cssi/SciSciGPT-SciSciNet huggingface dataset:
Why Don't We Have Proven Treatments for HFpEF?

The lack of effective treatments for heart failure with preserved ejection fraction represents a large and growing unmet need in cardiology today. A critical obstacle to therapeutic innovation in heart failure with preserved ejection fraction has been the absence of animal models that accurately recapitulate the complexities of the human disease. Here, we propose that more comprehensive multi organ system and functional phenotyping of preclinical models is essential if we are to maximize our chances of discovering and validating novel targets for effective therapeutic development in heart failure with preserved ejection fraction . At this time in human history, we are witnessing an unprecedented aging of populations around the world. By 2050, the number of individuals >65 years will nearly triple to ≈1.5 billion, accounting for ≈16% of the world’s population.1 Although cardiology, and medicine more generally, can appropriately take enormous pride in the progress made in extending human lifespan, we must also recognize that as our populations age, so will the clinical landscape. Perhaps the quintessential example of how the evolution of human longevity is changing the face of medicine is the emerging epidemic of heart failure with preserved ejection fraction (HFpEF). Often described as a disease of the elderly, trends in HFpEF have closely paralleled the change in global ageing demographics. In the United States, the prevalence of HFpEF, relative to heart failure with reduced ejection fraction (HFrEF), is increasing at an alarming rate of 1%/y with the overwhelming majority of patients being >65 years.2 Importantly, the prognosis for HFpEF remains poor with mortality rates comparable with HFrEF.2 Unfortunately, although tremendous strides have been made in improving mortality in HFrEF, no pharmacological therapy, including our armament of neurohormonal antagonists, has demonstrated similar benefits in HFpEF. In fact, no large-scale clinical trial of medical therapy has …
A phylogenetic analysis of the genus Carica L. (Caricaceae) based on restriction fragment length variation in a cpDNA intergenic spacer region

The phylogenetic relationships among twelve wild and cultivated species of Carica (Caricaceae) were analyzed using restriction fragment length variation in a 3.2-kb PCR amplified intergenic spacer region of the chloroplast DNA. A total of 138 fragments representing 137 restriction sites accounting for 5.8% of the amplified region were examined. Both parsimony and neighbor joining cluster analyses confirmed the close association among South American wild Carica species. However, cpDNA data did not support the traditional monophyly hypothesis for the evolution of Carica. Further, cpDNA analyses showed two basic evolutionary lineages within the genus Carica, one defined by cultivated C. papaya and another consisting of the remaining wild species from South America in a well resolved but poorly supported monophyletic assemblage. This evolutionary split in Carica strongly suggests that C. papaya diverged from the rest of the species early in the evolution of the genus and evolved in isolation, probably in Central America.
The Treatment Journey in Epilepsy: Part 2:Tipping Points in Surgical Decision-Making (P6.352)

OBJECTIVES: To explore how patients with refractory focal epilepsy explain the personal process of seeking care and considering surgery as a treatment alternative. BACKGROUND: Epilepsy surgery offers an effective opportunity for the cure of focal seizures. Patients and referring physicians hesitate to consider surgical options despite technical advances. How to communicate evidence of the benefits of surgery presents a challenge to the professional community. Using qualitative research, we sought to explore patient-related decisional tipping points in the process of moving care forward. METHODS: Personal semi-structured interviews were done in two groups of patients with focal uncontrolled seizures: those undergoing a pre-surgical evaluation (n=16) and those who had consented for epilepsy surgery (n=20). The mean age of participants was 36 years and the mean duration of refractory seizures was 16 years. RESULTS: Surgical decision-making did not occur in a vacuum but occurred in the context of seizure experience, life experience, developmental stage, and belief systems. Consenting for surgery reflects a conceptual tipping point in the minds of patients. It is centered on the perception of urgently needing to make treatment changes that will pave the way to living a “normal life”. Surgical decision-making takes time and courage and involves patients and their support networks. Decision-making is an active process of information gathering, building confidence and making the decision. CONCLUSIONS: Many life years are lost to undertreated seizures. Understanding the processes framing treatment decisions contributes to identifying practical solutions to bridging treatment gaps including: 1) addressing public and professional ignorance about the likely course of refractory epilepsy, 2) discouraging treatment inertia and 3) encouraging patient self advocacy. Disclosure: Dr. Dewar has nothing to disclose. Dr. Ranit has nothing to disclose. Dr. Pieters has nothing to disclose.
Impact of bariatric surgery on outcomes of patients with nonalcoholic fatty liver disease: a nationwide inpatient sample analysis, 2004–2012

