cssi/SciSciGPT-SciSciNet huggingface dataset:
Palliative care and advances in cystic fibrosis: where now?

Recently-developed modulators for the cystic fibrosis transmembrane conductance regulator (CFTR) were approved by the US Food and Drug Administration for initial use in 2012.1 Major impacts from this emerging pharmacotherapy have improved nutritional status and lung function and better quality of life.2 Further, these groundbreaking CFTR modulators are expected to increase life expectancy beyond the current median US survival of 41 years.3 This will be accompanied by significant chronic symptoms and recognition of new health issues along the way. These new challenges highlight the importance of individualised palliative treatment plans to remedy existing and emerging gaps in care. Over the past decade, improvements in CF treatment have changed the face of the disease. While the current focus rightfully lies on the positive outcomes associated with CFTR modulators, redefining the disease has consequences. Moreover, increased survival into adulthood ushers in …
Abstract IA24: Immune-modulating approaches to cancer therapy: Focusing on combinations

Given the activity noted with both CTLA-4 or PD-1 blockade, clinical trials are now investigating combination checkpoint blockade. The most mature data with a combination of ipilimumab + nivolumab in melanoma showed a response rate of 60% in the context of increased yet manageable toxicity. Such responses are generally durable, even when treatment was stopped early for toxicity. Unlike in studies of PD-1 blockade monotherapy, there was no significant difference in clinical activity based on tumor expression of PD-L1. This approach has gained regulatory approval for metastatic melanoma and is in late-stage clinical trials for other malignancies. Attention is being paid to the reasons underlying the efficacy of checkpoint blockade in certain malignancies. One hypothesis has been that cancers having a high mutational load may be more amenable to immune modulation by virtue of the larger number of potential neoepitopes present, fostering baseline immune recognition that can then be potentiated by checkpoint blockade. We have found that melanoma patients having long-term clinical activity with ipilimumab have a significantly greater median number of nonsynonymous passenger mutations, compared with patients who do not respond or those who have only short-term regression. Strategies to enhance baseline immune reactivity are therefore necessary to investigate as a means to improve the impact of checkpoint blockade on a broad spectrum of cancers. The presence of suppressive myeloid cells in the tumor microenvironment also is emerging as a mechanism of resistance to the antitumor activity for checkpoint blockade. Strategies to overcome this include inhibition of CSF-1R signaling, IDO activity, and selective suppression of PI3K-γ. Citation Format: Jedd Wolchok. Immune-modulating approaches to cancer therapy: Focusing on combinations [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr IA24.
Administrative burden: Policymaking by other means

With nearly 50 years of expertise in health policy and government performance analysis between them, Herd and Moynihan’s (2019) book Administrative Burden: Policymaking by Other Means dispenses a t...
Prevalence of periapical abscesses in patients with systemic lupus erythematosus.

AIMS To assess the prevalence of periapical abscesses in patients with systemic lupus erythematosus (SLE), and to evaluate the effect of glucocorticoids (GCs) used to treat SLE, on the prevalence of such lesions. METHODS Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for SLE and periapical abscess was retrieved by searching the appropriate query in the database. The odd ratio (OR) of periapical abscesses and its association with SLE and intake of GCs were calculated and analyzed statistically. RESULTS The prevalence of periapical abscesses in patients treated with GCs was 1.5% compared to 0.39% in patients who were not treated with GCs. The OR for periapical abscesses in patients treated with GCs was 2.53 compared with OR of 0.66 in patients not treated with GCs. The differences were statistically significant (p < .0001). The prevalence of periapical abscesses in patients with SLE was 1.88%. The OR was 3.18 and the difference statistically significant (p < .0001). CONCLUSIONS Under the conditions of this study, it appears that the prevalence of periapical abscesses is higher in patients with SLE. Patients receiving GCs therapy, either for SLE or for other conditions, may present higher prevalence of periapical abscesses.
The Adrenergic System and Stem Cell-Mediated Myocardial Repair

The continuous increase of average human life span is yielding a progressively older population pool. With the aging population and increasingly sedentary lifestyle, chronic cardiovascular diseases are approaching epidemic proportions in nearly all developed countries. Decline in cardiovascular performance is counteracted by the interaction of the sympathetic (adrenergic) nervous system (ANS) and the parasympathetic system. Acutely, the elevated activity of the adrenergic system will swiftly reestablish cardiac function and return to steady levels. However, a chronic manifestation of altered cardiac function is followed by prolonged and compensatory ANS hyperactivity, which over time will lead to increased pressure on the already weakened heart. Thus far, β-receptor blockade has been the main therapeutic approach with which the inhibition of the adrenergic drive has had a positive effect counteracting the progression of cardiovascular decline. With the emergence of new discoveries in stem cell research and their possible contribution to cardiac cell turnover and tissue repair, it is critical to evaluate the extent of the impact of the ANS on cardiac regeneration via the regulation of stem cells.
SU-D-304-05: Validation of Low-Dose-Tail Modeling for Proton Pencil Beam Spot Scanning Using a Quality Assurance Test Pattern

