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Discrepancies between automatically activated associations (i.e., implicit evaluations) and explicit evaluations of motives (measured with a questionnaire) could lead to greater information processing to resolve discrepancies or self-regulatory failures that may affect behavior. This research examined the relationship of health and appearance exercise-related explicit-implicit evaluative discrepancies, the interaction between implicit and explicit evaluations, and the combined value of explicit and implicit evaluations (i.e., the summed scores) to dropout from a yearlong exercise program. Participants (N = 253) completed implicit health and appearance measures and explicit health and appearance motives at baseline, prior to starting the exercise program. The sum of implicit and explicit appearance measures was positively related to weeks in the program, and discrepancy between the implicit and explicit health measures was negatively related to length of time in the program. Implicit exercise evaluations and their relationships to oft-cited motives such as appearance and health may inform exercise dropout.

Fructose consumption is a risk factor for metabolic disease. We recently demonstrated that fibroblast growth factor 21 (FGF21), a metabolic hormone involved in lipid and glucose metabolism, is acutely stimulated in humans by 75 g oral fructose, with peak levels occurring 2 h after consumption. This study reports on the dose dependency and reproducibility of the FGF21 response to fructose.Lean, healthy adults drank either five different doses of fructose dissolved in water, each separated by 2 weeks, or the same dose on three occasions, each separated by 1 week.Fibroblast growth factor 21 levels peaked at 2 h in a dose-dependent manner. No significant increase in FGF21 was seen after consumption of 10 g fructose, while robust increases were seen after drinking solutions containing 30, 50 and 75 g. At 2 h, the minimal fold change of FGF21 was highest following a 75 g fructose drink, and all subjects demonstrated at least a doubling of FGF21 levels following consumption of this dose.The increase in FGF21 following an oral fructose challenge is dose dependent, with levels peaking at 2 h independent of dose. The FGF21 response to 75 g fructose is also highly reproducible within individuals.By demonstrating that the FGF21 response to fructose is dose dependent and reproducible, this study deepens current understanding of FGF21 fructose dynamics and physiology in humans. This is an important area of clinical interest given associations between fructose intake and a wide variety of metabolic derangements.

Introduction: The Framingham Studies revealed that diabetes mellitus (DM) predisposed subjects to a two- to eight-fold increase in the risk of developing heart failure (HF). However, there is much less information available about the reverse issue; namely, whether there is an increased risk of developing DM in patients with HF. We sought to determine if reversal or partial reversal of HF through aortic valve replacement (AVR) would improve glycemic control in patients with DM at our institution. Methods: The electronic medical records of 57 consecutive diabetic patients were retrospectively analyzed. These patients had undergone AVR at a medium-sized academic medical center from May 2005 through May 2015, and had glycated hemoglobin (HbA1C) measured before and after the procedure. The variables of interest included HbA1C, and echocardiographic parameters such as left ventricular ejection fraction (LVEF), tricuspid regurgitation velocity (TRV), and right ventricular systolic pressure (RVSP) before and after valve replacement. Results: HbA1C decreased significantly during the first year after replacement, from 7.1% (range 4.4 - 13.0%) before surgery to 6.5% in the first year (P < .05). In addition, the calculated RVSP decreased from 44 mmHg (20 - 79 mmHg) to 37 mmHg (P < .05 from the preoperative value). LVEF and TRV did not change significantly. Reductions in HbA1C and RVSP during the first year were greater in patients who experienced an increase of 5% or more in EF at their first postoperative measurement. Patients with higher baseline HbA1C values had a greater decline in glycated Hb during the first year (P < .01). Conclusion: AVR was associated with a reduction of HbA1C and a decrease in pulmonary artery systolic pressure within one year of the procedure.

Objectives The objectives of this study were to (i) investigate directional influences of self-efficacy, outcome satisfaction, and attendance during an exercise programme and (ii) examine the predictive capabilities of self-efficacy and outcome satisfaction on participant dropout. Methods Adults aged 35-65 years were recruited to a 12-month exercise programme. Self-efficacy was collected at baseline, three, six, nine, and 12 months, and outcome satisfaction at the same time-points except baseline. Cross-lagged panel analyses and logistic regression analyses were conducted to examine the primary and secondary objectives, respectively. Results Coping and scheduling self-efficacy had stronger reciprocal relationships with outcome satisfaction than task self-efficacy, although the strength of these relationships varied across time. Initially, task self-efficacy predicted programme attendance. Midway through the programme, outcome satisfaction predicted attendance, and by the end of the programme, coping self-efficacy was the strongest predictor of attendance. Self-efficacy and outcome satisfaction did not predict programme dropout. Conclusions The results support the reciprocal relationship between outcome satisfaction and scheduling and coping self-efficacy and highlight the importance of sequentially targeting different beliefs and skills to facilitate successful initiation and maintenance of exercise behaviour. Statement of contribution What is already known on this subject? Self-efficacy and outcome satisfaction are related to exercise behaviour. The relationship between self-efficacy and outcome satisfaction are typically considered unidirectional. The longitudinal relationships among self-efficacy, outcome satisfaction, and physical activity participation are unclear. What does this study add? Outcome satisfaction had reciprocal relationships with both coping and scheduling self-efficacy for exercise. The importance of self-efficacy and outcome satisfaction to exercise attendance changes over time. Task self-efficacy was the strongest predictor of initial programme attendance. Midway through the programme, outcome satisfaction and task self-efficacy were the strongest predictors of attendance, and by the end of the programme, coping self-efficacy was the strongest predictor.

Replacement of dead neurons following ischemia, either via enhanced endogenous neurogenesis or stem cell therapy, has long been sought. Unfortunately, while various therapies that enhance neurogenesis or stem cell therapies have proven beneficial in animal models, they have all uniformly failed to truly replace dead neurons in the ischemic core to facilitate long-term recovery. Remarkably, we observe robust repopulation of medium-spiny neurons within the ischemic core of juvenile mice following experimental stroke. Despite extensive neuronal cell death in the injured striatum of both juveniles and adults at acute time points after ischemia (24 h and 7 d), mature newborn neurons replaced lost striatal neurons at 30 d post-ischemia. This neuronal repopulation was found only in juveniles, not adults, and importantly, was accompanied by enhanced post-ischemic behavioral recovery at 30 d. Ablation of neurogenesis using irradiation prevented neuronal replacement and functional recovery in MCAo-injured juvenile mice. In contrast, findings in adults were consistent with previous reports, that newborn neurons failed to mature and died, offering little therapeutic potential. These data provide support for neuronal replacement and consequent functional recovery following ischemic stroke and new targets in the development of novel therapies to treat stroke.