Abstract Background Bariatric surgery in eligible morbidly obese individuals may improve liver steatosis, inflammation, and fibrosis; however, population-based data on the clinical benefits of bariatric surgery in patients with nonalcoholic fatty liver disease (NAFLD) are lacking. Objectives To assess the relationship between bariatric surgery and clinical outcomes in hospitalized patients with NAFLD. Setting United States inpatient care database. Methods The Nationwide Inpatient Sample database was queried from 2004 to 2012 with co-diagnoses of NAFLD and morbid obesity. Hospitalizations with a history of prior bariatric surgery (Roux-en-Y gastric bypass, gastric band, and sleeve gastrectomy) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes included cirrhosis, myocardial infarction, stroke, and renal failure. Poisson regression was used to derive adjusted incidence risk ratios for clinical outcomes in patients with prior bariatric surgery compared with those without bariatric surgery. Results Among 45,462 patients with a discharge diagnosis of NAFLD and morbid obesity, 18,618 patients (41.0%) had prior bariatric surgery. There was a downward trend in bariatric surgery procedures (percent annual change of −5.94% from 2004 to 2012). In a multivariable analysis, prior bariatric surgery was associated with decreased inpatient mortality compared with no bariatric surgery (incidence risk ratios=.08; 95% confidence interval, .03–.20, P P Conclusions Prior bariatric surgery is associated with decreased in-hospital morbidity and mortality in morbidly obese NAFLD patients. Despite this, the proportion of NAFLD patients with bariatric surgery has declined from 2004 to 2012.
Enzymatic Assays to Investigate Acyl-Homoserine Lactone Autoinducer Synthases

Bacteria use chemical molecules called autoinducers as votes to poll their numerical strength in a colony. This polling mechanism, commonly referred to as quorum sensing, enables bacteria to build a social network and provide a collective response for fighting off common threats. In Gram-negative bacteria, AHL synthases synthesize acyl-homoserine lactone (AHL) autoinducers to turn on the expression of several virulent genes including biofilm formation, protease secretion, and toxin production. Therefore, inhibiting AHL signal synthase would limit quorum sensing and virulence. In this chapter, we describe four enzymatic methods that could be adopted to investigate a broad array of AHL synthases. The enzymatic assays described here should accelerate our mechanistic understanding of quorum-sensing signal synthesis that could pave the way for discovery of potent antivirulence compounds.
High vacuum and aspiration on phacoemulsification efficiency and chatter for Centurion.

Abstract Objective To compare relative efficiency and chatter of high aspiration and vacuum settings. Design In vitro laboratory study. Methods The John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, was the study setting. Porcine nuclei were fixed in formalin and cut into 2.0 mm cubes. Lens cubes were phacoemulsified with Balanced tips at 50 and 60 mL/min aspiration with 500, 600, and 700 mm Hg vacuum with monitored forced infusion. Experiments were conducted at constant torsional power, longitudinal power, and intraocular pressure. Results No significant change was observed in average chatter across each tested setting. Increasing aspiration rate did not increase efficiency. Increasing vacuum up to 600 mm Hg from 500 mm Hg did not change efficiency. However, increasing vacuum to 700 mm Hg decreased efficiency (p = 0.008 for 500 mm Hg vs 700 mm Hg and p = 0.05 for 600 mm Hg vs 700 mm Hg). Increasing aspiration and increasing vacuum did not significantly improve chatter. Conclusions Increasing aspiration above 50 mL/min did not improve phacoemulsification efficiency. Increasing vacuum settings to 700 mm Hg decreases efficiency. Chatter did not significantly change with increasing aspiration and vacuum settings.
The semantics of event prevention

In planning tasks an agent may often find himself in a situation demanding that he choose an action that would prevent some unwanted event from occurring. Similarly, in tasks involving the generation of descriptions or explanations of sequences of events, it is often useful to draw as many informative connections as possible between events in the sequence; often, this means explaining why certain events are not possible. In this paper, I consider the semantics of event prevention and argue that a naive semantics which equates prevention with the elimination of all future possibility of the event in question is often difficult, if not impossible, to implement. I argue for a more useful semantics which falls out of some reasonable assumptions regarding restrictions on the set of potential actions available to an agent: (1) those actions about which the agent has formed intentions, (2) those actions consistent with the agent's attitudes (including its other intentions), and (3) the set of actions evoked by the type of situation in which the agent is embedded.
Predictors of hepatitis B immunization status in Korean American children.

This study assesses the predictive factors of social context and ethnicity on childhood hepatitis B immunization status among Korean American children living in an urban area. Logistic regression analysis revealed that maternal perceptions of benefits (OR = 3.24, 95% CI = 1.23–9.63) and barriers (OR = 0.4, 95% CI = 0.25–0.89) were important predictors of hepatitis B immunization status. Among children ages 2–5 years in this study, children born prior to the adoption of new immunization guidelines in 1994 were less likely to have received all three doses of hepatitis B vaccine (adjusted OR = 0.69, 95% CI = 0.43–0.80). An informal social support network providing information concerning parenting and health care of children was also associated with an increased probability of obtaining the immunization (adjusted OR = 2.76, 95% CI = 1.25–7.66). Mother's history of adequate prenatal care (χ2 = 3.98, p < 0.05) was significantly related to immunization status. Major perceived barriers in accessing preventive health care include burden of cost, language barrier, and difficulty remembering the immunization schedule.
A number theory approach to problem representation and solution