Purpose: The purpose of this manuscript is to demonstrate the utility of a comprehensive test pattern in validating calculation models of the low-dose tails of proton pencil beam scanning (PBS) spots. Such a pattern has been used previously for quality assurance purposes to assess spot shape and location, and for determining monitor units. Methods: In this study, a scintillation detector was used to measure the test pattern in air at isocenter for two proton beam energies (115 and 225 MeV) of two IBA universal nozzles (UN). Planar measurements were compared with calculated dose distribution based on the weighted superposition of spot profiles previously measured using a pair-magnification method. Results: Including the halo component below 1% of the central dose is shown to improve the gamma-map comparison between calculation and measurement from 94.9% to 98.4% using 2 mm/2% criteria for the 115 MeV proton beam of UN #1. In contrast, including the halo component below 1% of the central dose does not improve the gamma agreement for the 115 MeV proton beam of UN #2, due to the cutoff of the halo component at off-axis locations. When location-dependent spot profiles are used for calculation instead of spot profiles at central axis,more » the gamma agreement is improved from 98.0% to 99.5% using 2 mm/2% criteria. The cutoff of the halo component is smaller at higher energies, and is not observable for the 225 MeV proton beam for UN #2. Conclusion: In conclusion, the use of a comprehensive test pattern can facilitate the validation of the halo component of proton PBS spots at off axis locations. The cutoff of the halo component should be taken into consideration for large fields or PBS systems that intend to trim spot profiles using apertures. This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17-W81XWH-07-2-0121 and W81XWH-09-2-0174.« less
Forecasting intraday volume distributions

Over the past twenty years, trading in financial markets has evolved from a human-oriented process to one that is highly automated. One of the most influential and revolutionary processes in financial markets is algorithmic trading. The focus of this work is to increase trading efficiency by improving the accuracy of intraday volume forecasts, which are used in algorithmic trading. An intraday volume forecast predicts the distribution of trading volume throughout the day, and allows traders to make better decisions regarding the timing and quantity of their trades. An accurate intraday volume forecast is an important input to trading decisions and will ultimately improve traders’ ability to meet benchmarks, such as volume weighted average price. This work seeks to understand the performance of three classes of models: moving average, exponentially weighted moving average, and average exponentially weighted moving average, for intra-day volume prediction over a large sample of U.S. equities. For each model, we explore a broad range of parameterizations and seek to understand how various factors affect model performance. Models are evaluated based on a variety of different metrics, such as mean square error and maximum absolute deviation. We report on the best performing models for a variety of stocks and scenarios. Overall, the average exponentially weighted moving average model performed the best across the examined parameters.
Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy

Background and Purpose— Cerebral amyloid angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine whether spontaneous intracerebral hemorrhage could be reduced. Methods— Tg2576 (n=16) and 5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months. Brains were extracted and stained with X-34 (to quantify amyloid), Perls’ blue (to quantify hemorrhage), and immunostained to examined β-amyloid peptide load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular markers of blood–brain barrier integrity (zonula occludins-1 [ZO-1] and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Results— Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (matrix metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Conclusions— Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse models of CAA, supporting the importance of matrix metalloproteinase–related and inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and Drug Administration–approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related intracerebral hemorrhage.
The iron-responsive element is the single element responsible for iron-dependent translational regulation of ferritin biosynthesis. Evidence for function as the binding site for a translational repressor.

Ferritin, a cytoplasmic protein critical in iron metabolism, displays iron-dependent regulation of its biosynthetic rate with no corresponding changes in mRNA levels. An iron-responsive element (IRE) has been identified in the 5′-untranslated region (UTR) of the human ferritin heavy chain mRNA which, when placed in the 5′-UTR of heterologous reporter genes, confers iron-dependent translational regulation to the hybrid mRNAs. However, whereas the biosynthetic rate of ferritin in response to changes in iron status exhibits a 30-80-fold range, the apparent ranges observed for reporter gene constructs utilizing chloramphenicol acetyltransferase assays or human growth hormone radioimmunoassays have been much less. A deletion and reconstitution study was undertaken to address the possibility that regions of the ferritin gene and mRNA other than the IRE may be necessary for the production of the full range of iron regulation. Data are presented that demonstrate that the IRE alone is capable of conferring iron-dependent translational regulation of biosynthesis to downstream encoded proteins that is both qualitatively and quantitatively similar to that observed with expression of ferritin itself. Thus, the complete range of iron-dependent translational regulation conferred by the IRE occurs independently of the presence of the ferritin promoter, other regions of the ferritin 5′-UTR, the ferritin coding region, and the ferritin 3′-UTR. Additionally, experiments addressing the translatability in vivo of various ferritin construct mRNAs support the theory that the IRE functions as the binding site for a translational repressor.
Analysis of fine granularity and building block sizes in the parallel fast messy GA

