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Self-generated touches to the body or supporting surface are considered important contributors to the emergence of an early sense of the body and self in infancy. Both are critical for the formation of later goal-directed actions. Very few studies have examined in detail the development of these early spontaneous touches during the first months of life. In this study, we followed weekly four infants in two naturalistic 5-minute sessions (baseline and toys-in-view) as they laid alert in supine from the age of 3 weeks until they acquired head control. We found that throughout the two months of observation, infants engaged in a high rate of touch and spent about 50 percent of the time moving their hands from one touch location to the next. On most sessions, they produced up to 200 body/surface contacts and touched as many as 18 different areas (mainly upper body and floor) with each hand. When we did not consider the specific areas touched, the rates of touches were higher to the body than to the floor, but the duration of contacts and the most touched areas were higher for the supporting surface than for the body. Until the age of 9 weeks, we found no consistent differences in the rate of touch between head and trunk. Infants also did not display significant differences in their rate of touch between right and left hand or between conditions. However, we discovered that in the earlier weeks, infants engaged more often in what we called “complex touches”. Complex touches were touches performed across several body/floor areas in one continuous bout while the hand maintained contact with the body or floor. Single touches, in contrast, corresponded to one touch to one single body or floor area at a time. We suggest that infants are active explorers of their own body and peripersonal space from day 1 and that these early self-generated and deeply embodied sensorimotor experiences form the critical foundation from which future behaviors develop.

Service user and carer engagement is a foundational requirement of social work education. Despite this, questions remain about how diverse experiences are represented and who might be excluded from involvement. This paper focusses on one group of people who it is suggested are excluded from involvement, people with profound and multiple learning disabilities. Evidence is presented which demonstrates the extent to which this group have been marginalised and excluded from processes of involvement. The paper then provides a case study of one universities’ experience of developing work in this area, when a man with profound and multiple learning disabilities was commissioned to design and deliver specialist teaching for a group of qualifying social work students. We argue that the main barrier to inclusive involvement for people with profound and multiple learning disabilities is the attitudes and assumption of others about what they are capable of. We demonstrate how involvement in social work educat...

This paper presents a controller integrity monitoring method for a class of second-order nonlinear uncertain systems incorporating neural network-based adaptive control algorithms. The adaptive neural network model is employed to ensure robust tracking performance in the presence of certain modeling uncertainty under consideration during the offline controller design process. Based on Lyapunov stability analysis, an online controller integrity monitoring scheme is developed to detect the occurrence of controller software/algorithm faults and unanticipated physical component faults, which may lead to unstable learning behaviors and malfunctions of the adaptive controller. Adaptive thresholds for detecting controller malfunctions are derived, ensuring the robustness with respect to modeling uncertainty and neural network approximation error. Additionally, the detectability conditions are investigated, characterizing the class of detectable software faults and unanticipated physical faults. An upper bound on the fault detection time is also established. Simulation results are shown to illustrate the effectiveness of the proposed method.

The generation of novel chemical leads for clinical development is a constant challenge in the pharmaceutical industry. The synthesis of DNA-encoded libraries has emerged as a powerful method for hit and lead generation. We report the development of the tertiary amino effect reaction on DNA-tethered substrates. A variety of ortho-dialkylaminoaryl aldehydes undergo a cascade reaction involving a Knoevenagel condensation, a [1,5]-hydride shift, and a Mannich cyclization to give diversely substituted spirocycles. NMR analysis of substrates bearing an enriched double-13C label confirmed product formation. The net formation of two carbon–carbon bonds adds to the few examples of carbon–carbon forming reactions performed in presence of DNA-encoding systems.

PS B, a naturally occurring CD4(+) T-cell simulating zwitterionic polysaccharide from Bacteroides fragilis ATCC 25285/NCTC 9343, was conjugated with aminooxy Thomsen Friedenreich (TF or T) [α-d-Gal-(1,3)-β-d-GalNAc-ONH2] tumor antigen. Immunization in Jax C57BL/6, followed by ELISA revealed IgM and IgG antibody TF specificity. FACS data noted preferential binding to TF-laced MCF-7 cells but not to HCT-116 cells.

