Auditor Type and Audit Quality Differences in Nonprofit Healthcare Organizations – U.S. Evidence

The purpose of this paper is to explore audit quality in nonprofit healthcare organizations by investigating differences in audit report outcomes. Specifically, we examine the relationship between auditor type and auditor-disclosed internal control exceptions in Circular A-133 audits of U.S. nonprofit healthcare organizations. Our findings indicate audits of nonprofit healthcare organizations conducted by the Big Four CPA firms carry a lower likelihood of disclosing internal control exceptions (i.e., reportable conditions and material weaknesses) than are audits conducted by smaller CPA firms. This challenges the general contention from prior studies that the Big Four firms are better audit quality providers and indicates that the alleged superiority of Big Four firms in terms of audit quality may not be generalizable to all industry sectors.Audit quality, Auditor type, Circular A-133, Nonprofit healthcare, Single Audit Act

Local cytokine transcription in naïve and previously infected sheep and lambs following challenge with Teladorsagia circumcincta

<b>Background</b><p></p> The abomasal helminth Teladorsagia circumcincta is one of the most economically important parasites affecting sheep in temperate regions. Infection is particularly detrimental to lambs, in which it can cause pronounced morbidity and severe production losses. Due to the spreading resistance of this parasite to all classes of anthelmintic drugs, teladorsagiosis is having an increasingly severe impact on the sheep industry with significant implications for sheep welfare. Protective immunity develops slowly, wanes rapidly and does not appear to be as effective in young lambs. To investigate the development of immunity to T. circumcincta in sheep and lambs, we used cytokine transcript profiling to examine differences in the abomasal mucosa and gastric lymph node of naïve and previously infected sheep and lambs following challenge.<p></p> <b>Results</b><p></p> The results of these experiments demonstrated that the abomasal mucosa is a major source of cytokines during abomasal helminth infection. A local Th2-type cytokine response was observed in the abomasal mucosa and gastric lymph node of the previously infected sheep and lambs when compared with those of the naïve during the early stages of infection. In contrast, a pro-inflammatory component more was evident in the abomasal mucosa and gastric lymph node of the naïve sheep when compared with those of the previously infected, which was not observed in the lambs.<p></p> <b>Conclusions</b><p></p> The greater levels of Th2-type cytokine transcripts in both the abomasum and gastric lymph node of the previously infected compared with naïve sheep and lambs emphasises the importance of these mechanisms in the immune response to T. circumcincta infection. Younger lambs appear to be able to generate similar Th2-type responses in the abomasum suggesting that the increased morbidity and apparent lack of resistance in younger lambs following continuous or repeated exposure to T. circumcincta is unlikely to be due to a lack of appropriate Th2-type cytokine production

Parallel and Sequential Pathways of Molecular Recognition of a Tandem-Repeat Protein and Its Intrinsically Disordered Binding Partner.

The Wnt signalling pathway plays an important role in cell proliferation, differentiation, and fate decisions in embryonic development and the maintenance of adult tissues. The twelve armadillo (ARM) repeat-containing protein β-catenin acts as the signal transducer in this pathway. Here, we investigated the interaction between β-catenin and the intrinsically disordered transcription factor TCF7L2, comprising a very long nanomolar-affinity interface of approximately 4800 Å2 that spans ten of the twelve ARM repeats of β-catenin. First, a fluorescence reporter system for the interaction was engineered and used to determine the kinetic rate constants for the association and dissociation. The association kinetics of TCF7L2 and β-catenin were monophasic and rapid (7.3 ± 0.1 × 107 M-1·s-1), whereas dissociation was biphasic and slow (5.7 ± 0.4 × 10-4 s-1, 15.2 ± 2.8 × 10-4 s-1). This reporter system was then combined with site-directed mutagenesis to investigate the striking variability in the conformation adopted by TCF7L2 in the three different crystal structures of the TCF7L2-β-catenin complex. We found that the mutation had very little effect on the association kinetics, indicating that most interactions form after the rate-limiting barrier for association. Mutations of the N- and C-terminal subdomains of TCF7L2 that adopt relatively fixed conformations in the crystal structures had large effects on the dissociation kinetics, whereas the mutation of the labile sub-domain connecting them had negligible effect. These results point to a two-site avidity mechanism of binding with the linker region forming a "fuzzy" complex involving transient contacts that are not site-specific. Strikingly, the two mutations in the N-terminal subdomain that had the largest effects on the dissociation kinetics showed two additional phases, indicating partial flux through an alternative dissociation pathway that is inaccessible to the wild type. The results presented here provide insights into the kinetics of the molecular recognition of a long intrinsically disordered region with an elongated repeat-protein surface, a process found to involve parallel routes with sequential steps in each

