cssi/SciSciGPT-SciSciNet huggingface dataset:
Relationship of the 20S proteasome and the proteasome activator PA28 to atherosclerosis and intimal hyperplasia in the human vascular system.

Down-regulation of the proteasome activator PA28 results in abnormal proteasome activation and has been implicated in the development of intimal hyperplasia (IH) in animal models. Demonstration of proteasome and PA28 expression has not yet been documented in the human vascular system. This study sought to define the distribution of the 20S proteasome and its activator PA28 in human vessels and determine the relationship between the expression of the proteasome and PA28 and the development of atherosclerosis and IH. Vascular biopsies were obtained from 70 patients at the time of surgery, were snap frozen and sectioned in 5-μm sections, and prepared using standard histological techniques. The immunoperoxidase technique was used to identify 20S proteasome and PA28 expression in diseased and normal human arteries and veins as well as in patent bypass grafts with and without IH. Expression was graded by a blinded pathologist (scale: 1–4). Repeat quantification of the immunopositive cells was also performed. Expression of 20S proteasome and PA28 was identified in all vascular tissues examined. The proteins were identified predominately within the cytoplasm of vascular smooth muscle cells and endothelial cells. PA28 was more intensely expressed in quiescent regions of the vessel wall as compared to areas undergoing active proliferation and remodeling. PA28-mediated activation of the proteasome may be necessary to maintain normal cellular homeostasis and prevent excessive cellular proliferation in the human vascular system. Abnormalities of proteasome activation may have a significant role in the development of atherosclerosis and IH.
High resolution subsurface microscopy technique

The numerical aperture increasing lens (NAIL) technique increases the NA and subsequent resolution while preserving stigmatic imaging, and is therefore a significant improvement over standard optical microscopy for subsurface imaging at the diffraction limit. We give experimental data which demonstrates the NAIL technique capability.
Cost-Utility Analyses in Orthopaedic Surgery

Background: The rising cost of health care has increased the need for the orthopaedic community to understand and apply economic evaluations. We critically reviewed the literature on orthopaedic cost-utility analysis to determine which subspecialty areas are represented, the cost-utility ratios that have been utilized, and the quality of the present literature. Methods: We searched the English-language medical literature published between 1976 and 2001 for orthopaedicrelated cost-utility analyses in which outcomes were reported as cost per quality-adjusted life year. Two trained reviewers independently audited each article to abstract data on the methods and reporting practices used in the study as well as the cost-utility ratios derived by the analysis. Results: Our search yielded thirty-seven studies, in which 116 cost-utility ratios were presented. Eleven of the studies were investigations of treatment strategies in total joint arthroplasty. Study methods varied substantially, with only five studies (14%) including four key criteria recommended by the United States Panel on Cost-Effectiveness in Health and Medicine. According to a reader-assigned measure of study quality, cost-utility analyses in orthopaedics were of lower quality than those in other areas of medicine (p = 0.04). While the number of orthopaedic studies has increased in the last decade, the quality did not improve over time and did not differ according to subspecialty area or journal type. For the majority of the interventions that were studied, the cost-utility ratio was below the commonly used threshold of $50,000 per quality-adjusted life year for acceptable cost-effectiveness.
The Representation of Illusory and Real Contours in Human Cortical Visual Areas Revealed by Functional Magnetic Resonance Imaging

Illusory contours (perceived edges that exist in the absence of local stimulus borders) demonstrate that perception is an active process, creating features not present in the light patterns striking the retina. Illusory contours are thought to be processed using mechanisms that partially overlap with those of “real” contours, but questions about the neural substrate of these percepts remain. Here, we employed functional magnetic resonance imaging to obtain physiological signals from human visual cortex while subjects viewed different types of contours, both real and illusory. We sampled these signals independently from nine visual areas, each defined by retinotopic or other independent criteria. Using both within- and across-subject analysis, we found evidence for overlapping sites of processing; most areas responded to most types of contours. However, there were distinctive differences in the strength of activity across areas and contour types. Two types of illusory contours differed in the strength of activation of the retinotopic areas, but both types activated crudely retinotopic visual areas, including V3A, V4v, V7, and V8, bilaterally. The extent of activation was largely invariant across a range of stimulus sizes that produce illusory contours perceptually, but it was related to the spatial frequency of displaced-grating stimuli. Finally, there was a striking similarity in the pattern of results for the illusory contourdefined shape and a similar shape defined by stereoscopic depth. These and other results suggest a role in surface perception for this lateral occipital region that includes V3A, V4v, V7, and V8.
Tensile Behavior of a Quasi‐Isotropic Carbon‐Carbon Composite

This paper reports an analytical and experimental investigation of the tensile behavior of a two-dimensional woven carbon-carbon composite with a quasi-isotropic stacking sequence. Specimens in their as-received condition were already saturated with transverse cracks due to thermal stress induced during fabrication. Further cracking under load was not detected. The completely unloaded specimen showed that the slight residual strain tended to increase with applied tensile strain. Damage progression as seen on specimen edges and elastic moduli degradation were recorded. The predicted Young's moduli were in good agreement with the measured data.
Bite force is limited by the force-length relationship of skeletal muscle in black carp, Mylopharyngodon piceus

