic virus, confirmed to be non-responsive to SA. This suggests that the effects of SA on MtRDR1 are exerted at a post-transcriptional level. CONCLUSIONS: MtRDR1 inhibits severe symptom development by limiting spread of virus into the growing tips of infected plants. Thus, RDR1 may act in a similar fashion to RDR6. MtRDR1 and SA acted additively to further promote recovery from disease symptoms in MtRDR1-transgenic plants. Thus it is possible that SA promotes MtRDR1 activity and/or stability through post-transcriptional effects.We thank Zhixiang Chen for his advice on the RDR assay protocol. Xiaoqiang Wang and Zhentian Lei at the Samuel Roberts Noble Foundation for the AKTA purification protocol and analysis of recombinant MBP:MtRDR1 fusion protein, respectively. David Baulcombe, Peter Palukaitis, Joel Milner and Lydia Hunter are thanked for stimulating discussions and useful advice and Adrienne Pate for expert technical assistance. FSF was funded by grants from the Cambridge Overseas Trust and the Ministry of Education of Taiwan, and WSL was funded by a studentship from the Biotechnology and Biological Sciences Research Council (BBSRC) and work in the Carr lab was funded by BBSRC grants (BB/D008204/1, BB/D014376/1, BB/J011762/1), The Leverhulme Trust (F/09 741/F, RPG-2012-667), and Cambridge University Isaac Newton Trust. RSN and SRC were funded by the Samuel Roberts Noble Foundation, Inc

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>The inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors.</p> <p>Methods</p> <p>Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by <it>in situ </it>hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM).</p> <p>Results</p> <p>In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms.</p> <p>Conclusions</p> <p>We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.</p

Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care

Background: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the frst 12 months of care. Methods: Demographic and clinical information of 2901 young people who accessed mental health care at age 12–25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to defne three fxed groups for analyses (stage 1a: ‘non-specifc anxious or depressive symptoms’, 1b: ‘attenuated mood or psychotic syndromes’, 2+: ‘full-threshold mood or psychotic syndromes’). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. Results: Of the entire cohort, 2093 young people aged 12–25 years were followed up at least once over the frst 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60–4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36–3.28), develop suicidal ideations (OR=1.92; CI 1.30–2.84) and circadian disturbances (OR=1.94, CI 1.31–2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. Conclusions: The diferential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model’s assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specifc intervention packages

Subtropical mode water variability in a climatologically forced model in the northwestern Pacific Ocean

Author Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 42 (2012): 126–140, doi:10.1175/2011JPO4513.1.A climatologically forced high-resolution model is used to examine variability of subtropical mode water (STMW) in the northwestern Pacific Ocean. Despite the use of annually repeating atmospheric forcing, significant interannual to decadal variability is evident in the volume, temperature, and age of STMW formed in the region. This long time-scale variability is intrinsic to the ocean. The formation and characteristics of STMW are comparable to those observed in nature. STMW is found to be cooler, denser, and shallower in the east than in the west, but time variations in these properties are generally correlated across the full water mass. Formation is found to occur south of the Kuroshio Extension, and after formation STMW is advected westward, as shown by the transport streamfunction. The ideal age and chlorofluorocarbon tracers are used to analyze the life cycle of STMW. Over the full model run, the average age of STMW is found to be 4.1 yr, but there is strong geographical variation in this, from an average age of 3.0 yr in the east to 4.9 yr in the west. This is further evidence that STMW is formed in the east and travels to the west. This is qualitatively confirmed through simulated dye experiments known as transit-time distributions. Changes in STMW formation are correlated with a large meander in the path of the Kuroshio south of Japan. In the model, the large meander inhibits STMW formation just south of Japan, but the export of water with low potential vorticity leads to formation of STMW in the east and an overall increase in volume. This is correlated with an increase in the outcrop area of STMW. Mixed layer depth, on the other hand, is found to be uncorrelated with the volume of STMW.E.M.D. acknowledges support of the Doherty Foundation and National Science Foundation (OCE-0849808). S.R.J was sponsored by the National Science Foundation (OCE-0849808). Participation of S.P. and F.B. was supported by the National Science Foundation by its sponsorship of the National Center for Atmospheric Research.2012-07-0