A number theory approach to problem solving is presented using the tower of cubes puzzle as an example. Some conventional methods of solving the puzzle are first discussed. The puzzle is then thoroughly studied using an entirely different approach. Special numbers are used to represent the different colors on the sides of the cubes. A description matrix is used to compress the problem representation. The solution method becomes very efficient because of the concise representation of the problem. Two theorems are developed to verify the solution method. A generalization of the puzzle is also discussed.
Defining nature. Competing perspectives: between nativism and ecological novelty

In the 1980s, three sub-disciplines of ecology emerged – restoration ecology, conservation biology, and invasion biology – and all three embraced the nativism paradigm. By the early 2000s, historians, sociologists, and philosophers interested in the development of science began to examine the growing field of invasion biology and usually were critical of it. In the past few years, a new perspective has been taking hold in the field of ecology. Referred to as ecological novelty it emphasizes that many factors are producing ecologically novel environments. A much more simply descriptive concept, it is currently competing with the nativism paradigm to define nature . Whether the nativism or ecological novelty paradigm emerges as the dominant perspective going forward will determine how nature and biodiversity are managed.
Medicaid payer status is associated with increased mortality and morbidity after inpatient shoulder arthroplasty: a multistate analysis, 2007-2014.

Background and objectives Inpatient shoulder arthroplasty is widely performed around the USA at an increasing rate. Medicaid insurance has been identified as a risk factor for inferior surgical outcomes. We sought to identify the impact of being Medicaid-insured on in-hospital mortality, readmission, complications, and length of stay (LOS) in patients who underwent inpatient shoulder arthroplasty. Methods We analyzed 89 460 patient discharge records for inpatient total, partial, and reverse shoulder arthroplasties using data from the Healthcare Cost and Utilization Project’s State Inpatient Databases for California, Florida, New York, Maryland, and Kentucky from 2007 through 2014. We compared patient demographics, present-on-admission comorbidities, and hospital characteristics by insurance payer. We estimated multilevel mixed-effect multivariate logistic regression models and generalized linear models to assess insurance’s effect on in-hospital mortality, readmission, infectious complications, cardiac complications, and LOS; models controlled for patient and hospital characteristics. Results Medicaid-insured patients had greater odds than patients with private insurance, other insurance, and Medicare of inpatient mortality (OR: 4.61, 95% CI 2.18 to 9.73, p Conclusions Our study supports our hypothesis that among inpatient shoulder arthroplasty patients, those with Medicaid insurance have worse outcomes than patients with private insurance, other insurance, and Medicare. These results are relatively consistent with previous findings in the literature.
Late prehistoric Florida: archaeology at the edge of the Mississippian world / Life among the tides: recent archaeology on the Georgia Bight / New histories of pre-Columbian Florida

Several years ago I asked a press agent whether edited volumes were going the way of the dodo, as I had then recently been told. “Maybe in other disciplines,” they replied, “but archaeologists love...
ALLOW ME TO (RE)INTRODUCE MYSELF: AN EXPERIENTIAL LEARNING REBRANDING PROJECT WITHIN THE CONTEXT OF PROFESSIONAL SPORTS

Rebranding is a widely utilized practice to change the image of a brand in the minds of the consumer through major or minor changes in both its positioning and aesthetics. Yet, evidence suggests it...
Effector T-cell cytolytic activity modules derived from CD3+ single cells from human primary triple-negative breast cancer (TNBC) in multiple solid tumors to predict response to immune checkpoint blockade therapy (ICB).

1073Background: The prognostic and predictive value of tumor infiltrating lymphocytes for ICB has been recognized in a variety of tumor types, including TNBC. Nonetheless, our understanding of the ...
A Note on Min–Max Pair in Tournaments

We prove the following results in this paper. Let T be a tournament of order $$n\ge 3$$ with vertex set V and arc set E, x a vertex of maximum out-degree and y a vertex of minimum out-degree of T. If $$yx\in E$$ then there exists a path of length i from x to y for any i with $$2\le i \le n-1$$ ; and if $$xy\in E$$ , then there exists a path of length i from x to y for any i with $$3\le i \le n-1$$ unless xy is exceptional. We also give a very short discussion to almost regular tournaments and prove a result of Jakobsen.
Study of the Effect and Mechanism of a Cap Layer in Controlling the Statistical Variation of Via Extrusion

This work examines the effect of a metallic cap layer in controlling via extrusion and explores the underlying mechanisms. Ta was deposited as the cap material, which was very effective in reducing the statistical spread of via extrusion. The correlation between extrusion and microstructure of the vias was investigated and compared for the reference uncoated vias and the Ta-capped vias. Thermo-mechanical characterization as well as TEM characterization of the Ta cap/via interface were also carried out. Void formation at grain junctures were observed. The results suggest that mass transport through grain boundaries plays an important role in causing the statistical variation of extrusion, which can be effectively suppressed by the Ta cap. Void formation was also reduced by the cap layer. Additional factors affecting extrusion, including interfacial diffusion and dislocation glide, were also discussed.
GERD, Helicobacter pylori and MGUS-Is There a Relationtionship?.