Structure, function, and assembly of heme centers in mitochondrial respiratory complexes

The sequential flow of electrons in the respiratory chain, from a low reduction potential substrate to O2, is mediated by protein-bound redox cofactors. In mitochondria, hemes—together with flavin, iron–sulfur, and copper cofactors—mediate this multi-electron transfer. Hemes, in three different forms, are used as a protein-bound prosthetic group in succinate dehydrogenase (complex II), in bc1 complex (complex III) and in cytochrome c oxidase (complex IV). The exact function of heme b in complex II is still unclear, and lags behind in operational detail that is available for the hemes of complex III and IV. The two b hemes of complex III participate in the unique bifurcation of electron flow from the oxidation of ubiquinol, while heme c of the cytochrome c subunit, Cyt1, transfers these electrons to the peripheral cytochrome c. The unique heme a3, with CuB, form a catalytic site in complex IV that binds and reduces molecular oxygen. In addition to providing catalytic and electron transfer operations, hemes also serve a critical role in the assembly of these respiratory complexes, which is just beginning to be understood. In the absence of heme, the assembly of complex II is impaired, especially in mammalian cells. In complex III, a covalent attachment of the heme to apo-Cyt1 is a prerequisite for the complete assembly of bc1, whereas in complex IV, heme a is required for the proper folding of the Cox 1 subunit and subsequent assembly. In this review, we provide further details of the aforementioned processes with respect to the hemes of the mitochondrial respiratory complexes

Structure, function, and assembly of heme centers in mitochondrial respiratory complexes

The sequential flow of electrons in the respiratory chain, from a low reduction potential substrate to O2, is mediated by protein-bound redox cofactors. In mitochondria, hemes—together with flavin, iron–sulfur, and copper cofactors—mediate this multi-electron transfer. Hemes, in three different forms, are used as a protein-bound prosthetic group in succinate dehydrogenase (complex II), in bc1 complex (complex III) and in cytochrome c oxidase (complex IV). The exact function of heme b in complex II is still unclear, and lags behind in operational detail that is available for the hemes of complex III and IV. The two b hemes of complex III participate in the unique bifurcation of electron flow from the oxidation of ubiquinol, while heme c of the cytochrome c subunit, Cyt1, transfers these electrons to the peripheral cytochrome c. The unique heme a3, with CuB, form a catalytic site in complex IV that binds and reduces molecular oxygen. In addition to providing catalytic and electron transfer operations, hemes also serve a critical role in the assembly of these respiratory complexes, which is just beginning to be understood. In the absence of heme, the assembly of complex II is impaired, especially in mammalian cells. In complex III, a covalent attachment of the heme to apo-Cyt1 is a prerequisite for the complete assembly of bc1, whereas in complex IV, heme a is required for the proper folding of the Cox 1 subunit and subsequent assembly. In this review, we provide further details of the aforementioned processes with respect to the hemes of the mitochondrial respiratory complexes

Será que a dosagem na educação para a abstinência faz a diferença?

Although past reviews uniformly criticized the efficacy and effectiveness of sexual abstinence in adolescents, new studies dispute the earlier findings. Studies that unpackage intervention programs provide one means of understanding why they succeed in some settings and not in others. This study examined 3183 students spread over 35 schools on the number of hours that they received in sexual abstinence education, in a context of health behaviors promotion. A multi-level analysis (HLM) was performed. The number of hours did not appear to make any difference in the outcome scores. Reasons for this finding are presented and their implications are provided.Embora a literatura duma forma generalizada tenha uniformemente criticado a eficácia dos programas de abstinência sexual em adolescentes, novos estudos parecem contestar os resultados iniciais. Estudos que descompactam os programas de intervenção fornecem um meio de entender por que os programas de abstinência podem ter sucesso em alguns contextos e não em outros. Este estudo analisou 3.183 alunos distribuídos por 35 escolas sobre o número de horas que eles receberam em educação para a abstinência sexual, num contexto de promoção de comportamentos saudáveis. Foi realizada uma análise multi-level (HLM). O número de horas não pareceu fazer diferença nos resultados obtidos. As razões para esta conclusão são apresentados e suas implicações são fornecidas

