Sales tax enforcement: An empirical analysis of compliance enforcement methodologies and pathologies

Most research on tax evasion has focused on the income tax. Sales tax evasion has been largely ignored and dismissed as immaterial. This paper explored the differences between income tax and sales tax evasion and demonstrated that sales tax enforcement is deserving of and requires the use of different tools to achieve compliance. Specifically, the major enforcement problem with sales tax is not evasion: it is theft perpetrated by companies that act as collection agents for the state. Companies engage in a principal-agent relationship with the state and many retain funds collected as an agent of the state for private use. As such, the act of sales tax theft bears more resemblance to embezzlement than to income tax evasion. It has long been assumed that the sales tax is nearly evasion free, and state revenue departments report voluntary compliance in a manner that perpetuates this myth. Current sales tax compliance enforcement methodologies are similar in form to income tax compliance enforcement methodologies and are based largely on trust. The primary focus is on delinquent filers with a very small percentage of businesses subject to audit. As a result, there is a very large group of noncompliant businesses who file on time and fly below the radar while stealing millions of taxpayer dollars. ^ The author utilized a variety of statistical methods with actual field data derived from operations of the Southern Region Criminal Investigations Unit of the Florida Department of Revenue to evaluate current and proposed sales tax compliance enforcement methodologies in a quasi-experimental, time series research design and to set forth a typology of sales tax evaders. This study showed that current estimates of voluntary compliance in sales tax systems are seriously and significantly overstated and that current enforcement methodologies are inadequate to identify the majority of violators and enforce compliance. Sales tax evasion is modeled using the theory of planned behavior and Cressey’s fraud triangle and it is demonstrated that proactive enforcement activities, characterized by substantial contact with non-delinquent taxpayers, results in superior ability to identify noncompliance and provides a structure through which noncompliant businesses can be rehabilitated.^

Thioredoxin and Jab1 control estrogen- and antiestrogen-mediated progression of the cell cycle through p27 interactions

A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and protein-protein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

A generic model of execution for synthesizing domain-specific models

Software engineering researchers are challenged to provide increasingly more powerful levels of abstractions to address the rising complexity inherent in software solutions. One new development paradigm that places models as abstraction at the forefront of the development process is Model-Driven Software Development (MDSD). MDSD considers models as first class artifacts, extending the capability for engineers to use concepts from the problem domain of discourse to specify apropos solutions. A key component in MDSD is domain-specific modeling languages (DSMLs) which are languages with focused expressiveness, targeting a specific taxonomy of problems. The de facto approach used is to first transform DSML models to an intermediate artifact in a HLL e.g., Java or C++, then execute that resulting code.^ Our research group has developed a class of DSMLs, referred to as interpreted DSMLs (i-DSMLs), where models are directly interpreted by a specialized execution engine with semantics based on model changes at runtime. This execution engine uses a layered architecture and is referred to as a domain-specific virtual machine (DSVM). As the domain-specific model being executed descends the layers of the DSVM the semantic gap between the user-defined model and the services being provided by the underlying infrastructure is closed. The focus of this research is the synthesis engine, the layer in the DSVM which transforms i-DSML models into executable scripts for the next lower layer to process.^ The appeal of an i-DSML is constrained as it possesses unique semantics contained within the DSVM. Existing DSVMs for i-DSMLs exhibit tight coupling between the implicit model of execution and the semantics of the domain, making it difficult to develop DSVMs for new i-DSMLs without a significant investment in resources.^ At the onset of this research only one i-DSML had been created for the user- centric communication domain using the aforementioned approach. This i-DSML is the Communication Modeling Language (CML) and its DSVM is the Communication Virtual machine (CVM). A major problem with the CVM's synthesis engine is that the domain-specific knowledge (DSK) and the model of execution (MoE) are tightly interwoven consequently subsequent DSVMs would need to be developed from inception with no reuse of expertise.^ This dissertation investigates how to decouple the DSK from the MoE and subsequently producing a generic model of execution (GMoE) from the remaining application logic. This GMoE can be reused to instantiate synthesis engines for DSVMs in other domains. The generalized approach to developing the model synthesis component of i-DSML interpreters utilizes a reusable framework loosely coupled to DSK as swappable framework extensions.^ This approach involves first creating an i-DSML and its DSVM for a second do- main, demand-side smartgrid, or microgrid energy management, and designing the synthesis engine so that the DSK and MoE are easily decoupled. To validate the utility of the approach, the SEs are instantiated using the GMoE and DSKs of the two aforementioned domains and an empirical study to support our claim of reduced developmental effort is performed.^