Bite force is critical to feeding success, especially in animals that crush strong, brittle foods. Maximum bite force is typically measured as one value per individual, but the force–length relationship of skeletal muscle suggests that each individual should possess a range of gape height-specific, and, therefore, prey size-specific, bite forces. We characterized the influence of prey size on pharyngeal jaw bite force in the snail-eating black carp (Mylopharyngodon piceus, family Cyprinidae), using feeding trials on artificial prey that varied independently in size and strength. We then measured jawclosing muscle lengths in vivo for each prey size, and then determined the force–length relationship of the same muscle in situ using tetanic stimulations. Maximum bite force was surprisingly high: the largest individual produced nearly 700 N at optimal muscle length. Bite force decreased on large and small prey, which elicited long and short muscle lengths, respectively, demonstrating that the force–length relationship of skeletal muscle results in prey size-specific bite force.
Flavor unification and discrete non-Abelian symmetries.

Grand unified theories with fermions transforming as irreducible representations of a discrete non-Abelian flavor symmetry can lead to realistic fermion masses, without requiring small fundamental parameters. We construct a specific example of a supersymmetric GUT based on the flavor symmetry \ensuremath{\Delta}(75), a subgroup of SU(3), which can explain the observed quark and lepton masses and mixing angles. The model predicts tan\ensuremath{\beta}\ensuremath{\simeq}1 and gives a \ensuremath{\tau} neutrino mass ${\mathit{m}}_{\ensuremath{\nu}}$\ensuremath{\simeq}${\mathit{M}}_{\mathit{p}}$/${\mathit{G}}_{\mathit{F}}$${\mathit{M}}_{\mathrm{GUT}}^{2}$=10 eV, with other neutrino masses much lighter. Combined constraints of light quark masses and perturbative unification place flavor symmetry-breaking near the GUT scale; it may be possible to probe these extremely high energies by continuing the search for flavor-changing neutral currents.
ASSESSMENT OF CURRENT DIAGNOSTIC CRITERIA FOR GUILLAIN-BARRE SYNDROME

Criteria for the diagnosis of Guillain-Barre syndrome are reaffirmed. Electrodiagnostic criteria are expanded and specific detail added.
Rare solitary benign tumors of the lung

Abstract Benign solitary neoplasms of the lung are relatively uncommon but nonetheless must be considered in the differential diagnosis of any solitary pulmonary lesion. Ironically, the advent of improved tomographic imaging and its increasingly broad clinical application have led to a greater recognition of benign solitary pulmonary lesions, presenting the surgeon with a complex management dilemma. Most benign lesions are relatively bland radiographically, making their differentiation from carcinoma difficult. Often, diagnostic certainty can only be achieved with complete resection. Fortunately, advances in minimally invasive thoracic surgery make this prospect less daunting for the patient and surgeon. This article reviews a subset of solitary lesions categorized as rare benign neoplasms from histologic, radiographic, and clinical points of view. © 2003 Elsevier Inc. All rights reserved.
Oral Healthcare and Health Disparities for Women: A Brief Report

Poor dental health increases the risk for a myriad of systemic diseases and poor health outcomes including diabetes, and heart disease. Associations have been documented between periodontal disease diabetes, cardiovascular disease, and gastrointestinal disorders. Additionally, poor oral health has been associated with premature birth, and poor birth outcomes. Poor birth outcomes can stem from the influx of infant mortality across the US; thus significantly impacting the overall health of women. Women who come from low social economic areas, underserved populations, and underrepresented groups should be provided the necessary access to oral health care to assist with overall systemic health of women and prevent health problems such as heart disease, diabetes, premature birth, and poor birth outcomes. Overall, as a healthcare profession we must come together for the betterment of women’s health and advocate overall systemic health including oral health.
Severity of bipolar disorder is associated with impairment of response inhibition