Modeling abstinence education effectiveness

Background: Controversy about the effectiveness of abstinence education has posed troubling dilemmas for everyone involved in this area of study. Strident statements about the lack of efficacy of abstinence education have approached the level of bitter ideology. One remedy to lessen this focus on ideology is to provide a broader analysis of program efforts. Method: This paper provides an innovative analysis of a community-based abstinence education program that encompassed multiple schools across several counties that includes thousands of students. The design addressed many deficits in published studies; it used hierarchical linear modeling to remedy the design flaws of a simple pretest-posttest analysis. Results: Pretests were the principal predictors of posttest scores. Gender was also a significant predictor of posttest scores. Age however was not a significant predictor. An interaction between gender and age was a significant predictor although a three-way interaction of gender x age x race was not. Conclusion: Implications for the findings are stated with recommendations for further research

A Digital Neuromorphic Architecture Efficiently Facilitating Complex Synaptic Response Functions Applied to Liquid State Machines

Information in neural networks is represented as weighted connections, or synapses, between neurons. This poses a problem as the primary computational bottleneck for neural networks is the vector-matrix multiply when inputs are multiplied by the neural network weights. Conventional processing architectures are not well suited for simulating neural networks, often requiring large amounts of energy and time. Additionally, synapses in biological neural networks are not binary connections, but exhibit a nonlinear response function as neurotransmitters are emitted and diffuse between neurons. Inspired by neuroscience principles, we present a digital neuromorphic architecture, the Spiking Temporal Processing Unit (STPU), capable of modeling arbitrary complex synaptic response functions without requiring additional hardware components. We consider the paradigm of spiking neurons with temporally coded information as opposed to non-spiking rate coded neurons used in most neural networks. In this paradigm we examine liquid state machines applied to speech recognition and show how a liquid state machine with temporal dynamics maps onto the STPU-demonstrating the flexibility and efficiency of the STPU for instantiating neural algorithms.Comment: 8 pages, 4 Figures, Preprint of 2017 IJCN

Integration of the CMS regional calorimeter Trigger hardware into the CMS level-1 Trigger

The electronics for the Regional Calorimeter Trigger (RCT) of the Compact Muon Solenoid Experiment (CMS) have been produced and tested. The RCT hardware consists of 18 double-sided crates containing custom boards, ASICs, and backplanes. The RCT receives 8-bit energies and a data quality bit from the HCAL and ECAL Trigger Primitive Generators (TPGs) and sends it to the CMS Global Calorimeter Trigger (GCT) after processing. Before installation, integration tests were performed. Data was successfully received from the TPG electronics and read out with a RCT Jet Capture Card. These tests, other tests involving more trigger subsystems, their results, and the RCT installation will be described

Late-Stage Maturation of the Rieske Fe/S Protein: Mzm1 Stabilizes Rip1 but Does Not Facilitate Its Translocation by the AAA ATPase Bcs1

The final step in the assembly of the ubiquinol-cytochrome c reductase or bc1 complex involves the insertion of the Rieske Fe/S cluster protein, Rip1. Maturation of Rip1 occurs within the mitochondrial matrix prior to its translocation across the inner membrane (IM) in a process mediated by the Bcs1 ATPase and subsequent insertion into the bc1 complex. Here we show that the matrix protein Mzm1 functions as a Rip1 chaperone, stabilizing Rip1 prior to the translocation step. In the absence of Mzm1, Rip1 is prone to either proteolytic degradation or temperature-induced aggregation. A series of Rip1 truncations were engineered to probe motifs necessary for Mzm1 interaction and Bcs1-mediated translocation of Rip1. The Mzm1 interaction with Rip1 persists in Rip1 variants lacking its transmembrane domain or containing only its C-terminal globular Fe/S domain. Replacement of the globular domain of Rip1 with that of the heterologous folded protein Grx3 abrogated Mzm1 interaction; however, appending the C-terminal 30 residues of Rip1 to the Rip1-Grx3 chimera restored Mzm1 interaction. The Rip1-Grx3 chimera and a Rip1 truncation containing only the N-terminal 92 residues each induced stabilization of the bc1:cytochrome oxidase supercomplex in a Bcs1-dependent manner. However, the Rip1 variants were not stably associated with the supercomplex. The induced supercomplex stabilization by the Rip1 N terminus was independent of Mzm1