Global ischemia in childhood often leads to poor neurologic outcomes, including learning and memory deficits. Using our novel model of childhood cardiac arrest/cardiopulmonary resuscitation (CA/CPR), we investigate the mechanism of ischemia-induced cognitive deficits and recovery. Memory is impaired seven days after juvenile CA/CPR and completely recovers by 30 days. Consistent with this remarkable recovery not observed in adults, hippocampal long-term potentiation (LTP) is impaired 7–14 days after CA/CPR, recovering by 30 days. This recovery is not due to the replacement of dead neurons (neurogenesis), but rather correlates with brain-derived neurotrophic factor (BDNF) expression, implicating BDNF as the molecular mechanism underlying impairment and recovery. Importantly, delayed activation of TrkB receptor signaling reverses CA/CPR-induced LTP deficits and memory impairments. These data provide two new insights (1) endogenous recovery of memory and LTP through development may contribute to improved neurological outcome in children compared to adults and (2) BDNF-enhancing drugs speed recovery from pediatric cardiac arrest during the critical school ages.

INTRODUCTION Evaluation of von Willebrand factor (VWF) multimeric distribution is useful for subclassification of von Willebrand disease (VWD). Multimer analysis has historically been a manual, labor-intensive laboratory-developed test. The first commercial method for multimeric analysis was recently developed that utilizes a single instrument for gel electrophoresis, staining, and densitometry. The current study was undertaken to evaluate the performance characteristics of the new commercial method. METHODS Studies performed with the commercial method included evaluation of accuracy (method comparison), reference intervals (establishment of normal migration patterns in normal donor specimens), precision (multimer pattern reproducibility), and analytical sensitivity. RESULTS In the method comparison studies, concordant interpretations were obtained in 19 of 24 comparisons, including normal and abnormal specimens. The 5 specimens with discordant interpretations all involved slight differences and none were considered clinically significant. Thirty-eight normal donor specimens demonstrated normal multimer patterns. Multimer pattern reproducibility was demonstrated in normal and abnormal controls tested on each gel. In the sensitivity studies, adequate visualization of multimers was determined to require VWF protein concentrations of approximately 5%-10% of normal. CONCLUSION The commercial multimer method is a streamlined test that demonstrates comparable performance characteristics to our current laboratory-developed method and that provides the advantage of both electrophoresis gels and densitometry scans to aid interpretation.

Despite the importance of critical media work, much is to be learned about breast cancer representations within media discourses and the implications for women’s identity construction. Building on research from Australia from a discursive perspective, this article used an eclectic approach to critical discourse analysis to explore the cultural construction of breast cancer in 25 detailed stories within Canada’s two national newspapers, The Globe and Mail and the National Post. Ten images accompanying stories and 17 advertisements/public service announcements were also analyzed to contextualize discourses and subject positions/identities within the stories. Analysis of this media affords the unique opportunity to explore taken for granted assumptions and prevailing meanings about breast cancer and the implications for subjectivity. Two primary discourses were identified: a discourse of biomedicine and a discourse of healthism. Subject positions identified included “breast cancer survivor,” “the goo...

Background Intravascular catheter salvage may be attempted in clinically suitable cases in pediatric patients with catheter-related bloodstream infections. The purpose of this study was to assess the effectiveness of ethanol and hydrochloric acid (HCl) locks in achieving catheter salvage through decision-analysis modeling. Methods A Markov decision model was created to simulate catheter salvage using three management strategies: systemic antibiotics alone, antibiotics plus HCl lock, and antibiotics plus ethanol lock. One-way and two-way sensitivity analyses were performed for all model variables. Infection control rates and recurrence rates for each strategy were derived from prospective institutional data and existing pediatric literature. Costs were derived from institutional charges. Results With antibiotics alone, 73% of patients would require line replacement within 100days, compared to only 31% and 19% of patients treated with HCl and ethanol lock, respectively. Incremental cost per additional catheter salvaged is $89 for HCl lock and $456 for ethanol lock. Superior efficacy of adjunct lock therapy is insensitive to changes in the anticipated duration of central access requirement and to clinically relevant variations in all model input variables. Conclusion HCl or ethanol locks are cost-effective adjuncts to systemic antibiotics for attempted catheter salvage in the setting of catheter-related bloodstream infections.

Alternative organizations have become increasingly of interest in organizational theory. Previously understudied, these organizations have also been ignored or forgotten in the dominant narratives and spaces of commemoration. This further limits what we know about the past and the potential of alternative organizations. To illustrate this problem, we offer a specific case study of the forgotten alternative organizations and marginalized space of a former Finntown alongside the commemorative narratives and practices of capitalist entrepreneur heritage spaces. Extending organization theory on memory and forgetting, we detail how commemoration not only tends to legitimate capitalist forms of organizing, but also excludes alternatives. Finntowns, with their emphasis on cooperative organizations and community, provide a unique opportunity for organization studies to explore commemoration and forgetting in terms of power relations, time, and space. These marginalized spaces contained alternative organizations coexisting and contrasting with dominant capitalist organizations. Remembering their contributions means taking alternative organizations seriously, acknowledging their historic importance as well as their ability to be models for contemporary organizations.

Objective This study aims to describe how pharmacists utilise and perceive delegation in the community setting. Method Non-participant observations and semi-structured interviews with a convenience sample of community pharmacists working in Kent between July and October 2011. Content analysis was undertaken to determine key themes and the point of theme saturation informed sample size. Findings from observations were also compared against those from interviews. Key findings Observations and interviews were undertaken with 11 pharmacists. Observations showed that delegation occurred in four different forms: assumed, active, partial and reverse. It was also employed to varying extents within the different pharmacies. Interviews revealed mixed views on delegation. Some pharmacists presented positive attitudes towards delegation while others were concerned about maintaining accountability for delegated tasks, particularly in terms of accuracy checking of dispensed medication. Other pharmacists noted the ability to delegate was not a skill they found inherently easy. Comparison of observation and interview data highlighted discrepancies between tasks pharmacists perceived they delegated and what they actually delegated. Conclusions Effective delegation can potentially promote better management of workload to provide pharmacists with additional time to spend on cognitive pharmaceutical services. To do this, pharmacists' reluctance to delegate must be addressed. Lack of insight into own practice might be helped by self-reflection and feedback from staff. Also, a greater understanding of legal accountability in the context of delegation needs to be achieved. Finally, delegation is not just dependent on pharmacists, but also on support staff; ensuring staff are empowered and equipped to take on delegated roles is essential.