Potassium sodium niobate (KNN) is a leading candidate for certain applications within the ongoing move towards lead-free ferroelectric and piezoelectric materials. One common synthetic route for synthesizing KNN utilizes sol-gel chemistry, which typically suffers from issues with low film quality (due to bulky leaving groups), air sensitivity, and hazardous waste. Here we describe a green synthetic pathway to KNN thin films using polyoxometalate precursors in the form of X8Nb6O19 (X=Na, K, H) salts. These hexaniobate clusters are soluble in water and stable in air, allowing for simple deposition with a benign precursor. The alkali content is tunable based on control of pH and subsequent protonation of the hexaniobate cluster. The aqueous precursor solutions create dense polycrystalline KNN films on polycrystalline sapphire substrates. In addition, high quality KNN thin films are observed to grow epitaxially on (001) SrTiO3 substrates. Overall, this synthetic approach demonstrates a flexible pathway to Nb-based thin films with an emphasis on the sustainable chemical practices that are at the heart of modern chemistry and the quest for lead-free ferroelectrics.

Objective: To describe the chief complaints of people older than 65 years who seek chiropractic care at a chiropractic teaching clinic and assess the case mix available at the clinic. Methods: One hundred patient files were included in this study. Patient files were included if the patient was older than 65 years when he or she initiated care at the teaching clinic. Data on age, sex, and chief complaints were recorded. Results: Of the patients included in this study, 55% were female. The mean age of patients was 69.5 years, with an age range of 65–88 years. The most common chief complaint was low back pain, with 45% of patients reporting this as their chief complaint. The second most prevalent complaint was neck pain, followed by patients seeking care with no presenting complaints (14%) and patients with extremity complaints (8%). Groin pain, hip pain, balance problems, headaches, and visceral complaints were also reported. Conclusion: The most common reasons that older patients presented for chiropractic care were for back and neck pain. The case mix was considered similar to practices in the country.

In this chapter, we discuss how perception and action are intimately linked to the processes of exploration and selection. Exploration, which we define as trying several variations of the behavior, and selection, which involves attempting to reproduce the behaviors that work, are essential for learning about the environment, discovering the properties of objects, and for acquiring skills in relation to goals. Exploration and selection happen in the moment and over time as behaviors are repeated, hence leading to their fine-tuning to the goal. We illustrate this time-dependent developmental process using several examples from infants reaching for objects, to discovering object properties, to learning about the functionality of tool use, and even to word learning. As we present those examples, we introduce a more detailed perception-action loop to illustrate those moment-to-moment behaviors and show how they contribute to the acquisition of perceptual, motor, and cognitive skills in infancy.

We present our work on integration of quantifier elimination (QE) technique with model checking and compositional verification. We begin by showing how quantifier elimination problems arise in these applications. In a k-induction based model checking approach, the verification problems of the base and inductive steps can be reduced to the QE problems in which all the variables are existentially quantified. It follows that a k-induction based model checker can be extended with QE tools to provide back-end solver options. Our implementation of integrating the QE tool Redlog with the model-checker JKind showed the successful resolution of a non-linear computation (emanating from a fuzzy logic operation) that the SMT-solver supported JKind was unable to resolve. Thus the QE tool provides a parallel option to the model-checker. The integrations of the QE tool Redlog with the model-checker JKind has been completed by us, and relies on writing the SMT-to-Redlog translator. On the other hand, in compositional verification, the goal is to prove a system level assume-guarantee style contract from the given component level contracts. The existing compositional verification tool AGREE tries to sequentially prove that each component’s assumption is satisfied by the system assumption and other components’ guarantees, following which the conjunction of all component contracts and system assumption is used to verify the system guarantee. In contrast, we propose a QE-based approach to derive, in a single step, the strongest system contract, from which any postulated system contract can be verified by performing a simple implication verification from the former to the later. We show how the compositional reasoner AGREE can be strengthened through its integration with the QE tool Redlog. We implemented our above approaches in a new prototype tool called ReLIC (Reduced Logic Inference for Composition) and demonstrated it through an illustrative example.