This paper presents two methods designed to improve the efficiency and effectiveness of the parallel fast messy GA used in solving the Protein Structure Prediction (PSP) problem. The first is an application of a farming model - targeting algorithm efficiency. The second successful method addresses the building block sizes used in the algorithm - targeting algorithm effectiveness.
NCAM-associated polysialic acid on ciliary ganglion neurons is regulated by polysialytransferase levels and interaction with muscle

NCAM in its high polysialic acid (PSA) form is expressed on chick hindlimb motoneurons during their growth, and then decreases at about the time that synaptogenesis is completed. In order to characterize this regulation at the cell and molecular level, the present studies use the chick ciliary ganglion (CG) system, which constitutes a homogeneous and developmentally synchronized population of motoneurons that can be used for in vitro studies. Levels of PSA in the CG were evaluated both by SDS-PAGE immunoblot analysis of total NCAM and by pulse radiolabeling of newly synthesized NCAM. Up- and downregulation of PSA expression on newly synthesized NCAM in the CG was found to be closely correlated with in vivo innervation and synaptogenesis, respectively. Moreover, the downregulation observed at synaptogenesis was prevented by in vivo blockade of neuromuscular activity with alpha-bungarotoxin. The developmental regulation of PSA expression was found to coincide precisely with an increase and decrease in levels of specific polysialyltransferase activity. By contrast, the expression of the VASE exon in NCAM, which in CNS is temporally correlated with PSA downregulation, was not expressed in the CG. Cocultures of CG neurons with myotubes were used to provide direct evidence that neuron-muscle interaction can cause a specific downregulation of both neuronal PSA and polysialyltransferase activity.
High-Temperature Corrosion of Metallic Alloys and Coatings

The sections in this article are Introduction The Basic Constituents of High-Temperature Alloys Constituents for High-Temperature Corrosion Resistance Constituents for High-Temperature Strength, Toughness, Microstructural Stability, and Creep Resistance Metallic Coatings Modes of High-Temperature Corrosion Attack Internal Oxidation Transition from Internal to External Formation Criterion for the Sustained Exclusive Growth of a Protective Scale Transient vs Steady-State Scaling Behavior Subsurface Void Formation Effects of Thermal Cycling on High-Temperature Corrosion Alloying to Resist Specific Types of High-Temperature Corrosion Sulfidation Carburization Metal Dusting Nitridation Producers of High-Temperature Alloys Acknowledgements
Options Backdating, Tax Shelters, and Corporate Culture

This Essay examines the problem of tax noncompliance through the prism of the options backdating scandal. The noncompliance of backdating was obvious, at least to tax lawyers. Backdating wasn't a sophisticated tax scheme. Rather, the noncompliance was collateral damage from weak internal controls and, in some cases, the rent-seeking of executives. Noncompliance in the face of clear rules is an overlooked problem in the corporate tax shelter literature, which tends to focus on disclosure, deterrence, or statutory interpretation. We should also study what creates the demand for tax shelters. The evidence from backdating suggests that a fast-and-loose attitude can develop when innovative companies outgrow their internal controls. When viewed in institutional context, a subset of corporate tax shelters, although adorned with more formal attire than backdating, may also be best understood as a compliance issue rather than a problem of textualism or inadequate penalties. The implication for law reform is that process matters. Culture matters. We may have more success in closing the tax gap if we support procedural changes in the way companies approach tax compliance rather than altering the substantive rules in ways that may have unintended consequences for non-fraudulent transactions.
Bone Mesenchymal Stem Cells with Growth Factors Successfully Treat Nonunions and Delayed Unions

Background While the gold standard of treatment of nonunion is open autologous bone grafting, studies have shown that injecting bone marrow aspirate concentrates (BMAC) is effective in treating tibial nonunions with fracture gaps less than 5 mm.
Binding levels of urate ions in human serum albumin and plasma.