Locally-commissioned pharmacy public health services have developed in England over the last 20 years. Few studies have sought pharmacist views on commissioning and provision of public health services in general. This study sought views of community pharmacists (n = 778) in 16 areas of England on services provided, decisions about services, support, promotion and future developments, using a postal questionnaire with two reminders. Response rate was 26.5% (206). Funded public health services provided most frequently were: emergency contraception (71%), smoking cessation (62%), and supervised drug consumption (58%). Blood pressure monitoring was provided by 61% and was considered to be one of the services pharmacists perceived as being most valued by customers, but was not National Health Services (NHS)-funded. Motivation for providing public health services was professional not financial, particularly from those working in independent pharmacies. Only 35% were personally involved in deciding which services to deliver, and fewer than 20% based decisions on local public health reports. Pharmacists had positive attitudes towards providing public health services, but mixed views on support for services and their promotion. Most thought services would increase in future, but were concerned about commissioning. Both national and local support is needed to ensure future commissioning of pharmacy public health services.

Objectives The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). Methods A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. Results A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05–1.5%). Conclusions Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.

Background There is growing evidence around interruptions, multi-tasking and task-switching in the community pharmacy setting. There is also evidence to suggest some of these practices may be associated with dispensing errors. Up to date, qualitative research on this subject is limited. Objective To explore interruptions, multi-tasking and task-switching in the community setting; utilising an ethnographic approach to provide a detailed description of the circumstances surrounding such practices.Setting Community pharmacies in England, July–October 2011. Method An ethnographic approach was taken. Non participant, unstructured observations were utilised to make records of pharmacists’ every activity. Case studies were formed by combining field notes with detailed information on pharmacists and their respective pharmacy businesses. Content analysis was undertaken both manually and electronically, using NVivo 10. Main outcome measure To determine the factors influencing interruptions, multitasking and task-switching in the community pharmacy setting. Results Response rate was 12 % (n = 11). Over fifteen days, a total of 123 h and 58 min of observations were recorded in 11 separate pharmacies of 11 individual pharmacists. The sample was evenly split by gender (female n = 6; male n = 5) and pharmacy ownership (independent n = 5; multiple n = 6). Employment statuses included employee pharmacists (n = 6), owners (n = 4) and a locum (n = 1). Average period of registration as a pharmacist was 19 years (range 5–39 years). Average prescription busyness of pharmacies ranged from 2600 to 24,000 items dispensed per month. All observed pharmacists’ work was dominated by interruptions, task-switches, distractions and multi-tasking, often to manage a barrage of conflicting demands. These practices were observed to be part of a deep-rooted culture in the community setting. In particular, support staff regularly contributed to interruptions and distractions for pharmacists; pharmacists in turn continued to permit these. Novel directional work maps illustrated the extent and direction of task-switching and multi-tasking employed by pharmacists. Conclusions In this study pharmacists’ working practices were permeated by interruptions, distractions and multi-tasking. Task-switching was also frequently employed by pharmacists. Changes to working practices by both pharmacists and support staff would help to minimise these which in turn has the potential to lead to safer and more efficient methods of working.

Wearable sensor technology continues to advance and provide significant opportunities for improving personalized healthcare. In recent years, advances in flexible electronics, smart materials, and low-power computing and networking have reduced barriers to technology accessibility, integration, and cost, unleashing the potential for ubiquitous monitoring. This paper discusses recent advances in wearable sensors and systems that monitor movement, physiology, and environment, with a focus on applications for Parkinson’s disease, stroke, and head and neck injuries.

The imbalance resulting from an increasing number of medical school graduates combined with a relatively stable number of residency spots is creating a challenge for U.S. medical students attempting to secure postgraduate residency training. This trend increases the stakes for medical students in their applications to residency training programs and places much higher importance on performing effectively during residency interviews. With little to no formal training in interviewing skills, U.S. medical school graduates may be ill prepared to face challenges presented during both formal and informal residency interviews. In order to better prepare fourth-year medical students at the Vanderbilt University School of Medicine, faculty mentors constructed and implemented a comprehensive residency interview practice performance initiative entitled “Mock Interviews”. The mentors enlisted available faculty from within the learning communities to conduct these interviews and provide immediate feedback to students in advance of their actual residency interviews. Collected data show that this program has been progressively well received and quite successful in helping students achieve an increased level of perceived preparedness in their residency interviews. Requiring minimal cost and little infrastructure, and utilizing available resources within most medical schools, this program appears to serve as a logical next step in the training of medical students for securing postgraduate residency spots.

The purpose of this study was to evaluate the usefulness of chest radiography in the direction of postbronchoscopy clinical therapy. From 2001 to 2011, 368 rigid bronchoscopies were performed at a single institution in 221 children. Indications for bronchoscopy, concomitant bronchoscopic procedures, and results of postoperative chest radiography were evaluated. Rigid bronchoscopy was performed in children at a median age of 2.21 years (range, two days to 20 years). Chest radiography was performed at the discretion of the primary surgeon after 275 (74.7%) procedures. Malpositioning of the endotracheal or tracheostomy tube occurred in 1.5 per cent (n = three of 203) of ventilated patients postbronchoscopy. Pneumothorax occurred in 0.5 per cent (n = two of 368) of children and followed laser degranulation (n = one of 117 [0.9%]) and removal of an aspirated foreign body (n = one of 80 [1.3%]). Neither child required tube thoracostomy. Three children necessitated intraoperative tube thoracostomy placement for symptomatic pneumothoraces before radiographic assessment. No children sustained postprocedural complications in the absence of postbronchoscopy radiography. Postbronchoscopy chest radiography in the absence of defined symptomatology is not associated with a change in the postprocedural treatment course, suggesting selective application may be appropriate after at-risk bronchoscopic interventions. Such practice will limit the future cost and radiation exposure associated with this common procedure.