Background: The prevalence of clinically significant gastro esophageal reflux (GERD) in the general population varies between 3–6%. We have observed GERD to be one of the major complaints of our patient population with monoclonal gammopathy of unknown significance (MGUS). There is no literature available on the incidence of GERD in MGUS. However, there have been conflicting reports on the prevalence of helicobacter pylori (H. pylori) and MGUS. Objective: To study the incidence and relationship of GERD, H. pylori and MGUS. Methods: We identified all patients diagnosed with MGUS at the Kansas City VA Medical Center over the last 20 years. Out of the 417 patients identified with MGUS, 394 patients fulfilled the inclusion criteria. All patients with GERD were evaluated by gastroenterologists at our institution who determined their diagnostic and therapeutic management. Charts on these patients were then reviewed for endoscopic findings, pathological biopsies, H. pylori staining on histology, serum protein electrophoresis with immunofixation (SPEP/IFE), immunoglobulin levels, and bone marrow biopsies. Results: In this study, 41% patients with MGUS were noted to have moderate to severe symptoms of GERD (162/394). The median age of patients with and without GERD was similar (72 versus 71 years). Endoscopies were performed on 60% of the patients with GERD (97 of 162). Histology was positively stained for H. pylori in 27.8% patients (27/97). We did not find any correlation between H. pylori positivity and the type or level of monoclonal protein. In addition, we observed no change in immunoglobulin levels following treatment and eradication of H. pylori. Conclusion: The incidence of GERD is significantly higher in patients with MGUS than in the general population. In our study, no correlation was seen between H. pylori infection and MGUS.
Face Veil Bans in the European Court of Human Rights: The Importance of Empirical Findings

First, this Article will set out the facts and context of face veil bans in Europe and the legal challenges surrounding them. Then, the Article will explain the legal criteria that will be used by the European Court of Human Rights when deciding on this issue. Next, in its central argument, this Article will discuss the possible outcome of S.A.S. v. France, by assessing whether the arguments advanced by European governments to ban face veils can pass the human rights test instituted by the court. This assessment will rely on the court’s case law, as well as on the case file of the case currently pending before it. It will also include the results of empirical research conducted among women wearing face veils in Europe and analyze whether the government’s claims are consistent with those empirical studies.
Direct site endovascular repair as salvage procedure after anastomotic breakdown of primary repair following trauma.

Abstract A 16-year-old boy presented to a level I trauma center after multiple gun shot wounds and a motorcycle crash. He was in profound hemorrhagic shock and had multiple traumatic injuries, including a right common iliac arterial injury. The vessel was shunted for damage control and subsequently repaired primarily. On hospital day 18, he experienced dehiscence of the anastomosis requiring urgent surgery. The artery was ultimately repaired with an expandable polytetrafluoroethylene stent graft deployed in an open fashion through the site of injury. We discuss the use of stent grafts as an interesting alternative to suture repair after anastomotic disruption.
Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting gastrointestinal neoplasia of the colon, expanded experience and follow-up

Background and study aims Colonic lesions may not be amenable to conventional endoscopic mucosal resection (EMR) due to previous manipulation, submucosal invasion, or lesion flatness. In 2018, we described Dissection-enabled Scaffold Assisted Resection (DeSCAR) to be safe for the endoscopic resection of non-lifting or residual colonic lesions 1 In this study, we expand our original cohort to describe our expanded experience with patients undergoing DeSCAR and assess the efficacy, safety, and feasibility of DeSCAR for endoscopic resection of non-lifting or residual colonic lesions. Patients and methods We retrospectively reviewed 57 patients from 2015–2019 who underwent DeSCAR for colonic lesions with incomplete lifting and/or previous manipulation. Cases were reviewed for location, prior manipulation, rates of successful resection, adverse events, and endoscopic follow up to assess for residual lesions. Results Fifty-seven lesions underwent DeSCAR. Of the patients, 51 % were female, and average patient age was 69 years. Lesions were located in the cecum (n = 16), right colon (n = 27), left colon (n = 10), and rectum (n = 4). Average lesion size was 27.7 mm. Previous manipulation occurred in 54 cases (72 % biopsy, 44 % resection attempt, 18 % intralesional tattoo). The technical success rate for resection of non-lifting lesions was 98 %. There were two delayed bleeding episodes (one required endoscopic intervention) and one small perforation (managed by endoscopic hemoclip closure). Endoscopic follow up was available in 31 patients (54 %) with no residual adenoma in 28 patients (90 % of those surveilled). Conclusions Our expanded experience with DeSCAR demonstrates high safety, feasibility, and effectiveness for the endoscopic management of non-lifting or residual colonic lesions.
DrugOrchestra: Jointly predicting drug response, targets, and side effects via deep multi-task learning