Abstract The question of uric acid (or urate ion) binding to plasma proteins has received considerable attention in the literature. However, the actual binding level of the solute in plasma has not been satisfactorily resolved. It has now been determined that one of the major contradictions concerning reported uric acid binding levels has resulted from the use of lithium urate (prepared as a standard solution by dissolution of i g/l of uric acid in 0.6 g/l Li2CO3) instead of pure uric acid. Using a novel in vitro dynamic dialysis technique and conventional ultrafiltration techniques it was found that lithium urate exhibited binding levels of between 20–40% in 5% human serum albumin and between 35–55% in normal heparinized plasma, both at 37°. In contradistinction, binding levels of pure uric acid were about 4% in 5% human serum albumin and about 7% in normal heparinized plasma under the same conditions. This study confirms that the binding of uric acid to plasma proteins at 37° is small and probably not physiologically significant.
Parity and time-reversal anomaly in a semiconductor

The physics of a parity anomaly, potentially observable in a narrow-gap semiconductor, is revisited. Fradkin, Dagotto, and Boyanovsky have suggested [Phys. Rev. Lett. 57, 2967 (1986)] that a Hall current of anomalous parity can be induced by a Peierls distortion on a domain wall. I argue that a perturbation inducing the parity anomaly must break the time-reversal symmetry, which rules out the Peierls distortion as a potential cause. I list all possible perturbations that can generate the anomaly.
Peroxisomes take shape

Peroxisomes carry out various oxidative reactions that are tightly regulated to adapt to the changing needs of the cell and varying external environments. Accordingly, they are remarkably fluid and can change dramatically in abundance, size, shape and content in response to numerous cues. These dynamics are controlled by multiple aspects of peroxisome biogenesis that are coordinately regulated with each other and with other cellular processes. Ongoing studies are deciphering the diverse molecular mechanisms that underlie biogenesis and how they cooperate to dynamically control peroxisome utility. These important challenges should lead to an understanding of peroxisome dynamics that can be capitalized upon for bioengineering and the development of therapies to improve human health.
Epigenetic aberrations during oncogenesis

The aberrant epigenetic landscape of a cancer cell is characterized by global genomic hypomethylation, CpG island promoter hypermethylation of tumor suppressor genes, and changes in histone modification patterns, as well as altered expression profiles of chromatin-modifying enzymes. Recent advances in the field of epigenetics have revealed that microRNAs’ expression is also under epigenetic regulation and that certain microRNAs control elements of the epigenetic machinery. The reversibility of epigenetic marks catalyzed the development of epigenetic-altering drugs. However, a better understanding of the intertwined relationship between genetics, epigenetics and microRNAs is necessary in order to resolve how gene expression aberrations that contribute to tumorigenesis can be therapeutically corrected.
A framework of theoretical lenses and strategic purposes to describe relationships among firm environmental strategy, financial performance, and environmental performance

Purpose – The purpose of this paper is to investigate whether the type of theoretical lens and strategic purpose impacts the relationships among firm environmental strategy, financial performance, and environmental performance.Design/methodology/approach – This is a theoretical paper which first investigates three constructs: firm environmental strategy, environmental performance, and economic performance. Scholars have argued for different relationships among the three constructs. The paper then discusses two theoretical lenses (strategic choice and the resource‐based view) and two strategic purposes (stakeholder and shareholder) used in the literature. The paper argues that the type of theoretical lens and strategic purpose will impact the way the three constructs (firm environmental strategy, financial performance, and environmental performance) are arranged.Findings – The paper provides a two‐by‐two matrix distinguishing between theoretical lens and strategic purpose. The paper argues that the specifi...
The history and background of astrodynamics

Abstract The history of astrodynamics began with Newton's Principia, 300 years ago. Newton's laws of motion and law of gravitation, with small modifications, are still applicable today and are being used in space research. The orbiting of the first artificial satellite renewed interest in celestial mechanics which applied the Newtonian laws to the motion of natural bodies. The space applications and the study of the dynamics of artificial bodies introduced several changes in the basic requirements and astrodynamics became the basic research tool in space dynamics. The original contributors in the U.S. to this field were Herrick, Herget, Eckert, Clemence and Brouwer whose influence is still strongly felt, mostly through their many valuable publications, associates, and students.
A diastereoselective synthesis of (±) trichodiene

Abstract A route to the total synthesis of the title compound is described. The key step involves the [3,3] sigmatropic of the silyl keteneacetal derived from an allylic β-ketoester. The potential application of this protocol to the construction of the higher trichothecenes is also discussed.
Rumen volatile fatty acids and milk composition from cows fed hay, haylage, or urea-treated corn silage.