Resting membrane potential (RMP) and intracellular Ca2+ concentration [(Ca2+)i] are involved in tumorigenesis and metastasis. The present study investigated whether functional cardiac Na+ channels are expressed in human melanoma cells (WM 266-4) and its nonmalignant human melanocytes (HMC), as well as whether they participate in RMP maintenance and Ca2+ homeostasis. Confocal microscopy and western blot analysis were used to detect Na+ channels. The patch-clamp technique was employed to record Na+ currents and action potentials. Cytoplasmic Ca2+ was measured by loading Fluo-4. Cardiac (Nav1.5) Na+ channels were expressed in HMCs and WM 266-4 cells. Tetrodotoxin (TTX) dose-dependently blocked Na+ currents in WM 266-4 while HMCs had no Na+ currents. Ultraviolet light induced similar action potentials in HMCs and WM 266-4 cells, which were abolished by transient receptor potential A1 channel-specific blocker, HC-030031. Compared with HMCs, RMP was substantially depolarized in WM 266-4. TTX hyperpolarized RMP in WM 266-4 cells at a concentration of 30 µM, which facilitated Ca2+ influx. Compared with HMCs, (Ca2+)i was significantly higher in WM 266-4 cells and was elevated by 30 µM TTX. Collectively, Cardiac Na+ channels depolarize RMP and inhibit Ca2+ uptake in melanoma cells possibly contributing to tumorigenesis and metastasis. Na+ channel agonists may be developed to treat melanoma such as WM 266-4.

Our previous studies have demonstrated that ultraviolet radiation-induced skin photo-aging is associated with collagen degradation, dehydration, and inflammation. While the cellular and molecular m...

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care.METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366.FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

Motivated by growing demand for radio frequency spectrum, spectrum regulators are laying the groundwork for centralized, dynamic spectrum sharing systems that will enable efficient access to spectrum for new wireless technologies. With a database of spectrum user information, and an infrastructure of spectrum sensors, these sharing systems will leverage cognitive radio concepts to automatically identify suitable spectrum for users. Whether incumbent users should provide information directly to the database or rely on the sensor network for detection remains an open question with implications for the effectiveness of the sharing and the privacy of the users. Both methods present the potential to explore a privacy-performance tradeoff within the sharing system. In this work we assess this tradeoff with both sensing and interface obfuscation approaches in a spectrum sharing system. We identify key design parameters in a formal model for the sharing system architecture, and conduct a thorough simulation study of a real-world use case to quantify privacy and performance. While abstract models suggest sensing based solutions should compare favorably with obfuscation heuristics applied to the user interface, the performance of realistic sensor network designs suggests that achieving a favorable privacy-performance tradeoff with sensor networks may be significantly limited by practical considerations.

In this chapter, we discuss how perception and action are intimately linked to the processes of exploration and selection. Exploration, which we define as trying several variations of the behavior, and selection, which involves attempting to reproduce the behaviors that work, are essential for learning about the environment, discovering the properties of objects, and for acquiring skills in relation to goals. Exploration and selection happen in the moment and over time as behaviors are repeated, hence leading to their fine-tuning to the goal. We illustrate this time-dependent developmental process using several examples from infants reaching for objects, to discovering object properties, to learning about the functionality of tool use, and even to word learning. As we present those examples, we introduce a more detailed perception-action loop to illustrate those moment-to-moment behaviors and show how they contribute to the acquisition of perceptual, motor, and cognitive skills in infancy.