Abstract Massively accumulated pharmacogenomics, chemogenomics, and side effect datasets offer an unprecedented opportunity for drug response prediction, drug target identification and drug side effect prediction. Existing computational approaches limit their scope to only one of these three tasks, inevitably overlooking the rich connection among them. Here, we propose DrugOrchestra, a deep multi-task learning framework that jointly predicts drug response, targets and side effects. DrugOrchestra leverages pre-trained molecular structure-based drug representation to bridge these three tasks. Instead of directly fine-tuning on an individual task, DrugOrchestra uses deep multi-task learning to obtain a phenotype-based drug representation by simultaneously fine-tuning on drug response, target and side effect prediction. By coupling these three tasks together, DrugOrchestra is able to make predictions for unseen drugs by only knowing their molecular structures. We constructed a heterogeneous drug discovery dataset of over 21k drugs by integrating 8 datasets across three tasks. Our method obtained significant improvement in comparison to methods that were trained on a single task or a single dataset. We further revealed the transferability across 8 datasets and 3 tasks, providing novel insights for understanding drug mechanisms. Availability https://github.com/jiangdada1221/DrugOrchestra
The Global Asset Management Industry: Competitive Structure and Performance

The asset management industry represents one of the most dynamic parts of the global financial services sector. Funds under institutional management are massive and growing rapidly, particularly as part of the resolution of pension pressures in various parts of the world. The industry is not, however, well understood from the perspective of industrial organization and international competition, which is the focus of this paper. It begins with a schematic of asset management in a national and global flow-of-funds context, identifying the types of asset-management functions that are performed and how they are linked into the financial system. It then assesses in some detail the three principal sectors of the asset management industry—mutual funds, pension funds, and private-client assets, as well as foundations, endowments, central bank reserves and other large financial pools requiring institutional asset management services. Relevant comparisons are drawn between the United States, Europe, Japan and selected emerging-market countries. This is followed by a discussion of the competitive structure, conduct and performance of the asset management industry, and its impact on global capital markets.
Hardship Among Immigrants and the Native-born in the United States.

This study examines the prevalence of several types of hardship (e.g., bill paying and housing hardships) among immigrants by race and ethnicity in the United States using data from the 2008 and 2014 panels of the Survey of Income and Program Participation and logistic regressions. I find that Blacks, and to some extent Hispanics, are more likely to report hardships than Whites and Asians, who are about equally likely to report hardships. Exploring results by nativity and citizenship status, I find that immigrants who became U.S. citizens are less likely than the native-born population to report some kinds of hardship. Undocumented immigrants, however, are more likely to report some kinds of hardships, particularly in the 2008 panel conducted at the time of the Great Recession, which hit immigrants especially hard; this relationship, however, is explained by the lower incomes of undocumented immigrant households in the 2008 panel. Results within racial and ethnic groups are generally in the same direction but are less frequently statistically significant. Overall, these findings suggest that immigrants are not particularly prone to hardship, especially when other characteristics are controlled for. In fact, the lower likelihood of some hardships among foreign-born citizens suggests that they are positively selected: they may have unobserved characteristics that are protective, such as better health, stronger social networks, or money management skills. Because the foreign-born are less likely to be disadvantaged vis-a-vis the native-born when hardship rather than the official income poverty measure is used, this study highlights the importance of using multiple measures when assessing the well-being of immigrants.
Ecospirituality: Vegetal Ghosts in Antoine Volodine’s Le Nom des singes (1994)

Antoine Volodine’s idiosyncratic “post-exotic” fiction has been remarked for its singular cyclical temporality and its post-apocalyptical aesthetics. In this essay, I explore the ecocritical implic...
The Implications of Hyperoxia, Type 1 Diabetes and Sex on Cardiovascular Physiology in Mice

Oxygen supplementation, although a cornerstone of emergency and cardiovascular medicine, often results in hyperoxia, a condition characterized by excessive tissue oxygen which results in adverse cardiac remodeling and subsequent injurious effects to physiological function. Cardiac remodeling is further influenced by various risk factors, including pre-existing conditions and sex. Thus, the purpose of this experiment was to investigate cardiac remodeling in Type I Diabetic (Akita) mice subjected to hyperoxic treatment. Overall, we demonstrated that Akita mice experience distinct challenges from wild type (WT) mice. Specifically, Akita males at both normoxia and hyperoxia showed significant decreases in body and heart weights, prolonged PR, QRS, and QTc intervals, and reduced %EF and %FS at normoxia compared to WT controls. Moreover, Akita males largely resemble female mice (both WT and Akita) with regards to the parameters studied. Finally, statistical analysis revealed hyperoxia to have the greatest influence on cardiac pathophysiology, followed by sex, and finally genotype. Taken together, our data suggest that Type I diabetic patients may have distinct cardiac pathophysiology under hyperoxia compared to uncomplicated patients, with males being at high risk. These findings can be used to enhance provision of care in ICU patients with Type I diabetes as a comorbid condition.
NIH Tobacco Research and the Emergence of Tobacco Regulatory Science.