This study examined the extent to which 40 students enrolled in upper level foreign language literary/cultural studies content courses showed evidence of incidental language learning over the course of a semester. Students completed a cloze passage and provided both writing and speaking samples at the beginning and end of the semester. In addition, they completed questionnaires related to their goals and perceived development, and instructors were interviewed and observed at various intervals throughout the semester. Instructors' focus was primarily on the content; focus on language was secondary and dealt with incidentally. Some positive evidence of language learning was found, but was mostly limited to students' writing. Speaking abilities, on the other hand, showed little evidence of significant improvement, and global proficiency, as measured by the cloze test, improved in some cases but not in others. Thus, there is some evidence for incidental language learning, but the question remains whether more could have been accomplished. It is suggested that an approach that more intentionally integrates content and language may meet the needs of a greater number of learners and maximize the potential for more language development. [ABSTRACT FROM AUTHOR]

Although N-acetylaspartate (NAA) has long been recognized as the most abundant amino acid in neurons by far, its primary role has remained a mystery. Based on its unique tertiary structure, we explored the potential of NAA to modulate aggregation of amyloid-beta (Aβ) peptide 1–42 via multiple corroborating aggregation assays along with electron microscopy. Thioflavin-T fluorescence assay demonstrated that at physiological concentrations, NAA substantially inhibited the initiation of Aβ fibril formation. In addition, NAA added after 25 minutes of Aβ aggregation was shown to break up preformed fibrils. Electron microscopy analysis confirmed the absence of mature fibrils following NAA treatment. Furthermore, fluorescence correlation spectroscopy and dynamic light scattering measurements confirmed significant reductions in Aβ fibril hydrodynamic radius following treatment with NAA. These results suggest that physiological levels of NAA could play an important role in controlling Aβ aggregation in vivo where they are both found in the same neuronal compartments.

A quasiharmonic analysis (QHA) method is used to compare the potential energy landscapes of dihydrofolate reductase (DHFR) from a piezophile (pressure-loving organism), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec). The QHA method considers atomic fluctuations of the protein as motions of an atom in a local effective potential created by neighboring atoms and quantitates it in terms of effective force constants, isothermal compressibilities, and thermal expansivities. The analysis indicates that the underlying potential energy surface of MpDHFR is inherently softer than that of EcDHFR. In addition, on picosecond time scales, the energy surfaces become more similar under the growth conditions of Mp and Ec. On these time scales, DHFR behaves as expected; namely, increasing temperature makes the effective energy minimum less steep because thermal fluctuations increase the available volume, whereas increasing pressure steepens it because compression reduces the available volume. Our longer simulations show that, on nanosecond time scales, increasing temperature has a similar effect as on picosecond time scales because thermal fluctuations increase the volume even more on a longer time scale. However, these simulations also indicate that, on nanosecond time scales, pressure makes the local potential less steep, contrary to picosecond time scales. Further examination of the QHA indicates the nanosecond pressure response may originate at picosecond time scales at the exterior of the protein, which suggests that protein-water interactions may be involved. The results may lead to understanding adaptations in enzymes made by piezophiles that enable them to function at higher pressures.

OBJECTIVE To explore older adolescents' reflective and impulsive thoughts about health- and social/appearance-related physical activity (PA) outcomes and investigate how those thoughts relate to their PA behavior. PARTICIPANTS One hundred and forty-four undergraduate students (109 women; 35 men) aged 17-19 years (M = 18.11, SD = 0.65) participated in this study in October 2015. METHODS Participants completed a Go/No-go Association Task that assessed automaticity of associations between PA words and either health outcomes or social/appearance outcomes. Questionnaires assessing PA behavior, attitudes, outcome expectations, and body image were also completed. RESULTS Participants demonstrated a positive automatic association between PA and social/appearance outcomes, F(1, 136) = 4.403, p < .05, η2 = .031, but they showed no difference in their associations between PA and desirable or undesirable health outcomes, F(1, 136) = 2.405, p = .123, η2 = .017. CONCLUSIONS Older adolescents implicitly attend to the social/appearance outcomes of PA more than potential health outcomes, indicating that social recognition and a desirable physique may be the key PA motivators for adolescents.

A central challenge in conserving biodiversity is predicting the consequences of anthropogenic climate change on species’ distributions and persistence. Forced climate change has severely altered thermal regimes in marine and freshwater habitats. Rapid escalations in environmental temperatures may be particularly threatening to ectothermic species (almost all plants, invertebrates, fish, amphibians and reptiles), where body temperature and concomitant functional performance are strongly tied to the thermal environment. The threat of overheating is salient for air-breathing, ectothermic divers, such as the estuarine crocodile (Crocodylus porosus, Schneider, 1801), because submergence times are inversely related to water temperature. It is unknown how C. porosus will fare in warming waters but diving oxygen stores are hypothesised to be consumed more rapidly at elevated temperatures leading to a reduction of aerobic dive limits (i.e. maximum submergence time before lactate is accumulated). Shorter dive durations may force animals to spend more time at the water surface, leaving less time available for obligate underwater activities (e.g. predator avoidance and hunting for aquatic prey).This thesis assessed the effect of elevated water temperatures (emulating climate change scenarios) on the diving physiology and behaviour of C. porosus. The thermal sensitivity of predator avoidance dives (i.e. minutes submerged) was assessed in juveniles at three water temperatures reflecting climate change scenarios (Chapter 2). Diving performance was thermally sensitive with dive durations halving between the ‘no warming’ and ‘moderate warming’ scenarios. Ectotherms are however revered for their thermal acclimation/acclimatisation capacity following long term exposure to novel temperatures; whereby an animal’s underlying physiology is responsively altered to maintain or optimise performance. For this reason, the acclimation capacity of C. porosus was assessed by exposing crocodiles to thermal acclimation treatments for a minimum of 30 days. Thermal acclimation treatments had no effect on dive durations - a result indicative of absent thermal acclimation capacity at elevated temperatures within 30 days. The physiological mechanisms underlying compromised diving performance at elevated temperatures were subsequently examined (Chapter 3). Reduced diving performance was hypothesised to be linked to increased oxygen demands and a reduced capacity for metabolic depression at elevated temperatures. Diving oxygen uptake, diving heart rate and post-dive plasma-lactate concentrations were assessed at two test temperatures (i.e. 28◦C and 34◦C). Diving metabolic rate increased threefold between 28◦C and 34◦C and the capacity to depress metabolic demands (from surface levels) was inhibited by 46%. Post-dive plasma-lactate accumulation was independent of water temperature. Collectively, these results show the aerobic dive limit of C.porosus was significantly reduced at elevated temperatures and animals behaviourally terminated dives earlier rather than increasing reliance on anaerobic metabolism.The thermal sensitivity and plasticity of aerobic capacity in juvenile C. porosus was examined and compared to diving oxygen uptake rate (O2DIVE), to assess if diving performance is constrained by aerobic capacity (Chapter 4). Resting (O2STANDARD) and maximum (O2MAX) rates of oxygen consumption were measured and absolute aerobic scope (AAS = O2MAX -O2STANDARD) was calculated. Resting rates of oxygen consumption increased markedly between 28 - 36◦C and did not differ between thermal acclimation treatments. In contrast, O2MAX was thermally insensitive but phenotypically plastic; warm-acclimated animals exhibited a twofold increase in O2MAX compared to animals acclimated to 28◦C. Absolute aerobic scope maintained a broad plateau of thermal independence between 28 - 36◦C and increased in warm-acclimated animals due to elevated O2MAX.The thermal sensitivity of O2DIVE (Q10 = 7.4) was threefold greater than O2STANDARD (Q10 = 2.28), and thermal thresholds marking decrements in diving performance did not align with reductions in aerobic capacity. Together, these findings suggest assessing the vulnerability of diving ectotherms based solely on aerobic scope measurements underestimates susceptibility.Lastly, diving behaviour of adult, free-ranging C. porosus inhabiting the Wenlock River in Cape York (Queensland, Australia) was examined to gauge the influence of seasonal thermal fluctuations (Chapter 5). Satellite and acoustic transmitters with wetdry and pressure sensors were attached/surgically implanted in 24 animals, and diving behaviour was logged throughout August – December 2015. Aerobic dive limits were estimated (cADL) for animals in the coldest and warmest month, and compared to observed submergence times. Dive durations were inversely related to water temperature, with mean and maximum dive durations reducing by 40% and 18%, respectively. A greater percentage of maximum dives exceeded cADLs in December (27.4%) compared to August (18.7%). These results suggest the aerobic dive capacity of C. porosus is influenced by present-day seasonal thermal increases.This body of work highlights a previously overlooked threat to ectothermic divers- climate change. My findings reveal that thermal acclimation is unlikely to buffer estuarine crocodiles from the negative consequences of elevated temperatures on dive capacity. Reduced dive durations may see time available for underwater activities cut short and forced time at the water surface may increase the conspicuousness of hatchlings and juveniles to predators. If the findings here apply to other air-breathing diving ectotherms, obligate underwater activities of this group will likely experience serious disruption under climate warming.