Airworthiness certification of military aircraft is accomplished by the developing military service. Air Force programs use the qualitative criteria outlined in MIL-HDBK-516B, “ASC/ EN Airworthiness Certification Criteria Expanded Version of MIL-HDBK-516B” (September 26, 2005) to aid the development of program-specific airworthiness criteria. The generalized criteria in this document are used to construct the specific criterion and associated artifacts — evidence of compliance — as the basis for making an airworthiness determination. This paper describes the process of transitioning from qualitative to specific criteria, and then examines the applicability of the existing guidance in MIL-HDBK-516B to autonomous decision-making adaptive air vehicle systems. Recommendations are made for future research and criteria expansion. An integrated approach that uses the most promising emerging and existing design, analysis, and validation and verification techniques is proposed as a means to develop the artifacts for certification coverage of autonomous adaptive unmanned air vehicle systems.

Display Omitted The predictive value of animal safety studies for humans is studied.The statistical impact of specific adverse events for drug withdrawal is studied.Specific animal adverse events which impact human safety are identified.A model for predicting risk of withdrawal or drug failure due to safety is reported. This study examines the ability of nonclinical adverse event observations to predict human clinical adverse events observed in drug development programs. In addition it examines the relationship between nonclinical and clinical adverse event observations to drug withdrawal and proposes a model to predict drug withdrawal based on these observations. These analyses provide risk assessments useful for both planning patient safety programs, as well as a statistical framework for assessing the future success of drug programs based on nonclinical and clinical observations.Bayesian analyses were undertaken to investigate the connection between nonclinical adverse event observations and observations of that same event in clinical trial for a large set of approved drugs. We employed the same statistical methods used to evaluate the efficacy of diagnostic tests to evaluate the ability of nonclinical studies to predict adverse events in clinical studies, and adverse events in both to predict drug withdrawal. We find that some nonclinical observations suggest higher risk for observing the same adverse event in clinical studies, particularly arrhythmias, QT prolongation, and abnormal hepatic function. However the lack of these events in nonclinical studies is found to not be a good predictor of safety in humans. Some nonclinical and clinical observations appear to be associated with high risk of drug withdrawal from market, especially arrhythmia and hepatic necrosis. We use the method to estimate the overall risk of drug withdrawal from market using the product of the risks from each nonclinical and clinical observation to create a risk profile.

Carsharing organizations (known as car clubs in Britain) are today evolving in new ways. One noteworthy development is the growth of the business-to-business (B2B) market, which is motivated in part by operators’ desire to smooth the temporal profile of overall carsharing demand and thereby increase aggregate fleet-utilization rates. In contrast to the widely-studied business-to-consumer (B2C) market, however, comparatively little is known about the B2B segment. This study fills this gap by drawing on a national survey of both Britain’s B2B carsharing members (n = 682) and employers’ corporate travel administrators that oversee an organization’s B2B carsharing membership (n = 127). Analytical methods included both descriptive statistics and multivariate regression techniques. We find that two-thirds (68 %) of B2B members use carsharing for their usual business travel, and that half (51 %) of them previously used their own car for such travel. Approximately one in seven (15 %) respondents indicated that their carsharing membership through their employer has changed their travel habits by allowing them to commute to work less often by private car, as they do not require their own personal car for work-related travel during their workday. It appears that car use for (non-commuting) business purposes may increase, however. This paper concludes with a discussion of open questions that are suggested to motivate the future research agenda.

Aging population has been growing as life expectancy increases. In the years to come a much larger percentage of the population will be dependent on others for their daily care. According to a recent report more than 11 million seniors live alone in the USA. These seniors may face serious consequences when they have an emergency situation. However health-monitoring systems are often not affordable for many seniors. The remote health monitoring system presented in this paper addresses the challenge to provide caregivers an emergency alert system for the elderly based on monitoring of their heart rates, breathing activities, and room temperature measurements. The device also allows the dependents to make on demand request for assistance. The remote communication is enabled through the cellular telephone services; so there is no special or additional subscription services needed. This is essential to make the device more affordable for the elderly. We expect that this affordable remote health-monitoring system can be used to help seniors who live alone be safer and healthier.