Introduction This study explores how the emergence of FDA-funded Tobacco Regulatory Science (TRS) research complements and perhaps influenced the direction of tobacco research supported by NIH. Methods New NIH- and FDA-funded tobacco projects awarded in fiscal years (FY) 2011-2020 were identified using internal NIH databases of awarded grants. Project abstracts and research aims were coded by the authors to characterize research domains and tobacco products studied. Results Between FY 2011 and 2020, NIH funded 1032 and FDA funded 322 new tobacco projects. For the years and grant activity codes studied, the number of new NIH tobacco projects declined while FDA's increased; combined the number of new projects held steady. Much of NIH research included smoking combustibles (43.7%). The most common products in FDA research were cigarettes (74.8%) and e-cigarettes/ENDS (48.1%). Most NIH (58.6%) and FDA (67.7%) projects included research on the determinants of tobacco use. Another area of apparent overlap was health effects (29.5% NIH and 30.1% FDA). Projects unique to NIH included treatment interventions (33.3%), disease pathology/progression (17.8%) and neurobiology (18.9%). A minority of both NIH and FDA projects included populations particularly vulnerable to tobacco product use. Conclusions In total, support for new tobacco research supported by NIH and FDA combined remained steady for the time period covered, though there was a concomitant decline in NIH tobacco projects with the increase in FDA-funded TRS projects for the activity codes studied. Despite apparent overlap in some areas, both NIH and FDA support research that is unique to their respective missions. Implications NIH continues to support tobacco research that falls within and outside of FDA's regulatory authorities. This research still is needed not only to bolster the evidence base for regulatory decisions at the national and state levels, but also to advance a comprehensive scientific agenda that can inform multiple levels of influence on tobacco control, use and addiction. It will be important to continue monitoring FDA-funded TRS and NIH-funded tobacco research portfolios to ensure that the level of support for and focus of the research is sufficient to address the burden of tobacco-related morbidity and mortality.
Calculation of approximate variances for wage decomposition differentials

The delta method is used to estimate asymptotic variances for components of Oaxaca/Blinder style wage decompositions obtained from the semi-log regression models. Application of the method is illustrated with estimates of racial discrimination from the March 1988 CPS. Although developed in the context of estimating labor market discrimination, the variance and standard error formulas readily generalize to other contexts that use decomposition methods.
Professionalism, self-regulation, and motivation: how did health care get this so wrong?

societies in the medical profession’s long-standing tradition of self-regulation, and what actions and influences might enhance the ability of the medical profession to operate effectively and responsibly? Such questions seem natural given the rapidly changing health care system with the emergence of a plethora of new payment and delivery models—all hoping to achieve the Institute for Healthcare Improvement’s Triple Aim initiative for better health, better health care, and lower cost. It is critical that the medical profession demonstrate its ability to respond to these changing environments in ways that both acknowledge and advance society’s interest in having an optimal physician workforce. It is equally critical to understand factors that underpin the noblest traits in physicians then deploy this knowledge in shaping delivery systems that emerge. Self-regulation is a central tenet of professions, has been long-standing, and has seen multiple professions through vast environmental change. Indeed, the professions of medicine, divinity, and law have been
Design and Testing of Electrical Insulation for Superconducting Coils

This paper reviews and summarizes the dielectric properties of liquid and gaseous helium and nitrogen, vacuum, and solid insulation materials for practical insulation design for superconducting coils. The influence of electrode geometry on breakdown voltage is discussed, and features that require special care are pointed out. Appropriate room-temperature high-voltage testing is considered. Finally, the paper examines the implications for coil insulation design of a new class of superconductors that can operate at temperatures approaching 77 K.
The Unifying Moral Dyad Liberals and Conservatives Share the Same Harm-Based Moral Template

Do moral disagreements regarding specific issues (e.g., patriotism, chastity) reflect deep cognitive differences (i.e., distinct cognitive mechanisms) between liberals and conservatives? Dyadic morality suggests that the answer is "no." Despite moral diversity, we reveal that moral cognition--in both liberals and conservatives--is rooted in a harm-based template. A dyadic template suggests that harm should be central within moral cognition, an idea tested--and confirmed--through six specific hypotheses. Studies suggest that moral judgment occurs via dyadic comparison, in which counter-normative acts are compared with a prototype of harm. Dyadic comparison explains why harm is the most accessible and important of moral content, why harm organizes--and overlaps with--diverse moral content, and why harm best translates across moral content. Dyadic morality suggests that various moral content (e.g., loyalty, purity) are varieties of perceived harm and that past research has substantially exaggerated moral differences between liberals and conservatives.
Retrieval of Physical and Optical Cloud Thicknesses from Space-Borne and Wide-Angle Imaging Lidar

Pulsed laser beams are essentially δ-functions in space, time and direction; lidar returns are therefore the remotely observable parts of the cloud’s Green function for radiative transfer. However, “observable” is not limited here a priori to quasi-backscattered radiance, so propagation away from the laser beam and back to the detector by multiple scattering through arbitrarily large angles is considered. We present heuristic arguments demonstrating that the primary information conveyed by Green functions in the spatial/angular and time domains can, in principle, be combined to retrieve the physical and optical thicknesses of stratiform clouds at about 0.5 km resolution. The photon random walk theory presented here is justified by in-cloud “diffusion domain” observations and validated by statistical analyses of real and simulated LANDSAT radiance fields, as well as a remarkable result from LITE. The remaining challenge is to detect the weak, highly-scattered signal. Strategies for ground- and space-borne designs are discussed in the framework of current lidar and low-light imaging technologies.
CELLULAR AND MOLECULAR BIOLOGY OF OPTINEURIN

Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other neurodegenerative diseases, and Paget's disease of bone. This review describes the characteristics of optineurin and summarizes the cellular and molecular biology investigations conducted so far on optineurin. Data from a number of laboratories indicate that optineurin is a cytosolic protein containing 577 amino acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin, transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NF-κB pathway, antiviral, and antibacteria signaling. Mutation or alteration of homeostasis of optineurin (such as overexpression or knockdown) results in adverse consequences in the cells, leading to the development of neurodegenerative diseases including glaucoma.
[18F]Fallypride: Metabolism studies and quantification of the radiotracer and its radiometabolites in plasma using a simple and rapid solid-phase extraction method

Abstract Introduction [ 18 F]Fallypride, a fluorinated and substituted benzamide with high affinity for D 2 /D 3 receptors, is a useful PET radioligand for the study of striatal/extrastriatal areas. Since [ 18 F]fallypride is extensively metabolized in vivo and since PET examinations are long lasting in humans, the rapid measurement of the unchanged radiotracer in plasma is essential for the quantification of images. The present study aims: i) to evaluate if the radiometabolites of [ 18 F]fallypride cross the blood–brain barrier in rodents, ii) to identify these radiometabolites in baboon plasma and iii) to develop a rapid solid phase extraction method (SPE) suitable for human applications to quantify both [ 18 F]fallypride and its radiometabolites in plasma. Methods The metabolites P450-dependant in rat and human liver microsomes were characterized by LC–MS–MS and compared to those detected in vivo . Sequential solvent elution on Oasis®-MCX-SPE cartridges was used to quantify [ 18 F]fallypride and its radiometabolites. Result In rat microsomal incubations, five metabolites generated upon N/O -dealkylation or hydroxylation at the pyrrolidine and/or at the benzamide moiety were identified. No radiometabolite was detected in the rat brain. N -dealkylated and hydroxylated derivatives were detected in human microsomal incubations as well as in baboon plasma. The use of SPE (total recovery 100.2% ± 2.8%, extraction yield 95.5% ± 0.3%) allowed a complete separation of [ 18 F]fallypride from its radiometabolites in plasma and evaluate [ 18 F]fallypride at 150 min pi to be 22% ± 5% of plasma radioactivity. Conclusions The major in vivo radiometabolites of [ 18 F]fallypride were produced by N -dealkylation and hydroxylation. Allowing the rapid analysis of multiple plasma samples, SPE is a method of choice for the determination of [ 18 F]fallypride until late images required for quantitative PET imaging in humans.
Finite element modeling of a microelectronic structure under uniform thermal loading

The deformation and thermal stresses that develop in copper/polyimide high-density interconnects subjected to thermal loading are investigated numerically. The finite element method is used to analyze the response of a single-level test structure composed of a thin film mounted on top of a silicon substrate. The structure is assumed to be stress-free at an elevated temperature, and is then cooled at various rates. Based on the experimental observations we allow for diffusionally accommodated sliding at the copper/tantalum interfaces by assuming a linear relationship between the shear traction and the conjugate sliding rate. The effects of interfacial roughness and cooling rate on the overall mechanical response of the structure are investigated and the results are discussed.
Aggregation and territoriality of Cuterebra lepivora (Diptera:Cuterebridae).

Two aggregations of male Cuterebra lepivora were discovered in an open area of brush and dry grasses in Poso Creek basin, Kern Co., California, USA. Males established and defended territories against conspecific males and responded to females that entered their territories. The density of territorial males did not exceed 4 individuals per aggregation. Males exhibited temporal changes in perching behavior within defended territories. Two couplings between males and females occurred above the aggregations.
Fluorescent fiber-optic sensor arrays probed utilizing evanescent fiber-fiber coupling

Optical-fiber sensors that use fluorescent probes located in the fiber cladding are of great interest for monitoring physical and chemical properties in their environment. The interrogation of a fluorophore with a short laser pulse propagating through the fiber core allows for the measurement of the location of the fluorophore by measuring the time delay between the exciting pulse and the returning fluorescence pulse. The spatial resolution of such an array of fluorescent sensors is limited since a minimum separation of the fluorophores is required to resolve returning light pulses. For many applications a closer spacing of sensor regions is desirable, particularly for fibers prepared by using our recently introduced one-dimensional combinatorial chemistry method [A. W. Schwabacher et al., J. Am. Chem. Soc. 121, 8669 (1999)]. This method allows for efficient preparation of large, diverse, and densely packed linear arrays of sensors. We demonstrate that by using a second fiber as an optical delay line, the minimum spacing between adjacent sensor regions can be well below the fluorescence lifetime limit. Since the coupling between the two fibers is evanescent, the attenuation of the excitation pulse is low, making long arrays of sensor regions feasible. Moreover, we identify the conditions that allow for the optical readout of long arrays of sensors.
Electrospun nitrocellulose and nylon: Design and fabrication of novel high performance platforms for protein blotting applications