Management of remote field instrumentation via the Internet

Supervisory Control & Data Acquisition (SCADA) systems are used by many industries because of their ability to manage sensors and control external hardware. The problem with commercially available systems is that they are restricted to a local network of users that use proprietary software. There was no Internet development guide to give remote users out of the network, control and access to SCADA data and external hardware through simple user interfaces. To solve this problem a server/client paradigm was implemented to make SCADAs available via the Internet. Two methods were applied and studied: polling of a text file as a low-end technology solution and implementing a Transmission Control Protocol (TCP/IP) socket connection. Users were allowed to login to a website and control remotely a network of pumps and valves interfaced to a SCADA. This enabled them to sample the water quality of different reservoir wells. The results were based on real time performance, stability and ease of use of the remote interface and its programming. These indicated that the most feasible server to implement is the TCP/IP connection. For the user interface, Java applets and Active X controls provide the same real time access.

Rede de atendimento socioeducativo: possibilidades e limites da garantia de direitos

The results of the research systematized on this analysis sought apprehend the linkage of the socio-educational service network, destined to adolescents who comply with socioeducational measure of confinement, in the region of the Seridó of the state of the Rio Grande do Norte, especially in the city of Caicó, central town of this region. The achievement of this study was stimulated by the interest in unraveling the contradictory reality imposed by neoliberal State, sparing the guarantee of rights, especially to these teens, who are seen as authors of violations and are stigmatized by capitalist society. The research was carried in the period July-September 2013, under critical perspective, using the documental analysis and the observational techniques and interviews with professionals of the Educational Center (CEDUC), of the Unified Health System (SUS), of the Social Policies of Social Assistance, and of the State Department of Education, which should make the service network that gravitates around the National System of Socio-educational Services (SINASE). The Statute of Children and Adolescents (ECA) and SINASE define that the application of socioeducational measures cannot occur isolated of the public policies, becoming indispensable the linkages of the system with the social policies of social assistance, education and health. However, it was observed that the neoliberal logic of the capitalist State has developed broken, disconnected, focal and superficial social policies, who fail give effect to the rights acquired beyond the legal sphere. In this perspective, it is possible affirm that the everyday of the Brazilian poor teens is marked by the action of the State, which aims to control those who disturb the order of capital, who threaten the production, the market, the consume and the private property. This way, actions are promoted criminalizing poverty and imprint a legal action over this expression of the social issue to the detriment of social policies that meet the real needs of adolescents. Face of this reality, it becomes necessary to put on the agenda of the here and now to fight for rights, aiming at a broad public debate involving professionals, researchers and social movements in support of the viability of rights, which aims to support reflections and to strengthen ways to confront this social problem. With the approximations of this study, it was learned that the struggle for rights is a fight for another project of society, beyond what is laid.

Desenvolvimento da célula base de microestruturas periódicas de compósitos sob otimização topológica

This thesis develops a new technique for composite microstructures projects by the Topology Optimization process, in order to maximize rigidity, making use of Deformation Energy Method and using a refining scheme h-adaptative to obtain a better defining the topological contours of the microstructure. This is done by distributing materials optimally in a region of pre-established project named as Cell Base. In this paper, the Finite Element Method is used to describe the field and for government equation solution. The mesh is refined iteratively refining so that the Finite Element Mesh is made on all the elements which represent solid materials, and all empty elements containing at least one node in a solid material region. The Finite Element Method chosen for the model is the linear triangular three nodes. As for the resolution of the nonlinear programming problem with constraints we were used Augmented Lagrangian method, and a minimization algorithm based on the direction of the Quasi-Newton type and Armijo-Wolfe conditions assisting in the lowering process. The Cell Base that represents the composite is found from the equivalence between a fictional material and a preescribe material, distributed optimally in the project area. The use of the strain energy method is justified for providing a lower computational cost due to a simpler formulation than traditional homogenization method. The results are presented prescription with change, in displacement with change, in volume restriction and from various initial values of relative densities.