Alfalfa-brome hay, haylage, .5% urea-treated corn silage, or .5% urea plus 1% dried whey-treated corn silage was fed as the only forage to one of four groups of 10 lactating cows per group for a lactation trial of 10 wk. Rumen samples were collected via stomach tube 3 to 4 h after the morning feeding. The pH of the rumen samples from cows fed hay was higher than for cows fed haylage, urea-treated corn silage, and urea-whey corn silage, 6.69 versus 6.36, 6.40, and 6.50. Total volatile fatty acids and propionate were highest from cows fed urea-whey corn silage and were higher on all three fermented forages than cows fed hay. Acetate/propionate ratio was highest from cows fed hay and lowest from cows fed corn silages. Butyrate was highest from cows fed haylage or hay. Milk protein composition was not affected by ration although nonprotein nitrogen of milk was highest from cows fed the urea-treated corn silages. Oleic acid and total unsaturated fatty acids were lowest in milk fat from cows fed hay while palmitic acid was highest from cows fed hay and haylage. These results suggest that type of forage fed may cause small changes in rumen fermentation and in milk composition. The importance of these changes is unknown but may affect properties of dairy products produced from this milk.
Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors

Membrane recruitment of cytohesin family Arf guanine nucleotide exchange factors depends on interactions with phosphoinositides and active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an unknown structural mechanism. Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory elements in addition to the PH domain. The crystal structure of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosphatidyl inositol 3,4,5-trisphosphate and N-terminally truncated Arf6-GTP reveals a large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestration of the autoinhibitory elements in grooves at the Arf6/PH domain interface. Disposition of the known membrane targeting determinants on a common surface is compatible with multivalent membrane docking and subsequent activation of Arf substrates, suggesting a plausible model through which membrane recruitment and allosteric activation could be structurally integrated.
Effects of soman and sarin on high affinity choline uptake by rat brain synaptosomes

Abstract Synaptosomes were incubated at various time intervals following injection of 120 μg/kg SC of soman or sarin or with various concentrations (10 −8 to 10 −2 M) of soman or sarin in vitro. Total cholinesterase (ChE) activities in each brain region were also measured. Following soman injection, sodium-dependent, high affinity choline uptake (SDHACU) was decreased from 1 to 4 hr in the cortex and from 1 to 2 hr in the hippocampus, but increased from 2 to 24 hr in the striatum. Similarly, following sarin injection SDHACU was decreased at 0.5 hr in the cortex and from 1 to 4 hr in the hippocampus, but increased at 1 hr in the striatum. Injection of soman severely inhibited (83–99%) total ChE activity in the cortex, hippocampus and striatum from 1 to 24 hr. In contrast, sarin did not severely inhibit ChE activity in these regions and maximal inhibition (40–60%) did not occur until 24 hr after injection. With both compounds, by 168 hr ChE activity in all regions had partially recovered. Incubation of synaptosomes with soman or sarin in vitro at concentrations below 10 −4 M did not affect SDHACU in any of the brain regions. These data demonstrated that acute soman and sarin injection produced similar effects upon SDHACU in different brain regions, although the time-course of these effects was different for the two compounds. These effects were probably neither due to a direct action of these compounds on the uptake process nor dependent on ChE inhibition.
The particle track record of the Sea of Plenty.

We have measured the particle track densities in 36 grains taken from two levels of the soil column returned from the Sea of Plenty by Luna 16. One sample is from near the surface, the other is from about 30 cm depth. All but one of the grains contained very high track densities. We conclude that all of the Luna 16 soil has been irradiated very close to the surface, that there has been little or no 'recent' admixture of previously shielded material from below 30 cm, and that the regolith is both unusually thin at the Luna 16 site and extremely old (about 3 b.y. and more).
Variability of sea ice simulations assessed with RGPS kinematics

[1] Sea ice drift and deformation from coupled ice-ocean models are compared with high-resolution ice motion from the RADARSAT Geophysical Processor System (RGPS). In contrast to buoy drift, the density and extent of the RGPS coverage allows a more extensive assessment and understanding of model simulations at spatial scales from ∼10 km to near basin scales and from days to seasonal timescales. This work illustrates the strengths of the RGPS data set as a basis for examining model ice drift and its gradients. As it is not our intent to assess relative performance, we have selected four models with a range of attributes and grid resolution. Model fields are examined in terms of ice drift, export, deformation, deformation-related ice production, and spatial deformation patterns. Even though the models are capable of reproducing large-scale drift patterns, variability among model behavior is high. When compared to the RGPS kinematics, the characteristics shared by the models are (1) ice drift along coastal Alaska and Siberia is slower, (2) the skill in explaining the time series of regional divergence of the ice cover is poor, and (3) the deformation-related volume production is consistently lower. Attribution of some of these features to specific causes is beyond our current scope because of the complex interplay between model processes, parameters, and forcing. The present work suggests that high-resolution ice drift observations, like those from the RGPS, would be essential for future model developments, improvements, intercomparisons, and especially for evaluation of the small-scale behavior of models with finer grid spacing.
Nurse practitioners' perceptions and participation in pharmaceutical marketing.