Intelligent transportation systems (ITS) have been deployed worldwide as a cost-effective means to mitigate concerns about congestion, safety, environment, and other issues. Researchers commonly use questionnaire surveys to gauge the public's response to the success of ITS deployments in achieving the stated ITS goal of improving customer satisfaction as well as the other goals of strengthening transportation safety, mobility, efficiency, productivity, energy, and environmental efforts. To differentiate itself from previous research, this study sought to identify how Michigan travelers who actively sought travel information perceived benefits from advanced traveler information systems (ATIS). Toward this objective, a revealed preference questionnaire survey was developed and linked on the Michigan Department of Transportation's foremost online hub for publicly available travel information, Mi Drive. The survey included questions about the typical sources of travel information, frequency of information use, tendency to alter predeparture travel behaviors as a result of information, and similar topics. The study used ordered logistic regression modeling to uncover some key findings, which included the influence of time of year, resident location, and travel information affinity on active ATIS users' perception of ATIS. Discovery of such relationships could enable transportation agencies to enhance the marketing and operation of ATIS services such as Mi Drive and thus strengthen the systemwide benefits experienced by motorists.

This paper introduces a technique using a laser rangefinder sensor mounted on a movable gimbal system that enables an unmanned aerial vehicle (UAV) to maintain a specific height above changing terrain. The system and controller design are explained, and the performance of the laser rangefinder is compared with ultrasonic and GPS-based measurements.

As the demand for mobile data traffic continues to increase, regulatory bodies have proposed to allow radar and communication systems to co-exist in the same frequency band. The success of co-existence would depend on how well the interference which one system exerts to the other can be controlled. Recently proposed co-existence approaches use a precoder at the communication and/or radar system, with the precoding matrices optimally designed to control the interference to the radar. However, this could potentially pose a security risk for the radar, as the precoding matrix assigned to the communication system contains implicit information about the radar. This paper is a first step towards understanding whether the signaling scheme of a smartphone co-existing with a radar could be used by an adversary to infer radar information, for example, the radar location. Different precoder matrices are considered, and the likelihood of the adversary estimating the angle at which the radar is located is computed based solely on the observed precoder. We simulate an adversary inference attack and show that such a breach to the radar's privacy does pose a reasonable risk.

Background Studying the role of gastroenterologists' attire can provide insight into patients' perceptions and help us optimize the physician-patient relationship. In this study we assessed patients' preference concerning gastroenterologists' attire, and its influence on patients' trust, empathy and perceptions of the quality of care in the clinic and endoscopic suite. Methods A cross-sectional survey was conducted from August 2016 to February 2017. A total of 240 consecutive patients who presented to the Gastroenterology Department at the University of Florida in Jacksonville both in the clinic and endoscopic suite were included in this study. The questionnaire applied included 8 questions concerning patients' preferences regarding gastroenterologists' attire and the impact the attire had on patients' trust, empathy and perceptions of quality of care. Results Overall, 85% of patients preferred scrubs to formal dress clothes. The preference for scrubs was higher in the endoscopic suites (89% and 93%) compared to the outpatient office (66%, P

As of late, hierarchical Fuzzy Inference Systems (hFIS) have received considerable attention because of their ability to control complex decision-making procedures. Although the performance of hFISs appears to be extremely effective in complex scenarios, there is a question about the differences between the hierarchical and single FISs (sFIS) and the relationship between the two. In this work, a transformation is derived which converts a Mamdani type hFIS into its equivalent sFIS representation. This is accomplished by equating their output membership functions. The equivalency between the outputs of the two representations is proven using a Satisfiability Modulo Theories (SMT) solver approach. Furthermore, we provide a detailed development procedure and results are presented which demonstrate the ease of implementation of the transformation as well as a wide applicability to meaningful large-scale problems.

The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene.