Qualidade de vida de pessoas com estomias intestinais

Ostomy is an open surgical origin, when it is necessary to deviate temporarily or permanently, the normal transit of food and / or deletions. The patient with ostomy disposal is faced with changes in their physiology, also emerging on the need to care collection bag. This study aimed to analyze the quality of life (QOL) of people living with ostomy Intestinal (EI), who attended the Pediatric and Adult Rehabilitation Center of Rio Grande do Norte (CRI / CRA-RN). It is an analytical study with cross-sectional design and quantitative approach, accomplished with 89 people who had EI. The study was approved by the Ethics Committee of the Federal University of Rio Grande do Norte (CEP / UFRN), CAAE: 19866413.3.0000.5537. Held data collection in the period January-March 2015 using two instruments: an adapted general questionnaire covering socio-demographic, clinical and self-care and a specific instrument for assessing QOL of people with stoma titled as City of Hope Quality of Life - Ostomy Questionnaire (COH-QOL-Q), validated and adapted to Portuguese in 2010, composed of four areas, namely: Welfare Body (BEF), Welfare Psychological (BEP), Welfare (BES ) and Spiritual Well-Being (BEE). The collected data were entered into a database in Microsoft Excel 2007 spreadsheet application and processed in computerized software for descriptive and inferential analysis. The results showed that 83.1% had a colostomy and ileostomy 16.9%. Sociodemographic characteristics prevailed in males (57.3%), over 50 (57.3%), mulatto (46.1%), with presence of companion / a (57.3%), retired / beneficiaries (50.5%), monthly income above the minimum wage (68.5%) and who have studied up to elementary school (67.4%). Regarding clinical aspects, it was observed that the main cause that led to the making of the stoma was the neoplasm (59.6%) followed by trauma (21.3%). The sample showed people with stoma for more than six months (79.8%) of permanently (57.3%), in use sink equipment piece drainable (68.5%) of flat base (82.0%). With respect to self-care, 93.3% emptied and washed the bag alone (care related to hygiene) and 75.3% fixed the new exchange on the skin during the exchange (care related to the stock). Patients with more than six months of ostomy and had no partner (a) had higher averages of self-care related hygiene and purse. The average of respondents QoL scores was 68.90% for General QOL; 68.03% for the BEF; 68.38% for the BEP; 66.46% for BES and 75.41% for BEE. Among the aspects that influenced QOL included: physical strength, pain, suffering and gases (physical domain); appearance, care of the stoma and adaptation to new condition (psychological domain); isolation, interference in personal relationships and social activities (social domain) and going to church or synagogue, spiritual activities and positive change after ostomy (spiritual realm). Based on these results, it is concluded that this was a predominantly adult sample / elderly (between 50 and 70 years), with low education and the cause motivating the stoma, neoplasms. However, such findings did not pass at low percentage levels on the self-care capacity to deliver even at low QOL scores.