Background: Ethnic minority groups including Asians in Canada have different knowledge and perceptions of heart disease and breast cancer compared with the ethnic majority group. Aim: Examine relationships between perceptions of heart disease and breast cancer, and lifestyle behaviors for Canadian women with British and with South Asian ancestry. Methods: Women with South Asian ( n = 170) and with British ( n = 373) ancestry ( Mage = 33.01, SD = 12.86) reported leisure time physical activity, intended fruit and vegetable consumption, disease perceptions (ability to reduce risk, control over getting the diseases, and influence of family history), and demographic information. Mann–Whitney tests and multiple hierarchical linear regressions were used to examine the relationships between lifestyle behaviors and disease perceptions, with ancestry explored as a possible moderator. Results: Participants with South Asian ancestry believed they had greater ability to reduce their risk and have control over getting breast cancer than participants with British ancestry. Family history influences on getting either disease was perceived as higher for women with British ancestry. Age was positively related to all three perceptions in both diseases. Intended fruit and vegetable consumption was positively related to perceptions of ability to reduce risk and control of both diseases, but was stronger for women with South Asian ancestry regarding perceptions of breast cancer. Leisure time physical activity was positively related to perceptions of control over getting heart disease for women with British ancestry. Conclusions: Women’s disease perceptions can vary by ancestry and lifestyle behaviors. Accurate representation of diseases is essential in promoting effective preventative behaviors.

Introduction: Ischemic stroke is a common injury of the CNS, resulting in neuronal death and impaired brain function, likely contributing to long-term disability in adults. The lack of pharmacological interventions for patients with impairments in stroked-injured brain regions signals need for new strategies aimed at restoring function to the post-ischemic brain. Neurogenesis involves the generation of newborn neurons and occurs throughout life in the mammalian brain, making it an appealing target for potential interventions to enhance post-stroke recovery. Stroke-induced neurogenesis in adult mice has been reported to involve vigorous proliferation and migration of neural progenitors, but most cells die rapidly and fail to repopulate damaged areas. We tested the hypothesis that cortical neurogenesis is enhanced in the immature brain. Methods: We compared juvenile (P20-25) and adult (P60) mice following 45min transient middle cerebral artery occlusion (MCAo). Neurogenesis was examined with immunohistochemistry, including bromodeoxyuridine (BrdU) labeling and cell-type specific markers at 24hr, 7d, and 30d. Post-ischemic neurobehavioral outcomes were assessed at baseline, 7d, and 30d. Results and Conclusions: Despite extensive neuronal cell death in the injured cortex of both age groups at acute time points (24hr and 7d), a remarkable regenerative response was found at 30d, with substantially more mature newborn neurons found in juveniles than adults. Behavioral tests revealed reductions in affected limb use and general motor functioning in MCAo-injured adults and juveniles at 7d, with only the juveniles returning to near baseline levels on most tasks by 30d. When neurogenesis was arrested with ionizing radiation, 30d behavioral recovery was lost. Evidence of cortical neurogenesis is scarce; however, we discovered that newborn neurons in the developing brain not only survive, but post-stroke behavioral outcomes are only improved in non-irradiated juvenile mice. These results provide support for cortical neurogenesis, neuronal replacement, and enhanced functional recovery following stroke, which may have major biological significance for endogenous recovery and repair following CNS damage.

Background The purpose of this research was to examine the relationships of self-reported physical activity to involvement with messages that discuss the prevention of heart disease and breast cancer through physical activity, the explicit believability of the messages, and agreement (or disagreement) with specific statements about the messages or disease beliefs in general. Methods A within subjects’ design was used. Participants (N = 96) read either a breast cancer or heart disease message first, then completed a corresponding task that measured agreement or disagreement and confidence in the agreement or disagreement that 1) physical activity ‘reduces risk/does not reduce risk’ of breast cancer or heart disease, 2) that breast cancer or heart disease is a ‘real/not real risk for me’, 3) that women who get breast cancer or heart disease are ‘like/not like me’, and 4) that women who get breast cancer or heart disease are ‘to blame/not to blame’. This task was followed by a questionnaire measuring message involvement and explicit believability. They then read the other disease messages and completed the corresponding agreement and confidence task and questionnaire measures. Lastly, participants completed a questionnaire measuring physical activity related attitudes and intentions, and demographics. Results There was no difference in message involvement or explicit believability of breast cancer compared to heart disease messages. Active participants had a higher confidence in their agreement that physical activity is preventive of heart disease compared to breast cancer. Multinomial regression models showed that, in addition to physical activity related attitudes and intentions, agreement that physical activity was preventive of heart disease and that women with heart disease are ‘like me’ were predictors of being more active compared to inactive. In the breast cancer model only attitudes and intentions predicted physical activity group. Conclusions Active women likely internalized messages about heart disease prevention through physical activity, making the prevention messages more readily available within memory, and active women may therefore process such information differently. The study of how health-related beliefs are created and are related to perceptions of prevention messages is a rich area of study that may contribute to more effective health promotion.