In response to increasing demand on the radio frequency spectrum, regulators are implementing new spectrum access systems to share spectrum among diverse users. These systems leverage cognitive radio concepts to automatically identify suitable spectrum for users, avoiding harmful interference with higher priority users. An infrastructure of spectrum sensors is a key component of the spectrum access system, providing the means for the system to identify necessary protections. The geolocation precision of the sensing system will be limited in practice due to privacy concerns of the priority users as well as cost limitations. In this work, we examine the design options for the sensing component of a spectrum access system in terms of user performance and privacy. We apply machine learning techniques to treat the problem of estimating the priority users' state from sensor measurements, finding that the geolocation precision is closely tied to the density of the sensor deployment, and that the secondary user performance degrades rapidly if the density is too low, highlighting a tradeoff between priority user privacy and secondary user performance.

While many widely accepted methods and techniques exist for validation and verification of traditional controllers, at this time no solutions have been accepted for Fuzzy Logic Controllers (FLCs). Due to the highly nonlinear nature of such systems, and the fact that developing a valid FLC does not require a mathematical model of the system, it is quite difficult to use conventional techniques to prove controller stability. Since safety-critical systems must be tested and verified to work as expected for all possible circumstances, the fact that FLC controllers cannot be tested to achieve such requirements poses limitations on the applications for such technology. Therefore, alternative methods for verification and validation of FLCs needs to be explored. In this study, a novel approach using formal verification methods to ensure the stability of a FLC is proposed. Main research challenges include specification of requirements for a complex system, conversion of a traditional FLC to a piecewise polynomial representation, and using a formal verification tool in a nonlinear solution space. Using the proposed architecture, the Fuzzy Logic Controller was found to always generate negative feedback, but inconclusive for Lyapunov stability.

Cytochrome P450 46A1 (CYP46A1) is a brain-specific cholesterol 24-hydroxylase responsible for the majority of cholesterol elimination from the brain. Genetically increased CYP46A1 expression in mice leads to improved cognition and decreases manifestations of Alzheimer disease. We found that four pharmaceuticals (efavirenz (EFV), acetaminophen, mirtazapine, and galantamine) prescribed for indications unrelated to cholesterol maintenance increased CYP46A1 activity in vitro. We then evaluated the anti-HIV medication EFV for the mode of interaction with CYP46A1 and the effect on mice. We propose a model for CYP46A1 activation by EFV and show that EFV enhanced CYP46A1 activity and cerebral cholesterol turnover in animals with no effect on the levels of brain cholesterol. The doses of EFV administered to mice and required for the stimulation of their cerebral cholesterol turnover are a hundred times lower than those prescribed to HIV patients. At such small doses, EFV may be devoid of adverse effects elicited by high drug concentrations. CYP46A1 could be a novel therapeutic target and a tool to further investigate the physiological and medical significance of cerebral cholesterol turnover.