Qualidade de vida de pessoas com estomias intestinais

Ostomy is an open surgical origin, when it is necessary to deviate temporarily or permanently, the normal transit of food and / or deletions. The patient with ostomy disposal is faced with changes in their physiology, also emerging on the need to care collection bag. This study aimed to analyze the quality of life (QOL) of people living with ostomy Intestinal (EI), who attended the Pediatric and Adult Rehabilitation Center of Rio Grande do Norte (CRI / CRA-RN). It is an analytical study with cross-sectional design and quantitative approach, accomplished with 89 people who had EI. The study was approved by the Ethics Committee of the Federal University of Rio Grande do Norte (CEP / UFRN), CAAE: 19866413.3.0000.5537. Held data collection in the period January-March 2015 using two instruments: an adapted general questionnaire covering socio-demographic, clinical and self-care and a specific instrument for assessing QOL of people with stoma titled as City of Hope Quality of Life - Ostomy Questionnaire (COH-QOL-Q), validated and adapted to Portuguese in 2010, composed of four areas, namely: Welfare Body (BEF), Welfare Psychological (BEP), Welfare (BES ) and Spiritual Well-Being (BEE). The collected data were entered into a database in Microsoft Excel 2007 spreadsheet application and processed in computerized software for descriptive and inferential analysis. The results showed that 83.1% had a colostomy and ileostomy 16.9%. Sociodemographic characteristics prevailed in males (57.3%), over 50 (57.3%), mulatto (46.1%), with presence of companion / a (57.3%), retired / beneficiaries (50.5%), monthly income above the minimum wage (68.5%) and who have studied up to elementary school (67.4%). Regarding clinical aspects, it was observed that the main cause that led to the making of the stoma was the neoplasm (59.6%) followed by trauma (21.3%). The sample showed people with stoma for more than six months (79.8%) of permanently (57.3%), in use sink equipment piece drainable (68.5%) of flat base (82.0%). With respect to self-care, 93.3% emptied and washed the bag alone (care related to hygiene) and 75.3% fixed the new exchange on the skin during the exchange (care related to the stock). Patients with more than six months of ostomy and had no partner (a) had higher averages of self-care related hygiene and purse. The average of respondents QoL scores was 68.90% for General QOL; 68.03% for the BEF; 68.38% for the BEP; 66.46% for BES and 75.41% for BEE. Among the aspects that influenced QOL included: physical strength, pain, suffering and gases (physical domain); appearance, care of the stoma and adaptation to new condition (psychological domain); isolation, interference in personal relationships and social activities (social domain) and going to church or synagogue, spiritual activities and positive change after ostomy (spiritual realm). Based on these results, it is concluded that this was a predominantly adult sample / elderly (between 50 and 70 years), with low education and the cause motivating the stoma, neoplasms. However, such findings did not pass at low percentage levels on the self-care capacity to deliver even at low QOL scores.

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.

Influência da utilização do fluido de corte com adição de grafeno na temperatura de usinagem e formação de rebarba no processo de micro fresamento

As time passed, humanity needed the development of new materials used in various activities. High strength materials such as titanium and Inconel for example, had been studied because they are widely used for implants in biomedicine, as well as their use in aerospace and automotive industries. Because of its thermal and mechanical properties, these materials are considered difficult to machine, promoting a rapid wear of cutting tools, primarily caused by the high temperatures in machining. With the development of new materials has emerged the need of developing new manufacturing processes. One of today’s innovative processes is the micro-manufacturing. Being a process with a defined cutting tool geometry, burr formation is a constant and undesirable phenomenon formed during the machininig process. Being detrimental to the manufacturing process, overspending deburring operations are constantly employed leading to increase the aggregate cost to the manufactured material. Assembly components are also impaired if there is no control of the burr, with consequences including the disposal of components due to the occurence of this phenomenon. This paper presents the study of micro-milling Inconel 718, investigating influential parameters in the formation of burrs in order to minimize the occurrence of this phenome non. Different feed rates per tooth and cutting speed are evaluated, and different cutting fluids with different methods of applying the fluid. Adding graphene to cutting fluids was considered as a variable to be investigated, which is considered an excellent solid lubricant, in addition to increasing the thermal conductivity of the cooling solution (AZIMI; MOZAF FARI, 2015). The micro-milling temperature was evaluated in the present work. It was observed a new phenomenon that causes the machined surface temperature decreases below room temperature when using the solution water + oil. This phenomenon is explained in further chapters. In order to unravel this phenomenon, a new test was proposed and, from this test, it can be concluded, comparatively, which cutting fluid has a better cooling property.Using cutting fluid with different thermal properties has shown influence when analy zing burr formation and reducing machining temperature.

