7,109 research outputs found

    Exploring the Factors Associated with Online Financial and Performance Disclosure in Nonprofits

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    Informed by theories of technological innovation, this paper develops and empirically tests a web disclosure adoption model. In order to test the model, a questionnaire was administered to a sample of 775 organizations in an eight-county regional area in the Northeastern United States. Results reveal that Chief Executive Officer (CEO) and organizational characteristics are related to web disclosure adoption. Specifically, there is more disclosure of performance information online when the CEO believes that the web is useful for promoting transparency and accountability when the organization views the web as a communication or strategic tool, when more employees have technical expertise, and when the board of directors is more supportive of web technology. We found more web disclosure of financial information when the organization possesses the technological readiness for web disclosure. This paper contributes to research by identifying the main factors that facilitate web disclosure adoption in nonprofit contexts

    Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8+ and CD4+ T-cell responses from chronically infected individuals

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    Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-γ) and β-chemokines. Furthermore, canarypox virus-infected DCs were \u3e30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-γ-secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+ and CD4+ helper responses in vivo

    Vibrational Satellites of C2_2S, C3_3S, and C4_4S: Microwave Spectral Taxonomy as a Stepping Stone to the Millimeter-Wave Band

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    We present a microwave spectral taxonomy study of several hydrocarbon/CS2_2 discharge mixtures in which more than 60 distinct chemical species, their more abundant isotopic species, and/or their vibrationally excited states were detected using chirped-pulse and cavity Fourier-transform microwave spectroscopies. Taken together, in excess of 85 unique variants were detected, including several new isotopic species and more than 25 new vibrationally excited states of C2_2S, C3_3S, and C4_4S, which have been assigned on the basis of published vibration-rotation interaction constants for C3_3S, or newly calculated ones for C2_2S and C4_4S. On the basis of these precise, low-frequency measurements, several vibrationally exited states of C2_2S and C3_3S were subsequently identified in archival millimeter-wave data in the 253--280 GHz frequency range, ultimately providing highly accurate catalogs for astronomical searches. As part of this work, formation pathways of the two smaller carbon-sulfur chains were investigated using 13^{13}C isotopic spectroscopy, as was their vibrational excitation. The present study illustrates the utility of microwave spectral taxonomy as a tool for complex mixture analysis, and as a powerful and convenient `stepping stone' to higher frequency measurements in the millimeter and submillimeter bands.Comment: Accepted in PCC

    Inhibition of the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl- ʟ, ʟ-diaminopimelic Acid Desuccinylase from \u3cem\u3eNeisseria meningitidis\u3c/em\u3e by ʟ-Captopril

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    Binding of the competitive inhibitor ʟ-captopril to the dapE-encoded N-succinyl-ʟ, ʟ-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. ʟ-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. ʟ-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of the interaction of ʟ-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with ʟ-captopril at 1.8 Å resolution. Combination of these data provides new insights into binding of ʟ-captopril to the active site of DapE enzymes as well as important inhibitor–active site residue interaction’s. Such information is critical for the design of new, potent inhibitors of DapE enzymes

    Statin use and adverse effects among adults \u3e 75 years of age: Insights from the Patient and Provider Assessment of Lipid Management (PALM) registry

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    Background: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and results: We compared statin use and dosing between adults \u3e75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were \u3e75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those \u3e75 years old versus 63.1% in those ≤75 years old (P=0.83); high-dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [P=0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [PP=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; Conclusions: Overall use of statins was similar for primary prevention in those aged \u3e75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adult

    Patient-reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry

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    Background: Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation.Methods and Results: This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin.Conclusions: More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered

    Characterizing the pre-clinical phase of inflammatory bowel disease

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    Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn's disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnostic phase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset-obtained from the Danish registers-we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.</p
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