Electrospinning is a non-mechanical processing strategy that can be used to process a variety of native and synthetic polymers into highly porous materials composed of nano-scale to micron-scale diameter fibers. By nature, electrospun materials exhibit an extensive surface area and highly interconnected pore spaces. In this study we adopted a biological engineering approach to ask how the specific unique advantages of the electrospinning process might be exploited to produce a new class of research/diagnostic tools. The electrospinning properties of nitrocellulose, charged nylon and blends of these materials are characterized. Nitrocellulose electrospun from a starting concentration of < 110 mg/ml acetone deposited as 4–8 μm diameter beads; at 110 mg/ml-to-140 mg/ml starting concentrations, this polymer deposited as 100–4000 nm diameter fibers. Nylon formed fibers when electrospun from 60–140 mg/ml HFIP, fibers ranged from 120 nm-6000 nm in diameter. Electrospun nitrocellulose exhibited superior protein retention and increased sensitivity in slot blot experiments with respect to the parent nitrocellulose material. Western immunoblot experiments using fibronectin as a model protein demonstrated that electrospun nylon exhibits increased protein binding and increased dynamic range in the chemiluminescence detection of antigens than sheets of the parent starting material. Composites of electrospun nitrocellulose and electrospun nylon exhibit high protein binding activity and provide increased sensitivity for the immuno-detection of antigens. The flexibility afforded by electrospinning process makes it possible to tailor blotting membranes to specific applications. Electrospinning has a variety of potential applications in the clinical diagnostic field of use.
Actualistic models of mantle metasomatism documented in a composite xenolith from Dish Hill, California

Major and trace-element whole rock and mineral variations in composite hornblendite-peridotite xenolith Ba-2-1, from Dish Hill, CA, are due to a single event of metasomatism in the mantle. The hornblendite is the crystallized selvage of a dike conduit charged with incompatible-element-enriched hydrous mafic magma. The magma infiltrated the refractory peridotite wallrock, reacted with its constituent minerals, and simultaneously deposited amphibole. The systematic data from this study show considerable variation in isotopic values and trace elements. These data provide insight into a mantle process that was defined previously from samples without context, lacking evidence about the number or source of metasomatic events. In the contact zone of Ba-2-1, peridotite is enriched in Fe, Ti, CO2) and H2O; clinopyroxene and amphibole also are enriched in Fe and Ti, but clinopyroxene appears slightly depleted in CaO. Compared to chondrites, peridotite, clinopyroxene, and probably amphibole are enriched in light rare earth (LREEcn) and other incompatible trace elements. Values of 87Sr86Sr and 143Nd144Nd in the contact zone are close to isotopic equilibrium with the dike. Whole rock and constituent clinopyroxene compositions change to those of refractory peridotite with distance from the contact. These compositional variations were modelled using Gresens' equation for whole-rock major and minor elements, and calculations for isotopic ratios and REEs, which emulate the effects of Chromatographic fractionation. The choice of endmembers was restricted to compositions actually present in mantle samples from Dish Hill. Model results indicate that: 1. (1) the variations can be explained as the result of a single metasomatic event, probably a single pulse of previously fractionated liquid; 2. (2) the ratio of total interacting liquid to peridotite was at least 1:3 by weight in the contact zone; and 3. (3) the composition of the metasomatic liquid changed progressively as it infiltrated beyond that zone. The small distance over which variations occur is due to the small amount of liquid that infiltrated. Only in the contact zone was peridotite wallrock saturated by a liquid composition similar to the dike. Comparison of the Ba-2-1 data with those of another xenolith from Dish Hill suggests that the compositional variations of mantle metasomatism result from both the compositional contrast between the metasomatizing liquid and wallrock and the relative abundances of each. Compositional and volumetric variations of mantle partial melts and their fractionates, and repeated events of melting and reaction in contiguous mantle, can create broad ranges of metasomatic “signatures” from the same process.
Carbon cycle: sources, sinks and seasons.

Changes in the phasing of seasonal cycles of carbon dioxide in the atmosphere mark the time when a region becomes a source or a sink of CO2. One study of such changes prompts thought-provoking conclusions. An analysis of variations in atmospheric CO2 and ecosystem CO2 fluxes in the Northern Hemisphere shows that warmer autumns have been associated with an earlier autumn-to-winter CO2 build-up in the atmosphere. This seems counter-intuitive: warm autumns surely imply long growing seasons and a beneficial effect on terrestrial carbon sinks as trees and plants make more biomass. An explanation is provided by satellite observations and numerical modelling. Enhanced respiration caused by higher temperatures causes carbon losses that offset photosynthetic gains, limiting the potential of these ecosystems to act as carbon sinks. And CO2 loss due to autumn warming may offset most of the increased CO2 uptake during spring. If future warming occurs more rapidly in autumn than in spring, the ability of northern ecosystems to sequester carbon may diminish more rapidly than previously predicted.