Noção de simetria na cosmologia de Anaximandro de Mileto

Through the philosophical movements in Ionia and through researches made on phýsis (started by the first wise men in Miletus), we elected Anaximander‟s cosmology as a fertile ground for exploring the Greek notion of symmetry. From a geographical perspective, initially, the Greeks‟ originality towards the notion of a due measure will be questioned, since the astrological and mathematical knowledge were common in Babylon and Egypt. Although the cultural environment on the Milesian commercial ports and its architecture show evidences of a possible eastern impact on the Greek thought, it will be noted (from fragments validated by the Doxography tradition) that the problem with the birthplace of the notion of harmony and of due measure is something specific of the Greek culture and inherent to its remote religiosity. The resumption of these notions refers to the issue of arché and to its divinity assumed by Thales, Anaximander and Anaximenes. The divine was not an extrinsic notion to the Milesian thought towards the first element. Therefore, we will have as a result of this investigation some assumptions for which the notion of symmetry in Anaximander, stated in his ápeiron, could be, from the dialogue between philosophy and Orphism, an assimilation of the One, as witnessed in the Derveni papyrus.

The evolutionary relationships and age of Homo naledi : an assessment using dated Bayesian phylogenetic methods

Acknowledgements We wish to express our gratitude to the National Geographic Society and the National Research Foundation of South Africa for funding the discovery, recovery, and analysis of the H. naledi material. The study reported here was also made possible by grants from the Social Sciences and Humanities Research Council of Canada, the Canada Foundation for Innovation, the British Columbia Knowledge Development Fund, the Canada Research Chairs Program, Simon Fraser University, the DST/NRF Centre of Excellence in Palaeosciences (COE-Pal), as well as by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada, a Young Scientist Development Grant from the Paleontological Scientific Trust (PAST), a Baldwin Fellowship from the L.S.B. Leakey Foundation, and a Seed Grant and a Cornerstone Faculty Fellowship from the Texas A&M University College of Liberal Arts. We would like to thank the South African Heritage Resource Agency for the permits necessary to work on the Rising Star site; the Jacobs family for granting access; Wilma Lawrence, Bonita De Klerk, Merrill Van der Walt, and Justin Mukanku for their assistance during all phases of the project; Lucas Delezene for valuable discussion on the dental characters of H. naledi. We would also like to thank Peter Schmid for the preparation of the Dinaledi fossil material; Yoel Rak for explaining in detail some of the characters used in previous studies; William Kimbel for drawing our attention to the possibility that there might be a problem with Dembo et al.’s (2015) codes for the two characters related to the articular eminence; Will Stein for helpful discussion about the Bayesian analyses; Mike Lee for his comments on this manuscript; John Hawks for his support in organizing the Rising Star workshop; and the associate editor and three anonymous reviewers for their valuable comments. We are grateful to S. Potze and the Ditsong Museum, B. Billings and the School of Anatomical Sciences at the University of the Witwatersrand, and B. Zipfel and the Evolutionary Studies Institute at the University of the Witwatersrand for providing access to the specimens in their care; the University of the Witwatersrand, the Evolutionary Studies Institute, and the South African National Centre of Excellence in PalaeoSciences for hosting a number of the authors while studying the material; and the Western Canada Research Grid for providing access to the high-performance computing facilities for the Bayesian analyses. Last but definitely not least, we thank the head of the Rising Star project, Lee Berger, for his leadership and support, and for encouraging us to pursue the study reported here.

Stimulus Integration and Parsing in the Primate Auditory Midbrain

Integrating information from multiple sources is a crucial function of the brain. Examples of such integration include multiple stimuli of different modalties, such as visual and auditory, multiple stimuli of the same modality, such as auditory and auditory, and integrating stimuli from the sensory organs (i.e. ears) with stimuli delivered from brain-machine interfaces.

The overall aim of this body of work is to empirically examine stimulus integration in these three domains to inform our broader understanding of how and when the brain combines information from multiple sources.