Abstract Background: Pathological impulsivity in bipolar disorder could be related to deficiencies in mechanisms involved in attention or response inhibition. We investigated these mechanisms in subjects with bipolar disorder and examined relationships to severity of course of illness, use of medication, affective state, age, education, and gender. We measured two complementary aspects of response inhibition: attention-based and reward-based. Methods: Subjects with bipolar disorder (n = 112) and healthy controls (n = 71) were recruited from the community. Diagnoses were rendered using the SCID for DSMIV. Impulsivity-related measures included the Immediate Memory Task (IMT), a form of the Continuous Performance Task, and the Single Key Impulsivity Paradigm (SKIP), an operant procedure measuring ability to delay responding for a reward. Results: Subjects with bipolar disorder had fewer correct detections (Effect Size (ES) = 0.5), prolonged reaction times (ES = 0.88), and decreased discriminability (ES = 0.57) on the IMT compared to controls. History of frequent episodes, substance use disorders, or suicide attempts predicted faster reaction times, especially to a commission error. Subjects with bipolar disorder who also met criteria for an Axis II disorder had fewer correct detections, more commission errors relative to correct detections, and poorer discriminability on the IMT than other subjects with bipolar disorder. Subjects with bipolar disorder made more responses on the SKIP than did controls (ES = 0.5), with a shorter maximum delay (ES = 0.62), consistent with inability to delay reward. Probit analysis showed that faster reaction time to a commission error on the IMT was associated with history of substance use disorder, suicide attempt, or many previous episodes. Effects of medication or affective state did not account for these differences. Discussion: Bipolar disorder was associated with impairment in attention and response inhibition, encompassing impaired inhibition of rapid responses and an inability to delay reward, and resulting in impulsivity. Response inhibition mechanisms are impaired further in subjects with more severe complications of illness.
A Performance-inspired Building Representation for Computational Design

A building representation for integrated building performance simulation is described, which addresses several important issues. First, it captures informational requirements for detailed performance analysis and maintains geometric integrity. Second, it provides computational support for efficient spatial queries and convenient building model manipulation. Representational elements include partitioning and refinement rules, containment hierarchies and dimension constraints. These features provide for ease of manipulation, geometric variety and spatial queries and are illustrated with examples. The paper concludes with a discussion of the limitations of the representation.
The Axiom of Extension

A pack of wolves, a bunch of grapes, or a flock of pigeons are all examples of sets of things. The mathematical concept of a set can be used as the foundation for all known mathematics. The purpose of this little book is to develop the basic properties of sets. Incidentally, to avoid terminological monotony, we shall sometimes say collection instead of set. The word “class” is also used in this context, but there is a slight danger in doing so. The reason is that in some approaches to set theory “class” has a special technical meaning. We shall have occasion to refer to this again a little later.
L’ «Histoire naturelle» dans le Roman d’Enéas: Cinq notes sur Pline et les merveilles au XIIe siècle

This brief and somewhat anecdotal note analyzes five instances drawn from the Roman d’Eneas (a high medieval adaptation of Virgil’s Aeneid) in relation to descriptions in Historia naturalis of Pliny the Elder. The examples illustrate the twelfth-century anonymous romancer’s exploitation of: murex, the marvelous horses of Messapus, bitumen, chalcedony and scammony.
Anterior Urethral Injuries: Four Years of Experience at the Detroit General Hospital

Among 19 patients with trauma of the anterior urethra 16 were treated by urinary diversion without primary repair of the injured area. Of these patients 15 recovered with excellent results. Since most traumatic injuries to the anterior urethra are partial disruptions we believe that urinary diversion may be the only treatment needed.
Using the Parallel Offset Function to Achieve Required Delay

In time-based flow management the ability to control spacing of adjacent aircraft and to meet required time at a metering point is essential for efficient high density traffic flows. Meeting these conditions when flying an idle thrust continuous descent approach presents a challenge to expanding the use of this ecologically preferred descent procedure. In this paper we present the use of the parallel offset (also called “lateral offset”) as a means of effectively meeting a time of arrival constraint. Calculations demonstrate that the offset can effectively fine-tune arrivals times with little interaction with nearby traffic.
Reactivity of organothorium complexes with TEMPO.

Reactions of the 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO) with thorium metallocenes have been examined to investigate both the radical reaction patterns for organothorium complexes and the coordination chemistry of TEMPO with thorium. (η5-C5Me5)2ThMe2 reacts with 2 equiv of TEMPO to generate 1-methoxy-2,2,6,6-tetramethylpiperidine (Me-TEMPO) and (η5-C5Me5)2ThMe(η1-TEMPO), which contains a TEMPO– anion coordinated to thorium through oxygen only. (η5-C5Me5)2Th(η1-C3H5)(η3-C3H5), synthesized from (η5-C5Me5)2ThBr2 and (C3H5)MgBr, reacts with 2 equiv of TEMPO to form 1-(2-propen-1-yloxy)-2,2,6,6-tetramethylpiperidine (allyl-TEMPO) and (η5-C5Me5)2Th(η1-C3H5)(η1-TEMPO). Although bis(TEMPO) metallocenes were not obtained in these reactions, the methyl group in (η5-C5Me5)2ThMe(η1-TEMPO) is reactive with 1 equiv of CuBr to form (η5-C5Me5)2ThBr(η1-TEMPO). The bis(TEMPO) metallocene (η5-C5Me5)2Th(η1-TEMPO)2 is accessible in the reaction of [(η5-C5Me5)2ThH2]2 with 4 equiv of TEMPO. In contrast, (η5-C5Me5)2T...
Luminous Subjects Photographed with Auxiliary Light

The electronic flash, strobe, or spark light sources have great ability to take photographs with short exposure. The peak light intensity must, of necessity, be very high to create an exposure in a short time.
Frustrated magnetism in the spin–chain metal Yb2Fe12P7