Title. Nurse practitioners’ perceptions and participation in pharmaceutical marketing. Aim. This paper reports on a study conducted to describe family nurse practitioners’ perceptions towards and participation in pharmaceutical marketing and to explore the relationships among related variables. Background. The pharmaceutical industry’s intense global marketing strategies have resulted in widespread concern in healthcare professionals and professional groups, sectors of the public in many countries, and in the World Health Organization. Research on healthcare providers’ participation in pharmaceutical marketing indicates that these relationships are conflicts of interests and compromise healthcare providers’ prescribing practices and trust. Nursing, as a discipline, appears to be slow to address the impact of pharmaceutical marketing on nursing practice. Method. Questionnaires about perceptions and participation in pharmaceutical marketing were completed by a random sample of 84 licensed family nurse practitioners in the United States of America in 2007. Findings. Family nurse practitioners viewed pharmaceutical company marketing uncritically as educational and beneficial. They also perceived other providers but not themselves as influenced by pharmaceutical marketing. The findings supported those found in previous research with nurses and physicians. Conclusion. Lack of education, participation in marketing and psychological and social responses may impede family nurse practitioners’ ability to respond critically and appropriately to marketing strategies and the conflict of interest it creates.
Effects of simulated upwelling and oligotrophy on chemostat-grown natural marine phytoplankton assemblages☆

Abstract Natural phytoplankton assemblages from the Scripps Pier were grown in two chemostats under conditions that simulated two rates of upwelling followed by oligotrophic conditions. At a moderate upwelling rate ( D = 0.3·day −1 ) centric diatoms were selected, while at a low rate ( D = 0.1·day −1 ) a mixture of species dominated. Pumping of low-nutrient water (oligotrophy) resulted in a mixture of species at both rates. Upwelling at a high rate decreased diversity of the crop as compared with the low rate or oligotrophy. These results are compared with those of others who have subjected natural assemblages to continuous culture.
Surgical Management of Coronary Insufficiency in a Child with Kawasaki's Disease: Use of Bilateral Internal Mammary Arteries

Coronary insufficiency is an important sequela of Kawasaki's disease. Successful myocardial revascularization with saphenous vein grafts and, more recently, with internal mammary artery grafts has been performed. We report a case of Kawasaki's disease with chronic coronary insufficiency in which complete myocardial revascularization was accomplished using bilateral internal mammary arteries, and we present a review of the literature.
Inactivation of transforming DNA by ultraviolet light. II. Protection by histidine against near-UV irradiation: action spectrum.

Abstract Histadine, at concentrations greater than 0.075 M , quenches the inhibition of the transforming activity of DNA by near UV. This effect does not occur at wavelengths below about 300 nm and is maximal at about 380 nm. Since histidine at this concentration has no effect upon the inactivation by far UV, this observation shows that inactivation by near UV is clearly different, and suggests an indirect photosensitization mechanism. The histidine protection spectrum coincides closely with the near-UV DNA inactivation spectrum derived from the shoulder in the near UV.
Nephrotic syndrome and interstitial nephritis associated with celecoxib

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to cause fluid and electrolyte abnormalities and renal failure. NSAIDs also may cause an acute allergic interstitial nephritis (AIN) and the nephrotic syndrome, characterized by histologic pathology consistent with minimal change disease in patients with previously normal renal function. The nephrotoxic potential of cyclooxygenase 2 (COX-2) inhibitors has not been established because AIN associated with nephrotic syndrome has not been reported secondary to the COX-2 inhibitors. This case report describes the first case of AIN associated with nephrotic syndrome in a patient treated with the selective COX-2 inhibitor, celecoxib.
Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy

From June 19, 1975 to December 22, 1976, twenty-seven patients with advanced Hodgkin's disease who failed MOPP (nitrogen mustard, vincristine, procarbazine and prednisone) were treated with adriamycin, bleomycin, vinblastine, and imidazole carboxamide, (ABVD). Complete response (CR) was achieved in 22% of patients and partial response was achieved in 15%. No response was observed in 63% of patients. With a median duration of follow-up for CR patients of only 10.5 months, two of the six CR patients have already relapsed. In this series of patients ABVD was not an effective curative regimen for patients with Hodgkin's disease who have failed MOPP.
Ambient light levels and critical care outcomes