© 2018 Elsevier Ltd Human-induced thermal variability can disrupt energy balance and performance in ectotherms; however, phenotypic plasticity may play a pivotal protective role. Ectotherm performance can be maintained in thermally heterogeneous habitats by reducing the thermal sensitivity of physiological processes and concomitant performance. We examined the capacity of juvenile green sturgeon (Acipenser medirostris) to respond to daily thermal variation. Juveniles (47 days post-hatch) were exposed to either stable (15 ± 0.5 °C) or variable (narrowly variable: 13–17 °C day−1or widely variable 11–21 °C day−1) thermoperiod treatments, with equivalent mean temperatures (15 ± 0.5 °C), for 21 days. Growth (relative growth rate, % body mass gain), upper thermal tolerance (critical thermal maxima, CTMax) and the thermal sensitivity of swimming performance (critical swimming speed, Ucrit) were assessed in fish from all treatments. Accelerated growth was observed in fish maintained under widely variable temperatures compared to narrowly variable and stable temperatures. No significant variation in CTMax was observed among thermoperiod treatments, suggesting all treatment groups acclimated to the mean temperature rather than daily maximums. The widely variable treatment induced a plastic response in swimming performance, where Ucritwas insensitive to temperature and performance was maintained across a widened thermal breadth. Maximum Ucritattained was similar among thermoperiod treatments, but performance was maximised at different test temperatures (stable: 4.62 ± 0.44 BL s−1at 15 °C; narrowly variable: 4.52 ± 0.23 BL s−1at 21 °C; widely variable: 3.90 ± 0.24 BL s−1at 11 °C, mean ± s.e.m.). In combination, these findings suggest juvenile A. medirostris are resilient to daily fluctuations in temperature, within the temperature range tested here.

Background Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer’s long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. Objective For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. Methods We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006–2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. Results We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. Conclusions New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures.

Stem cells (SCs) can self-renew or differentiate into different cell types, which makes them an ideal cell source for therapies based on tissue engineering. Despite these characteristics, the employment of SCs in clinics has seen alternating fortunes because of our limited understanding of the signals governing SC functions and fate, which impairs our ability to engineer systems to deliver SCs in vivo and to guide their correct biological processes. However, experimental evidence demonstrated that SCs are able to recognize biochemical and biophysical signals displayed by material surfaces; most importantly, cells integrate these signals to elaborate fate decisions. Although the mechanisms underlying signal recognition and response have not been thoroughly characterized, there is a general consensus that the cell adhesion process plays a central role. Adhesion represents a communication gate between exogenous signals and intracellular signaling cascades involving the cytoskeleton and the nucleus. In this work we present recent findings on materials engineered to control cell functions through adhesion processes. In particular, we emphasize the role of material signals on SC behavior. Finally, we discuss a few sensing and transductive molecular mechanisms in an effort to draw out unifying elements concerning cell recognition of and reaction to biophysical/biochemical material signals aimed at controlling cell fate through cell adhesion. Microneedles and nanomedicine are two out of several active innovative approaches used to enhance the transdermal drug and vaccine delivery. Their application individually or in combination have shown to be very promising and attracted considerable interest by researchers from both industry and academia over the last 2 decades. Combining the two technologies has growing interest and has shown to be promising approach not only in enhancing the transdermal drug and vaccine permeation for even difficult drug molecules, such as hydrophilic and macromolecules, but also impart protection and controlling the drug release rates. In Subchapter 2.2, we aim to highlight the advances, which has been made in using these two technologies as an individual or in combination with drug and vaccine delivery. Metal implants, in the form of screws, plates, or pins, are extensively used in the treatment of fractures and nonunions or as replacements for malfunctioned joints. These bones implants face many challenges for acceptance and survival upon insertion in the human body. These challenges include severe inflammation, bacterial invasion, and poor biointegration with the traumatized tissue. Titania (TiO 2 ) nanotubes (TNTs) arrays engineered on the surface of Ti implants by simple and scalable electrochemical anodization process, which have been widely explored as a new nanoengineering approach to improve the process of osseointegration and at the same time to be used as depots for loading drugs and their controllable release for localized delivery, and therapeutic purpose. Several advanced functions can be introduced into these multifunctional implants, including biopolymers, nanoparticles or external stimulation (e.g., electrical, electromagnetic and ultrasound) to release the loaded therapeutic agents in a desired manner when required. Subchapter 2.3 highlights the developed concepts of drug releasing implants based on TNTs for enhancing osteogenesis at the bone-implant interface, as an alternative approach to systemic delivery of therapeutic agents. The reconstruction of skeletal defects is a continuing challenge. Bone and dentin are mineralized hard tissues. The primary inorganic component of these two tissues is crystalline hydroxyapatite and the primary organic component is type I collagen, and these two components are cell-manufactured materials. Tissue-engineering strategies using novel biomaterials have emerged as a promising potential for the treatment of mineralization defects. Some of the recent bioinspired biomaterials utilize proteins and peptides as nanoscale building blocks. A key functional property is that biomaterials need to be cell-compatible and mimic the dynamic nature of the extracellular matrix. ECM is a complex environment comprising a plethora of macromolecules. Another class of novel biomaterials that are currently being developed are peptide-based hydrogels. Peptide-based engineered scaffolds present several advantages over traditional protein scaffolds as the control over hydrogel properties and can be easily tailored to the requirement of the tissue. Biomaterials generated by the self-assembly process have varied applications as it mimics nature’s method of material synthesis. Therefore, concepts of protein-based self-assembly can be utilized for constructing useful biomaterials.

Mate selection in heterogeneous sensory environments may be challenging. Assessing the suitability of potential partners may be compromised if individual characteristics cannot be assessed reliably across all encountered conditions. The problem is particularly acute in a species recognition context if matings with heterospecific partners yield lower fitness than matings with conspecific partners of low quality. Multimodal communication may circumvent this problem by transmitting redundant information on several channels that are not affected by the same degradation processes (Backup hypothesis). We addressed this issue in two hybridizing newts (Lissotriton helveticus and L. vulgaris) for which visual species recognition is disrupted in water stained by humic acids, a common family of compounds produced by decaying vegetation. Because these species also use olfaction for sexual communication, we predicted that species recognition was maintained in stained water when olfactory information was available. Results did not support the prediction of the backup hypothesis. Species recognition was observed in the clear water treatment only, and the olfactory channel seemed to carry only limited additional information. Two mechanisms may account for the small contribution of olfaction to species recognition. (1) Females may have a lower sensory capacity to discriminate between olfactory than between visual signals. (2) Divergence between olfactory signals may be lower than divergence between visual signals. Resorting to multimodal communication does not seem to allow efficient discrimination across all environmental conditions. Therefore, we predict that hybridization rate would vary between habitats depending on water color.