Magnetization measurements for magnetic fields up to 60 T are reported for the noncentrosymmetric spin–chain metal Yb2Fe12P7. These measurements reveal behavior that is consistent with Ising-like spin chain magnetism that produces pronounced spin degeneracy. In particular, we find that although a Brillouin field dependence is observed in M(H) for with a saturation moment that is close to the expected value for free ions of Yb3+ , non-Brillouin-like behavior is seen for with an initial saturation moment that is nearly half the free ion value. In addition, hysteretic behavior that extends above the ordering temperature is seen for but not for , suggesting out-of-equilibrium physics. This point of view is strengthened by the observation of a spin reconfiguration in the ordered state for which is only seen for and after polarizing the spins. Together with the heat capacity data, these results suggest that the anomalous low temperature phenomena that were previously reported (Baumbach 2010 et al Phys. Rev. Lett. 105 106403) are driven by spin degeneracy that is related to the Ising-like one dimensional chain-like configuration of the Yb ions.
Improving network performance on multicore systems

Network throughput is scaling-up to higher data rates while end-system processors are scaling-out to multiple cores. In order to optimize high speed data transfer into multicore end-systems, techniques such as network adaptor offloads and performance tuning have received a great deal of attention. Furthermore, several methods of multi-threading the network receive process have been proposed. However, thus far attention has been focused on how to set the tuning parameters and which offloads to select for higher performance, and little has been done to understand why the various parameter settings do (or do not) work. In this paper, we build on previous research to track down the sources of the end-system bottleneck for high-speed TCP flows. We define protocol processing efficiency to be the amount of system resources (such as CPU and cache) used per unit of achieved throughput (in Gbps). The amount of various system resources consumed are measured using low-level system event counters. In a multicore end-system, affinitization, or core binding, is the decision regarding how the various tasks of network receive process including interrupt, network, and application processing are assigned to the different processor cores. We conclude that affinitization has a significant impact on protocol processing efficiency, and that the performance bottleneck of the network receive process changes significantly with different affinitization. Affinity, or core binding, maps processes to cores in a multicore system.We characterized the effect of different receiving flow and application affinities.We used OProfile as an introspection tool to examine software bottlenecks.The location of the end-system bottleneck was dependent on the choice of affinity.There are multiple sources of end-system bottlenecks on commodity hardware.
Measuring time utilization of pharmacists in the Birmingham Free Clinic dispensary

Free and charitable clinics are a critical part of America’s healthcare safety net. Although informatics tools have the potential to mitigate many of the organizational and service-related challenges facing these clinics, little research attention has been paid to the workflows and potential impact of electronic systems in these settings. In previous work, we performed a qualitative investigation at a free clinic dispensary to identify workflow challenges that may be alleviated through introduction of informatics interventions. However, this earlier study did not quantify the magnitude of these challenges. Time-motion studies offer a precise standard in quantifying healthcare workers’ time expenditures on clinical activities, and can provide valuable insight into system specifications. These data, informed by a lean healthcare perspective, provide a quality improvement framework intended to maximize value and eliminate waste in inefficient workflow processes. We performed a continuous observation time-motion study in the Birmingham Free Clinic dispensary. Two researchers followed pharmacists over the course of three general clinic sessions and recorded the duration of specific tasks. Pharmacists were then asked to identify tasks as value-added or non-value-added to facilitate calculation of the value quotient, a metric used to determine a workflow’s level of efficiency. Four high-level workflow categories occupied almost 95 % of pharmacist time: prescription (Rx) preparation (39.8 %), clinician interaction (21.5 %), EMR operations (14.8 %), and patient interaction (18.7 %). Pharmacists invested the largest portion of time in prescription preparation, with 21.8 % of pharmacist time spent handwriting medication labels. Based on value categorizations made by the pharmacists, the average value quotient was found to be 40.3 %, indicating that pharmacists spend more than half of their time completing tasks they consider to be non-value-added. Our results show that pharmacists spend a large portion of their time preparing prescriptions, primarily the handwritten labeling of medication bottles and documentation tasks, which is not an optimal utilization of pharmacist expertise. The value quotient further supports that there are many wasteful tasks that may benefit from workflow redesign and health information technology, which could result in efficiency improvements for pharmacists.
Notes on reproduction of Jackson's chameleon Chamaeleo jacksonii (Squamata, Chamaeleonidae), from Hawaii

Histological examination of gonads from invasive Chamaeleo jacksonii collected in oahu, Hawaii revealed both male and female populations were reproductively active in December and February. Litter sizes of 12.2 ± 4.4 sD (range 7-21) are within limits reported for C. jacksonii in previous studies. Linear regression analysis revealed a significant positive relationship between C. jacksonii female body size and clutch size. The smallest reproductively mature females measured 94 mm sVL. adult males were significantly larger than females. The smallest reproductively mature C. jacksonii male from Hawaii measured 70 mm sVL as opposed to 90 mm in kenya (Lin & Nelson, 1981). This indicates Hawaiian C. jacksonii males join the breeding population at an earlier age compared to those in native populations and this may suggest that C. jacksonii has a higher reproductive potential in Hawaii compared with kenya.
Mapping of Allosteric Modulator Effects in the Active Site of Factor IXa.