Abstract Purpose Guidelines for the construction of critical care units require windows in room design to ensure a contribution of natural sunlight to ambient lighting. However, few studies have been published with evidence assessing this recommendation. We investigated the association of ambient light levels with clinical outcomes and sedative/analgesic/neuroleptic use in a medical intensive care unit (MICU). Methods This is a retrospective, observational study at a tertiary care facility with a 29-bed MICU. First/single MICU admissions between April 19, 2006, and June 30, 2009 (N = 3577), were analyzed with respect to clinical outcomes and sedation use according to MICU room orientation and corresponding light levels. Results Light levels were low but varied among the 4 room orientations. There were no significant differences in MICU mortality (north, 14.0%; east, 13.5%; west, 16.2%; south, 15.6%; P = .451), hospital mortality (20.8%, 20.9%, 22.2%, 22.3%; P = .796), 28-day intensive care unit–free days (17.6 ± 10.2, 18.0 ± 10.1, 17.7 ± 10.5, 17.2 ± 10.4; P = .555), 28-day ventilator-free days (16.3 ± 11.1, 16.5 ± 11.1, 15.5 ± 11.5, 15.4 ± 11.4; P = .273). No clinically significant differences in intravenous sedative/analgesic use occurred across room orientations. Conclusions Despite differing ambient light, room orientation was not associated with critical care outcomes or differences in sedative/analgesic/neuroleptic use. Current guidelines positing that windows alone are necessary or sufficient for MICU room light management may require further investigation and consideration.
Observations of Horizontal Velocities and Vertical Displacements in the Equatorial Pacific Ocean Associated with the Early Stages of the 1982/83 El Niño

Abstract Pacific near-equatorial absolute-velocity data and CTD–O2 observations collected from the R.V. Conrad in the northern fall of 1982 are presented. Quite by chance, the cruise took place during the early stages of the 1982/83 El Nino. The data obtained are generally consistent with the fundamental ideas about El Nino onset, in that abnormal eastward flow near the surface and large thermocline depressions were observed. These changes are quantified by comparing with previously collected data and are discussed in terms of simple equatorially-trapped wave dynamics. The results indicate that first- and second-mode disturbances, probably Kelvin waves, were prominent in the equatorial Pacific in the fall of 1982.
Fracture and the risk of coronary events in women with heart disease

Abstract Background Osteoporosis is associated with aortic calcification and cardiovascular mortality. However, whether skeletal fractures predict the risk of coronary events is unknown. Methods We used Cox proportional hazards models to determine whether postmenopausal fracture was associated with the risk of coronary heart disease events among the 2763 postmenopausal women with known coronary disease enrolled in the Heart and Estrogen/progestin Replacement Study. Because fractures occurred before enrollment (in 615 women) and during follow-up (in 276 women), we treated incident fracture as a time-dependent covariate in our models. Results During a mean follow-up of 4.1 years, 361 women had coronary heart disease events. The risk of these events was 25% lower in women who sustained fractures than in those without fractures (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.57 to 0.96; P = 0.02). This association was not confounded by physical activity or by factors associated with both fracture and coronary heart disease events (HR = 0.75; 95% CI: 0.57 to 0.98; P = 0.04). Conclusion Postmenopausal women with heart disease who had skeletal fractures had a reduced risk of subsequent coronary events. This unexpected association, if confirmed in future studies, could influence risk-related treatment strategies for cardiovascular disease.
Effects of Disorientation on Human Spatial Cognition: Object Localization in Virtual Environments

The present research examines the effects of disorientation on human ability to locate objects in space in a virtual environment (VE). Participants were asked to memorize the location of virtual objects. After memorizing object locations, they were asked to indicate where the objects were located while inside a virtual chamber. This procedure was repeated in eyes-closed and disoriented conditions. Subject pointing responses were used to measure memory for the relative location of objects in virtual space. This method was extended from Wang and Spelke's (2000) research in a real-world setting. The results show systematic individual differences in the effects of disorientation on the ability to locate objects in space. Two groups of subjects, initially disoriented in the eyes-closed condition, use a memory strategy to locate objects, while another group, less easily disoriented in eyes-closed, shows degraded performance in the disorientated condition. The results are discussed with respect to configural and...
The 1,3 B 1 — 1 A 1 systems of the nitrite anion in a NaHCO 2 host crystal

Abstract The lower energy electronic transitions of the NO −2 anion in a NaHCO 2 host crystal at 4 K are reported and analyzea. The 1B 1— 1A 1 system, whose origin is at 25 649 cm −1, is seen in absorption and fluorescence accompanied by a long progression in the symmetric bending mode (ν′ 2 = 626, ν″ = 820 cm −1). The implied change in the ONO bond angle is 9 ± 3 0. The 3B 1 → 1A 1 phosphorescence is quite weak with an extrapolated origin at 18 059 cm −1. The 1B 1 ← 1A 1 absorption linewidths, the lower-resolution fluorescence photoexcitation spectrum, and the relative phosphorescence and fluorescence intensities suggest the involvement of an intermediate state in populating the triplet manifold after excitation of the 1B 1 state.
Electroweak properties of two-nucleon systems in lattice QCD

We discuss a method by which lattice QCD simulations can be used to determine the electroweak properties of two-nucleon systems. In particular, we demonstrate that numerical calculations of two-particle energy levels in a finite volume immersed in background electroweak fields can determine the deuteron magnetic moment, the cross-section for thermal neutron capture n p → d γ and the cross-section for neutrino breakup of the deuteron, ν d → n p ν . The last of these processes is only poorly constrained experimentally and will provide a large source of uncertainty in future extractions of neutrino mass and mixing parameters from the Sudbury Neutrino Observatory.
Durable, efficient, and economical electronic toilet-training devices for use with retarded children