Despite selection pressures on prey animals to maintain phenotypically homogeneous groups, variation in phenotype within animal groups is commonly observed. Although many prey animals preferentially associate with size-matched individuals, a lack of preference or a preference for nonmatching group mates is also commonly observed. We suggest that the assortative response to predation risk may be mediated by body size because larger bodied prey may be at greater risk of predation than smaller bodied prey when in a mixed group due to their greater potential profitability. We test this idea by observing attacks by three-spine sticklebacks Gasterosteus aculeatus on mixed groups of large and small Daphnia magna prey. We find that smaller Daphnia are at greatest risk when they form the majority of the group, whereas larger Daphnia are at the greatest predation risk when they form the minority. Thus, we predict that both large and small prey should benefit by association with large prey, generating a potential conflict over group membership that may lead to the mixed phenotype groups we observe in nature.

The current study focuses on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. In light of recent studies demonstrating delayed GABA antagonists improve motor function, we utilized electrophysiology, biochemistry and neurobehavioral methods to investigate the role of α5 GABAA receptors on hippocampal plasticity and functional recovery following ischemic stroke. Male C57Bl/6 mice were exposed to 45 min transient middle cerebral artery occlusion and analysis of synaptic and functional deficits performed 7 or 30 days after recovery. Our findings indicate that hippocampal long-term potentiation (LTP) is impaired 7 days after stroke and remain impaired for at least 30 days. We demonstrate that ex vivo administration of L655,708 reversed ischemia-induced plasticity deficits and importantly, in vivo administration at delayed time-points reversed stroke-induced memory deficits. Western blot analysis of hippocampal tissue reveals proteins responsible for GABA synthesis are upregulated (GAD65/67 and MAOB), increasing GABA in hippocampal interneurons 30 days after stroke. Thus, our data indicate that both synaptic plasticity and memory impairments observed after stroke are caused by excessive tonic GABA activity, making inhibition of specific GABA activity at delayed timepoints a potential therapeutic approach to improve functional recovery and reverse cognitive impairments after stroke.

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb

The Title 10 of the Code of Federal Regulations (10 CFR) Part 52 process and unique aspects of a passive plant design have presented new challenges for the development and implementation of the American Society of Mechanical Engineers (ASME) Code for Operation and Maintenance of Nuclear Power Plants (OM Code) requirements. This paper will discuss lessons learned from the development and implementation of pre-service testing (PST) / in-service testing (IST) program plans for the AP1000® plant, for both international and domestic. Topics to be addressed include the following: • Level of detail in design certification • Treatment of unique passive plant features • Design certification commitments beyond Code requirements • Future regulatory requirements for high-risk non-safety component PST/IST • Implementation challenges for international plants Paper published with permission.

Genetically inherited absence epilepsy in humans is typically characterized by brief (seconds) spontaneous seizures, which involve spike–wave discharges (SWDs) in the EEG and interruption of consciousness and ongoing behavior. Genetic (inbred) models of this disorder in rats have been used to examine mechanisms, comorbidities, and antiabsence drugs. SWDs have also been proposed as models of complex partial seizures (CPSs) following traumatic brain injury (post-traumatic epilepsy). However, the ictal characteristics of these rat models, including SWDs and associated immobility, are also prevalent in healthy outbred laboratory rats. We therefore hypothesized that SWDs are not always associated with classically defined absence seizures or CPSs. To test this hypothesis, we used operant conditioning in male rats to determine whether outbred strains, Sprague Dawley and Long–Evans, and/or the inbred WAG/Rij strain (a rat model of heritable human absence epilepsy) could exercise voluntary control over these epileptiform events. We discovered that both inbred and outbred rats could shorten the duration of SWDs to obtain a reward. These results indicate that SWD and associated immobility in rats may not reflect the obvious cognitive/behavioral interruption classically associated with absence seizures or CPSs in humans. One interpretation of these results is that human absence seizures and perhaps CPSs could permit a far greater degree of cognitive capacity than often assumed and might be brought under voluntary control in some cases. However, these results also suggest that SWDs and associated immobility may be nonepileptic in healthy outbred rats and reflect instead voluntary rodent behavior unrelated to genetic manipulation or to brain trauma. SIGNIFICANCE STATEMENT Our evidence that inbred and outbred rats learn to control the duration of spike–wave discharges (SWDs) suggests a voluntary behavior with maintenance of consciousness. If SWDs model mild absence seizures and/or complex partial seizures in humans, then an opportunity may exist for operant control complementing or in some cases replacing medication. Their equal occurrence in outbred rats also implies a major potential confound for behavioral neuroscience experiments, at least in adult rats where SWDs are prevalent. Alternatively, the presence and voluntary control of SWDs in healthy outbred rats could indicate that these phenomena do not always model heritable absence epilepsy or post-traumatic epilepsy in humans, and may instead reflect typical rodent behavior.