Abstract Activated factor IX (fIXa) is a vitamin K-dependent blood coagulation serine protease involved in propagation of the coagulant response through activation of fX. Maximal enzymatic and procoagulant activity of fIXa requires the presence of several cofactors; one of which is ionic calcium, which is known to bind to a site in the protease domain of fIXa as well as several sites within the light chain Gla domain region. One of the roles of calcium appears to be allosteric modulation of the fIXa active site as evidenced by an increase in enzymatic activity towards small peptidyl substrates. We and others have additionally found that certain small hygroscopic molecules can also enhance fIXa amidolytic activity. The molecular details involved in either of these effects are not well understood. Previous studies by us have shown that a pentapeptide substrate (AGRSL; the reactive site sequence of antithrombin) is hydrolyzed by fIXa in the absence of cofactors or modulators. This hydrolysis is enhanced in the presence of ionic calcium, ethylene glycol or low molecular weight heparin suggesting effects of these molecules on the immediate active site vicinity of fIXa. In order to gain insight into the potential allosteric modulation that each of these effectors may affect in fIXa, we examined the hydrolysis of four peptide libraries based on the AGRSL pentapeptide sequence, in the presence and absence of various fIXa modulators. The four libraries synthesized were XGRSL, AXRSL, AGRXL and AGRSX; where X denotes any of the possible 20 amino acids. Each of these libraries were screened for hydrolysis by fIXa under various conditions with substrates and products being identified en masse using MALDI-TOF mass spectrometry. The results suggest that ionic calcium enhances fIXa reactivity in part by modulation of the S2 subsite in fIXa. In contrast, ethylene glycol enhances fIXa activity via modulation of the S3 subsite and heparin was found to effect the overall active site region.
Hydroclimatic variability and change in the Chesapeake Bay Watershed

The Chesapeake Bay (CB) Watershed is undergoing changes in climate, hydrology, and land use. The assessment of hydroclimatic impacts is important for both water quantity and quality management. This study evaluated the hydroclimatic changes using the Coupled Model Intercomparison Project 5 (CMIP5) data which provided statistically downscaled daily precipitation and temperature. An increase of 3.0 to 5.2 °C in temperature was projected between 2070 and 2099 when compared with the baseline period of 1970–1999. However, precipitation projections showed a modest increase with an average of 5.2 and 8.4% between 2070 and 2099. The northern part of the CB Watershed was expected to be wetter and warmer than the southern region. The average changes in flow were projected between −12 and 6% and −22 to 5% between 2070 and 2099, respectively, under two scenarios. Minimum changes in winter and highest flow reduction in fall with a high degree of variability among the ensemble members was expected. Greater decrease in flows in the northern region of the CB Watershed was projected. Despite the wetter future projections at the end of the century and uncertainties in our evapotranspiration (ET) estimation, reductions in the land surface runoff partly were attributed to increased ET.
Somatic mutation spectrum of non-small cell lung cancers (NSCLCs) from African Americans (AAs).

6038 Background: In the AA population, previous studies have presented conflicting data on the frequency of EGFR mutations (Reinersman JTO 2011;Leidner JCO 2009), while frequencies of other gene mu...
COST AND UTILIZATION OF DEMENTIA CARE ECOSYSTEM AND GENERAL MEDICARE DEMENTIA PATIENTS

Author(s): Wilson, L; Chen, Y; Lin, T; Laohavanich, S; Possin, K; Chiong, W; Bonasera, S; Miller, B
A computerized algorithm to capture patient’s past preeclampsia and eclampsia history from prenatal clinical notes:

Prenatal clinical notes in electronic medical records contain a wealth of information on pregnancy complications and outcomes. Extracting this critical information provides a unique opportunity for...
A twist of fate

The possibility has emerged that fusion could be a significant means by which cells might be 'reprogrammed' for a different function in adulthood.
Algorithms for Mesh Connected Computers

This chapter presents algorithms for solving a number of problems on mesh connected computers. The problems that were selected fall into the categories of basic communication operations, image processing, and scientific applications. The algorithms in this section will be for the plain mesh connected computer. A plain mesh connected computer operates in an SIMD mode. The PEs use uniform addressing in accessing their memories (all PEs access the same local memory location at any given time), and communication is weak and uniform (each PE can send a message to only one neighbor at a time, and all PEs communicate in the same direction). The PEs can be selectively disabled by using mask registers. The top and bottom rows and the leftmost and rightmost columns are connected, so that the interconnections logically form a torus. It should be noted, however, that a machine that does not have these “wraparound” connections can simulate a machine that does have them with only a constant factor increase in time. In particular, consider a P1/2 × P1/2 mesh connected computer without wraparound connections, where P½ is an even integer. Let the function f(i) be defined such that f(i) = 2i, if 0 ≤ i < P½/2, and f(i) = 2P½ − 2i − 1, if P½ ≤ i < P½. Each processor (i, j) of a P½ × P½ mesh with wraparounds is mapped to processor [f(i), f(j)] of a P½ × P½ mesh without wraparounds.
Age: Apparent Time and Real Time