Instrumented behavior observation and modification is typically an expensive process, yet the instruments used are often relatively simple and limited in function. Two sets of electronic devices were constructed to aid in training correct toileting behavior with retarded children. The body-worn alerting unit monitors the residents’ elimination as he moves through his environment. This set consists of a moisture detection circuit enclosed in a durable plastic box which is worn by the resident in either a harness or vest. The body-worn alerting unit is connected, via a cord, to underwear which have pliable wires running along their midline. The other set of units monitors elimination on a commode or toilet, and consists of a signaling box containing the moisture-detection circuit and a circular plate which is hung on the toilet or commode. Over 3 years of field testing have shown the units to be very durable and efficient.
Examining modality usage in a conversational multimodal application for mobile e-mail access

As Third Generation (3G) networks emerge they provide not only higher data transmission rates but also the ability to transmit both voice and low latency data within the same session. This paper describes the architecture and implementation of a multimodal application (voice and text) that uses natural language understanding combined with a WAP browser to access email messages on a cell phone. We present results from the use of the system by users as part of a laboratory trial that evaluated usage. The user trial also compared the multimodal system with a text-only system that is representative of current products in the market today. We discuss the observed modality issues and highlight implementation problems and usability concerns that were encountered in the trial. Findings indicate that speech was used the majority of the time by participants for both input and navigation even though most of the participants had little or no prior experience with speech systems (yet did have prior experience with text-only access to applications on their phones). To our knowledge this represents the first implementation and evaluation of its kind using this combination of technologies on an unmodified cell phone. Design implications resulting from the study findings and usability issues encountered are presented to inform the design of future conversational multimodal mobile applications.
Atmospheric heat fluxes and restoration of the circumglobal equatorial current

An analytical model is developed for estimating the heat fluxes in the lower and upper parts of the atmosphere that would result from possible increases in the carbon dioxide (CO 2 ) concentrations and the ensuing temperature changes. For a doubling of the CO 2 concentration by volume, the net heat flux to the troposphere is estimated to increase by 22 percent, and for a quadrupling of the concentration, the net heat flux increases by 39 percent, implying an enhanced energy input to the troposphere where weather phenomena are initiated.
Adaptive thermogenesis in humans

The increasing prevalence of obesity and its comorbidities reflects the interaction of genes that favor the storage of excess energy as fat with an environment that provides ad libitum availability of energy-dense foods and encourages an increasingly sedentary lifestyle. Although weight reduction is difficult in and of itself, anyone who has ever lost weight will confirm that it is much harder to keep the weight off once it has been lost. The over 80% recidivism rate to preweight loss levels of body fatness after otherwise successful weight loss is due to the coordinate actions of metabolic, behavioral, neuroendocrine and autonomic responses designed to maintain body energy stores (fat) at a central nervous system-defined 'ideal'. This 'adaptive thermogenesis' creates the ideal situation for weight regain and is operant in both lean and obese individuals attempting to sustain reduced body weights. Much of this opposition to sustained weight loss is mediated by the adipocyte-derived hormone 'leptin'. The multiple systems regulating energy stores and opposing the maintenance of a reduced body weight illustrate that body energy stores in general and obesity in particular are actively 'defended' by interlocking bioenergetic and neurobiological physiologies. Important inferences can be drawn for therapeutic strategies by recognizing obesity as a disease in which the human body actively opposes the 'cure' over long periods of time beyond the initial resolution of symptomatology.
The influence of histamine and serotonin in promoting early uterine growth in the rat

Abstract Previous studies from these laboratories demonstrated that estrogen-induced histamine release, or histamine itself, may trigger the acute vasodilatation, hyperemia, and increase in capillary permeability which permit the accumulation of electrolytes, water and other metabolites in the stimulated target. These investigations have been extended to serotonin and heparin. Heparin was without effect 4 or 24 hr after intrauterine administration to adult ovariectomized rats. Serotonin, on the other hand, exhibited a striking similarity to histamine in its early influence on uterine vascularity and water imbibition, and was approximately 17 times as effective on a molar basis. Mitotic activity in the epithelium was conspicuous 24 hr after histamine treatment. Serotonin had a similar but less intense influence on epithelial mitoses. Intraluminally administered LSD-25 inhibited the hyperemia and water imbibition due to estrogen, even in adrenalectomized animals. Whether serotonin, which exhibits the estrogenicomimetic properties of histamine, normally functions in this capacity under circumstances associated with hormonal action remains to be determined.