Loneliness is the subjective sense of social isolation (Cacioppo & Patrick, 2008). Chapter 1 argues that loneliness is puzzling because of the evidence that people form connections easily and break connections reluctantly (Baumeister & Leary, 1995). In Chapter 1, I argue that loneliness may result from lower familiarity with others and higher residential mobility of modern society. This explanation is challenged by the social pain model. This model argues loneliness evolved to motivate connection when belonging is inadequate (Cacioppo & Patrick, 2008). Loneliness should motivate lonely people to connect with others, and thus override the effects of lower familiarity and greater residential mobility. Therefore, either loneliness is insufficient at motivating lonely people to form connections, or lonely people lack the ability to form connections despite motivation. This thesis examined the overriding research question of whether lonely people pursue belonging, and if so, whether this pursuit is successful. This thesis examined the pursuit of belonging by examining sociability. In Chapter 2, I analysed historical trends of sociability, social networks, and loneliness. I reviewed evidence that sociability has shown large decreases in recent decades. People are less likely to attend church, join unions, or join clubs (Putnam, 2000). I assessed whether this decline in sociability is associated with increases in loneliness. In Study 1, I examined trends in loneliness among college students, and found that over recent decades loneliness has decreased. In Study 2, I examined data from a representative survey of high school students and found that over recent decades loneliness decreased, whereas social networks became poorer. Chapter 2 suggests sociability is not a major determinate of loneliness, but only provides indirect evidence of this link. In Chapter 3, I directly assessed the link between sociability and loneliness. I used a cross-sectional design to test the association between sociability and loneliness. I found that lonely people were less sociable and this was independent of other predictors of loneliness including communal orientation, acceptance, and reinforcement sensitivity. Chapter 3 had two main limitations. First, chapter 3 was cross-sectional. Second, the sociability measure used appears to assess enjoyment around others, whereas sociability may encompass tendency and effort to engage with others, which may be distinct from enjoyment. In Chapter 4, I addressed these limitations by conducting a longitudinal study, and used a measure that assessed multiple aspects of sociability. I used an exploratory factor analysis on the existing sociability scale plus novel items and found five additional factors of sociability: desire for belonging, tendency to engage with strong ties, effort networking,effort with strong ties, and tendency to engage with weak ties. I measured sociability and loneliness at two time points seven weeks apart. Two cross-lagged relationships were found that supported the social pain model. First, collective disconnection—the type of loneliness associated with group ties—led to more social enjoyment. Second, isolation—the subjective feeling of loneliness—led to greater desire for belonging. The social pain model contrasts with the social desensitization model, which argues that lonely people become desensitized to belonging and therefore predicts that loneliness will lead to less sociability (Moller, Deci, & Elliot, 2010). I found one cross-lagged relationship that supported the social desensitization model. Relational disconnection—the type of loneliness associated with interpersonal ties—led to less social desire. I found some evidence that sociability reduces loneliness. The tendency to engage with strong ties reduced isolation. Low levels of shyness reduced feelings of isolation. In contrast, one form of sociability actually increased loneliness. The tendency to engage with strong ties led to more relational disconnection. The previous three chapters looked at pursuing belonging through sociability. In Chapter 5, I argued that people derive a sense of belonging by being valuable to others, and that people may become valuable to others through work. In Chapter 5, I presented the findings of a longitudinal study measuring work engagement and loneliness at two time points, three months apart. There was no clear evidence that belonging affected work engagement or that that work engagement reduced loneliness over time. The thesis concludes in Chapter 6 summarising the evidence supporting both the social pain and social desensitization models for sociability. Loneliness appeared to increase and decrease people’s effort to connect with others, depending on the context. I did not find support for work satisfying belonging or for belonging affecting work engagement. I found sociability could reduce loneliness, but it could also increase loneliness. Thus, loneliness can increase and decrease the motivation to pursue belonging, but the motivation to pursue belonging does not strongly affect loneliness.

A rare phenomenon, the extraoral traumatic penetration of a foreign body into the lumen of the parotid duct, is described. The ensuing obstructive symptomatology and its diagnostic approach and therapy are reviewed.

Patient: Female, 24 Final Diagnosis: Pinworms infection Symptoms: Abdominal pain • bloating Medication: — Clinical Procedure: Colonoscopy and biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Inflammatory bowel disease (IBD) is well recognized in developed countries and is generally among the differential diagnoses of young patients presenting with refractory diarrhea once other more common etiologies have been excluded. Pinworm infections, on the other hand, are not as common among adults in the United States. Case Report: Based on computed tomography features, a 24-year-old female patient with a history of multiple autoimmune disorders presented with abdominal pain and was diagnosed recently with Crohn’s disease. Colonoscopy was significant for pinworms seen throughout the colon. Colonic biopsy was negative for inflammatory bowel disease (IBD)-related changes. Conclusions: The diagnosis of IBD is a serious label that requires biopsy confirmation before committing to possibly lifelong treatment and possible adverse effects. Even in the most typical patient and when the presentation and imaging are classical, uncommon conditions (like Enterobius infection in this case) may preclude appropriate diagnosis and management.