A growing body of longitudinal studies allow us to examine diachronically the historical extrapolations originally made in synchronic sociolinguistic research. Apparent time and age grading are two interpretive schemata Labov originally proposed to account for regular progression in the value of a linguistic variable across an age distribution of speakers. Trend and panel studies frequently reveal a combination of these two effects. Trend studies have consistently shown that real time change in the speech community outpaces change across individual lifespans as measured by panel studies. Apparent time interpretations thus often tend not to mistakenly assume change, but to underestimate the rate of change.
Phase III Clinical Efficacy of Indacaterol: Patient-Centered Outcomes

International guidelines for the treatment of patients with chronic obstructive pulmonary disease (COPD) state that effective management should relieve symptoms, improve health status, prevent exacerbations, and improve exercise tolerance. In randomized placebo-controlled trials evaluating once-a-day indacaterol over 26–52 weeks, valid, reliable, and responsive instruments/methods were used to quantify the impact of treatment on patient outcomes. Compared with placebo treatment, both 150 and 300 μg doses of indacaterol provided significant and clinically meaningful improvements in dyspnea as measured by the Transition Dyspnea Index. Analyses showed that as-needed use of salbutamol, an indirect assessment of the efficacy of therapy on relief of dyspnea, was significantly lower with 150 and 300 μg doses of indacaterol than with placebo. With 150 and 300 μg doses of indacaterol, there were significant improvements in health status, as measured by the St. George’s Respiratory Questionnaire, relative to placebo therapy. In two of three randomized trials, the differences in the St. George’s Respiratory Questionnaire between indacaterol and placebo achieved the minimal important difference of −4 U. Time to first exacerbation was significantly decreased with 150 and 300 μg doses of indacaterol compared with placebo. In two randomized trials published as abstracts, the 300 μg dose of indacaterol significantly improved exercise endurance times on the cycle ergometer (by 88 and 111 s; p < 0.05) and significantly increased inspiratory capacity at end-exercise (by 280 and 317 ml; p < 0.05) compared with placebo. These overall findings demonstrate the clinical efficacy of indacaterol on patient-centered outcomes.
Optimun Data Quantization in Known-Signal Detection

In this section we will continue to consider the known signal in additive noise detection problem, but we will now be interested in detection based on quantized data. Instead of using the observations X i , i = 1,2,…,n , to decide between θ = 0 and θ > 0 in the model of (2–1), we will now consider detectors which use quantized versions q (X i ), where q is some piecewise-constant function.
Active Learning in Flipped Life Science Courses Promotes Development of Critical Thinking Skills

Although development of critical thinking skills has emerged as an important issue in undergraduate education, implementation of pedagogies targeting these skills across different science, technology, engineering, and mathematics disciplines has proved challenging. Our goal was to assess the impact of targeted interventions in 1) an introductory cell and molecular biology course, 2) an intermediate-level evolutionary ecology course, and 3) an upper-level biochemistry course. Each instructor used Web-based videos to flip some aspect of the course in order to implement active-learning exercises during class meetings. Activities included process-oriented guided-inquiry learning, model building, case studies, clicker-based think-pair-share strategies, and targeted critical thinking exercises. The proportion of time spent in active-learning activities relative to lecture varied among the courses, with increased active learning in intermediate/upper-level courses. Critical thinking was assessed via a pre/posttest design using the Critical Thinking Assessment Test. Students also assessed their own learning through a self-reported survey. Students in flipped courses exhibited gains in critical thinking, with the largest objective gains in intermediate and upper-level courses. Results from this study suggest that implementing active-learning strategies in the flipped classroom may benefit critical thinking and provide initial evidence suggesting that underrepresented and first-year students may experience a greater benefit.
Abstract 1266: Downregulation of PD-L1 by NSAID administration augments the effects of a multi-antigen vaccine for the prevention of adenomatous polyps in APC(Min/+) mice