First, I examine visually-guided auditory, a problem with implications for the general problem in learning of how the brain determines what lesson to learn (and what lessons not to learn). For example, sound localization is a behavior that is partially learned with the aid of vision. This process requires correctly matching a visual location to that of a sound. This is an intrinsically circular problem when sound location is itself uncertain and the visual scene is rife with possible visual matches. Here, we develop a simple paradigm using visual guidance of sound localization to gain insight into how the brain confronts this type of circularity. We tested two competing hypotheses. 1: The brain guides sound location learning based on the synchrony or simultaneity of auditory-visual stimuli, potentially involving a Hebbian associative mechanism. 2: The brain uses a ‘guess and check’ heuristic in which visual feedback that is obtained after an eye movement to a sound alters future performance, perhaps by recruiting the brain’s reward-related circuitry. We assessed the effects of exposure to visual stimuli spatially mismatched from sounds on performance of an interleaved auditory-only saccade task. We found that when humans and monkeys were provided the visual stimulus asynchronously with the sound but as feedback to an auditory-guided saccade, they shifted their subsequent auditory-only performance toward the direction of the visual cue by 1.3-1.7 degrees, or 22-28% of the original 6 degree visual-auditory mismatch. In contrast when the visual stimulus was presented synchronously with the sound but extinguished too quickly to provide this feedback, there was little change in subsequent auditory-only performance. Our results suggest that the outcome of our own actions is vital to localizing sounds correctly. Contrary to previous expectations, visual calibration of auditory space does not appear to require visual-auditory associations based on synchrony/simultaneity.

My next line of research examines how electrical stimulation of the inferior colliculus influences perception of sounds in a nonhuman primate. The central nucleus of the inferior colliculus is the major ascending relay of auditory information before it reaches the forebrain, and thus an ideal target for understanding low-level information processing prior to the forebrain, as almost all auditory signals pass through the central nucleus of the inferior colliculus before reaching the forebrain. Thus, the inferior colliculus is the ideal structure to examine to understand the format of the inputs into the forebrain and, by extension, the processing of auditory scenes that occurs in the brainstem. Therefore, the inferior colliculus was an attractive target for understanding stimulus integration in the ascending auditory pathway.

Moreover, understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n=172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals’ judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site in comparison to the reference frequency employed in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site’s response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated and provide a greater range of evoked percepts.

My next line of research employs a frequency-tagging approach to examine the extent to which multiple sound sources are combined (or segregated) in the nonhuman primate inferior colliculus. In the single-sound case, most inferior colliculus neurons respond and entrain to sounds in a very broad region of space, and many are entirely spatially insensitive, so it is unknown how the neurons will respond to a situation with more than one sound. I use multiple AM stimuli of different frequencies, which the inferior colliculus represents using a spike timing code. This allows me to measure spike timing in the inferior colliculus to determine which sound source is responsible for neural activity in an auditory scene containing multiple sounds. Using this approach, I find that the same neurons that are tuned to broad regions of space in the single sound condition become dramatically more selective in the dual sound condition, preferentially entraining spikes to stimuli from a smaller region of space. I will examine the possibility that there may be a conceptual linkage between this finding and the finding of receptive field shifts in the visual system.

In chapter 5, I will comment on these findings more generally, compare them to existing theoretical models, and discuss what these results tell us about processing in the central nervous system in a multi-stimulus situation. My results suggest that the brain is flexible in its processing and can adapt its integration schema to fit the available cues and the demands of the task.

Evaluating the Impact of the Positive Choices Intervention on Substance Use, Psychological, and Care Engagement Outcomes Relevant to Current National HIV Prevention Goals

The HIV epidemic in the United States continues to be a significant public health problem, with approximately 50,000 new infections occurring each year. National public health priorities have shifted in recent years towards targeted HIV prevention efforts among people living with HIV/AIDS (PLWHA) that include: increasing engagement in and retention in care, improving HIV treatment adherence, and increasing screening for and treatment of substance use and psychological difficulties. This study evaluated the efficacy of Positive Choices (PC), a brief, care-based, theory-driven, 3-session counseling intervention for newly HIV-diagnosed men who have sex with men (MSM), in the context of current national HIV prevention priorities. The study involved secondary analysis of data from a preliminary efficacy trial of the PC intervention (n=102). Descriptive statistics examined baseline substance use, psychological characteristics and strategies, and care engagement and HIV-related biological outcomes. Generalized Estimating Equations (GEE) examined longitudinal changes in these variables by study condition. Results indicated that PC improved adherence to HIV treatment, but increased use of illicit drugs, specifically amyl nitrates and other stimulant drugs; additionally, moderation analyses indicated differences in patterns of change over time in viral load by baseline depression status. Implications of the findings and suggestions for future research are discussed.