Using examples from the Permian Basin of Texas, the North Slope of Alaska, and the Bergan Field of Kuwait, this paper describes how oil geochemical fingerprinting can be applied to diagnose quickly and easily three production problems that may affect highly deviated wells. High-Resolution Gas Chromatography can be used to quantify ~1,000 different compounds in an oil, and the relative abundances of those compounds form a geochemical fingerprint. Geochemical differences between fluids in adjacent reservoirs can serve as natural tracers for fluid origin, allowing changes in production in highly deviated wells to be understood. Application 1: In wells that are fracture stimulated, oil fingerprinting can be used to assess whether induced fractures have propagated out of the target interval and into overlying or underlying formations. Oil fingerprinting can be used to quantify what percentage of the produced oil and gas is coming from each interval and how the effective stimulated rock volume changes through time. This concept is illustrated here with a Permian Basin example. Application 2: In wells with multiple laterals in the same well (such as those in certain North Slope, Alaska fields), sand can settle out of the production stream and form sand bridges that obstruct production from one or more of the laterals. In addition, sand co-produced with oil from shallower laterals can settle at the bottom of the vertical section during regular production and obstruct the entry to a deeper lateral. Geochemical fingerprinting can be used to determine quantitatively the contribution of each of several zones to a commingled oil stream. This technique allows the operator to identify sanded-out intervals for fill cleanout (FCO). Application 3: If two reservoirs are both oil bearing, but are of very different permeability, horizontal wells with an intended landing target in the tighter reservoir may be adversely affected if the well path contacts the more permeable reservoir. The Mauddud reservoir in Kuwait provides examples of this phenomenon. The Mauddud carbonate occurs between two massive clastic reservoirs, the Wara and the Burgan. Average Mauddud porosity is 18% with low permeability (1-10 mD), characteristics which make this reservoir a candidate for horizontal drilling. However, some lateral wells in this carbonate may encounter the adjacent, more permeable reservoirs over a short portion of the well path. In such cases, production from the adjacent reservoir may account for virtually all of the well's production, even though the well was intended to be completed solely in the tighter reservoir. Oil fingerprinting can be used to identify wells affected by this problem. A common theme unifies these three applications: Geochemical differences between in-situ fluids in adjacent reservoirs can serve as natural tracers for fluid movement. However, these techniques have been under-applied as tools for optimization of production from highly deviated wells. This paper illustrates the application of this technology to that well type in a variety of play types.

We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

Furniture flammability standards are typically met with chemical flame retardants (FRs). FRs can migrate out of products into dust and are linked to cancer, neurological impairment, and endocrine disruption. We collected 95 dust samples from dormitory common areas and student rooms on two U.S. college campuses adhering to two different furniture flammability standards: Technical Bulletin 117 (TB117) and Technical Bulletin 133 (TB133). Because TB133 requires furniture to withstand a much-more-demanding test flame than TB117, we hypothesized that spaces with TB133 furniture would have higher levels of FRs in dust. We found all 47 targeted FRs, including 12 polybrominated diphenyl ether (PBDE) congeners, 19 other brominated FRs, 11 phosphorus FRs (PFRs), 2 Dechlorane-Plus (DP) isomers, and 3 hexabromocyclododecane (HBCDD) isomers in the 95 dust samples. We measured the highest reported U.S. concentrations for a number of FRs, including BDE 209 (up to 990 000 ng/g), which may be used to meet the TB133 standard. We prioritized 16 FRs and analyzed levels in relation to flammability standard as well as presence and age of furniture and electronics. Adherence to TB133 was associated with higher concentrations of BDE 209, decabromodiphenylethane (DBDPE), DPs, and HBCDD compared to adherence to TB117 in univariate models (p < 0.05). Student dormitory rooms tended to have higher levels of some FRs compared to common rooms, likely a result of the density of furniture and electronics. As flammability standards are updated, it is critical to understand their impact on exposure and health risks.

Inflammatory signals present in demyelinated multiple sclerosis lesions affect the reparative remyelination process conducted by oligodendrocyte progenitor cells (OPCs). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)–6 have differing effects on the viability and growth of OPCs, however the effects of IL-17A are largely unknown. Primary murine OPCs were stimulated with IL-17A and their viability, proliferation, and maturation were assessed in culture. IL-17A-stimulated OPCs exited the cell cycle and differentiated with no loss in viability. Expression of the myelin-specific protein, proteolipid protein, increased in a cerebellar slice culture assay in the presence of IL-17A. Downstream, IL-17A activated ERK1/2 within 15 min and induced chemokine expression in 2 days. These results demonstrate that IL-17A exposure stimulates OPCs to mature and participate in the inflammatory response.

CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioid-induced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (−)-morphine or its mu opioid receptor (MOR)-inactive metabolite morphine-3-glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated nuclear factor kappaB (NF-κB), increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E2 (PGE2) from these cells. (−)-Morphine-induced upregulation of TNFα mRNA and PGE2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to have both MOR- and TLR4-activity), suggestive of an interplay between MOR and TLR4 co-activation by (−)-morphine. In support, MOR-dependent Protein Kinase A (PKA) opposed TLR4 signaling, as PKA inhibition (H-89) also unmasked (−)-morphine-induced TNFα and COX2 mRNA upregulation. Intrathecal injection of CNS endothelial cells, stimulated in vitro with M3G, produced TLR4-dependent tactile allodynia. Further, cortical suffusion with M3G in vivo induced TLR4-dependent vasodilation. Finally, endothelial cell TLR4 activation by lipopolysaccharide and/or M3G was blocked by the glial inhibitors AV1013 and propentofylline, demonstrating endothelial cells as a new target of such drugs. These data indicate that (−)-morphine and M3G can activate CNS endothelial cells via TLR4, inducing proinflammatory, biochemical, morphological, and behavioral sequelae. CNS endothelial cells may have previously unanticipated roles in opioid-induced effects, in phenomena blocked by presumptive glial inhibitors, as well as TLR4-mediated phenomena more broadly.

This article examined the conceptual and statistical distinction between perceived competence and self-efficacy. Although they are frequently used interchangeably, it is possible that distinguishing them might assist researchers in better understanding their roles in developing enduring adaptive behavior patterns. Perceived competence is conceived in the theoretical framework of self-determination theory and self-efficacy is conceived in the theoretical framework of social-cognitive theory.The purpose of this study was to empirically distinguish perceived competence from self-efficacy for exercise.Two studies evaluated the independence of perceived competence and self-efficacy in the context of exercise. Using 2 extant instruments with validity and reliability evidence in exercise contexts, the distinctiveness of the 2 constructs was assessed in 2 separate samples (n = 357 middle-aged sedentary adults; n = 247 undergraduate students).Confirmatory factor analysis supported the conceptual and empirical distinction of the 2 constructs.This study supports the conceptual and statistical distinction of perceived competence from perceived self-efficacy. Applications of these results provide a rationale for more precise future theorizing regarding their respective roles in supporting initiation and maintenance of health behaviors.

The authors use the Freelancers Union's annual Independent Worker Survey (IWS) from 2007 to 2011, the union's administrative membership file, and the American Community Survey to estimate the extent to which client nonpayment of independent workers is a problem and the ability of a written contract to reduce the odds of nonpayment. They develop tests for nonresponse and sample selection biases, although due to a lack of instrumental variables and contract endogeneity, they must speculate on the size of the bias. They find that contract use is associated with income that is 13.7% higher (for New York State respondents 21.7% higher) than income produced without a contract. They also find that contract use reduces nonpayment; however, even when a contract is used, 38.8% of respondents still had trouble getting paid: One-third were paid late, and 10% were either paid less than the agreed upon amount or were never paid.