Introduction: We have shown that treatment of APC(Min/+) mice with NSAIDs will inhibit development of adenomatous polyps and induce significant levels of polyp-infiltrating CD8 T-cells. We sought to identify the mechanism of NSAID induced immune stimulation and questioned whether administration of NSAIDs concurrent with vaccination could further reduce polyp formation. Methods: PD-L1 expression and T-cell infiltrates were assessed by IHC and flow cytometry. MC38 and RKO (murine/human colorectal carcinoma cell lines) were treated with naproxen (200uM-1000 uM) and harvested at 24, 48 and 72h. At 4-6 weeks, APC(Min/+) mice were given a multi-antigen peptide vaccine (COX2, CDC25B, EGFR) with CFA/IFA or adjuvant alone. Two groups received 400ppm naproxen orally 7d/wk for 18 weeks. Polyps were quantified at ≤24 weeks. Spleens and polyps were collected for IFN-gamma ELISPOT, flow cytometry, and IHC. Results: Polyps from the APC(Min/+) mouse and both cancer cell lines highly express PD-L1. PD-L1 expression was significantly decreased in MC38 (p Conclusions: NSAIDs, via modulation of PD-L1, synergize with vaccines to increase immunogenicity and enhance influx of polyp infiltrating lymphocytes. This synergy results in superior prevention of polyp formation compared to treatment with NSAID or vaccine alone and has high potential for clinical application. Citation Format: Mary L. Disis, Lauren R. Corulli, Clinton Grubbs, Ronald A. Lubet, Paul Cowan, Ekram Gad. Downregulation of PD-L1 by NSAID administration augments the effects of a multi-antigen vaccine for the prevention of adenomatous polyps in APC(Min/+) mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1266.
Moist Static Energy Budget Analysis of Tropical Cyclone Intensification in High-Resolution Climate Models

AbstractTropical cyclone intensification processes are explored in six high-resolution climate models. The analysis framework employs process-oriented diagnostics that focus on how convection, mois...
New Product Development Process Among Manufacturing Companies in Developing Countries: A Case Study

This paper reports the results of a study that examined the new product development process among manufacturers of industrial and consumer goods in Turkey. The study uses data collected by personal interviews of top executives of 60 industrial manufacturing companies in Turkey. Results indicate that in developing countries, new product development is generally simpler and less risky than in developed countries. Companies usually transfer technology and know-how, patents and licenses from industrial countries to fulfill existing demands which were previously served by imports; or they use product modifications to attract new users or to get more usage from current users. Also most companies place emphasis on the production process, product quality, cost and sales. Finally, the results are compared with a similar study conducted by the Turkish National Productivity Center for consumer products.
[Video games and smartphones : what impacts on cognitive capacities ?]

Age-related changes in mental health are an important concern in today's world. Researchers have investigated the effects of video games on mental health for the past 30 years but research on the cognitive impact of smartphones is just beginning. Studies have shown contradictory results and need to be interpreted with caution. Users should be made aware of current knowledge on their potential risks and benefits, without demonizing these relatively new technologies. They should learn how to take advantage of the great potential of these modern devices (they can for example enhance curiosity, sense of purpose and creativity) without becoming enslaved by them.
What You Get is More Than What You See – or Less -- in Models of Human Decision Making

Humans deciding between probabilistic alternatives may consider all or only some attributes of the alternatives. If they have a high need for cognition they may also engage in metacognitive monitoring that relates attributes of the presented alternatives to unpresented information. Neural network models of decision making data suggest brain interactions involved in high or low metacognitive monitoring.
Critical geographies of social robotics

Abstract This short commentary calls for further geographic engagement with emerging trends in social robotics and human-robot interaction. While the proliferation of social robots in the spaces of everyday life raises numerous empirical, ethical, and political questions, this paper argues that it also presents an opportunity to prompt theoretical debate around questions of space, intelligence, affect and emotion, and the ‘human.’
The Genetics of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is characterized by injury to the myelin sheath and subsequent neurodegeneration. The growing field of MS genetics has found that MS is at least partially heritable, with genetic risk factors that overlap with other autoimmune diseases, such as rheumatoid arthritis or type 1 diabetes. By leveraging tens of thousands of samples, more than 230 genetic risk factors have been identified for MS. Genome-wide association studies (GWAS) have helped identify important non-HLA genetic risk factors, while a growing body of work has identified both protective and risk factors located on HLA genes. This has led to more questions concerning how gene-gene or gene-environment interactions may impact MS risk and development. While these areas of inquiry have proven to be very challenging, some gene-environment interactions have been reported, and some genetic factors have been associated with relapse rate and regions of lesion burden. Mendelian randomization experiments have been successfully employed to use genetic drivers of environmental risk factors to support causal associations between these factors and MS risk, eliminating concerns for reverse causation. The study of MS genetics has led to critical insights to the pathophysiology of the disease, and future work will help to determine what shapes an individual’s experience of the disease.
Companies and Climate Change: Theory and Law in the United Kingdom

Companies lie at the heart of the climate crisis and are both culpable for, and vulnerable to, its impacts. Rising social and investor concern about the escalating risks of climate change are changing public and investor expectations of businesses and, as a result, corporate approaches to climate change. Dominant corporate norms that put shareholders (and their wealth maximization) at the heart of company law are viewed by many as outdated and in need of reform. Companies and Climate Change analyzes these developments by assessing the regulation and pressures that impact energy companies in the UK, with lessons that apply worldwide. In this work, Lisa Benjamin shows how the Paris Agreement, climate and energy law in the EU and the UK, and transnational human rights and climate litigation, are regulatory and normative developments that illustrate how company law can and should act as a bridge to progressive corporate climate action.
Sleep Buffers the Effect of Discrimination on Cardiometabolic Allostatic Load in Native Americans: Results from the Oklahoma Study of Native American Pain Risk.

Compared to other racial/ethnic groups, Native Americans (NAs) are more likely to develop health conditions associated with allostatic load (stress-related wear-and-tear). Psychosocial factors (i.e., adverse life events, discrimination, psychological distress) often promote stress and may help explain greater allostatic load in NAs. Moreover, previous research suggests sleep may either mediate or moderate the effects of some psychosocial stressors, like discrimination, on allostatic load. The current study investigated the relationship between adverse life events, discrimination, psychological stress, sleep, and cardiometabolic load. Using a sample of 302 healthy, chronic pain-free NAs and non-Hispanic White (NHW) participants, bootstrapped mediation analyses were conducted to determine whether the relationship between NA race/ethnicity and cardiometabolic allostatic load (composite score of body mass index, mean arterial pressure, and heart rate variability) was mediated by psychosocial stressors. Models also assessed whether sleep disturbance served as an additional mediator or a moderator to the effects. Consistent with prior research, we found that NAs experienced greater discrimination, adverse life events (potentially traumatic events), and cardiometabolic allostatic load than NHWs. Further, discrimination was associated with increased psychological stress for NAs, but this did not explain why NAs experience higher cardiometabolic allostatic load. A moderating effect of sleep on discrimination was found, such that discrimination partially contributed to the relationship between NA race/ethnicity and cardiometabolic allostatic load, but only for participants reporting greater sleep disturbance. Implications These findings highlight that good sleep can buffer the effect of psychosocial stress on cardiometabolic allostatic load in Native Americans.
5 – Expert Systems

An expert system is a computer program that represents and uses skills and knowledge of one or more human experts to provide high-quality performance in a specific domain. Expert systems offer a number of benefits when compared with human experts. Expertise embodied in an expert system is permanent, like other software, whereas human expertise is perishable. Expert systems can produce consistent results on the same tasks and handle similar situations consistently, whereas humans can get tired or bored and are influenced by various. Expert systems are inexpensive to operate, easy to reproduce and distribute, and can provide permanent documentation of the decision process. In addition, expert systems contain knowledge from several human experts, giving them more breadth and robustness than a single expert. Although expert systems enjoy these advantages, they also have many weaknesses that include lack of common sense knowledge, narrow focus and restricted knowledge, inability to respond creatively to unusual situations, and difficulty in adapting to changing environments.
An Ancient Queen's Code of Justice

In honor of Women's History Month, here's a brisk Occasional on the life of Boudicca, the fierce Celtic queen who nearly vanquished the Romans in 60 A.D. A pretty, melancholy essay on women, war, and outrage, it's perfect for the Anglophile or feminist with five minutes to spare.
Geographic Patterns of Land Use and Land Intensity in the Brazilian Amazon

Nearly 90 percent of agricultural land in the Brazilian Amazon is used for pasture, or has been cleared and left unused. Pasture on average is used with very low productivity. Analysis based on census tract data shows that agricultural conversion of forested areas in the wetter Western Amazon would be even less productive, using current technologies. Using census tract data from the Censo Agropecuario 1995-96, Chomitz and Thomas map indicators of current land use and agricultural productivity across Brazil's Legal Amazon. These data permit geographical resolution about 10 times finer than afforded by municipio data used in previous studies. Chomitz and Thomas focus on the extent and productivity of pasture, the dominant land use in Amazonia today. Simple tabulations suggest that most agricultural land in Amazonia yields little private economic value. Nearly 90 percent of agricultural land is either devoted to pasture or has been out of use for more than four years. About 40 percent of the currently used pastureland has a stocking ratio of less than 0.5 cattle per hectare. Tabulations also show a skewed distribution of land ownership: almost half of Amazonian farmland is located in the 1 percent of properties that contain more than 2,000 hectares. Multivariate analyses relate forest conversion and pasture productivity to precipitation, soil quality, infrastructure and market access, proximity to past conversion, and protection status. Chomitz and Thomas find precipitation to have a strong deterrent effect on agriculture. The probability that land is currently claimed, or used for agriculture, or intensively stocked with cattle, declines substantially with increasing precipitation levels, holding other factors (such as road access) constant. Proxies for land abandonment are also higher in high rainfall areas. Together these findings suggest that the wetter Western Amazon is inhospitable to exploitation for pasture, using current technologies. On the other hand, land conversion and stocking rates are positively correlated with proximity to past clearing. This suggests that in the areas of active deforestation in eastern Amazonia, the frontier is not hollow and land use intensifies over time. But this area remains a mosaic of lands with higher and lower potential agricultural value. This paper - a product of Infrastructure and Environment, Development Research Group - is part of a larger effort in the group to understand the causes and consequences of land use change. The authors may be contacted at kchomitz@worldbank.org.