bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms
Authors: Reinecke Isabel , Schultze‐Mosgau Marcus‐Hillert , Nave Rüdiger , Schmitz Heinz , Ploeger Bart A. 
Published: December 2016

AbstractPharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure‐response relationship focusing on the development of large ovarian follicle‐like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone‐binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose‐finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure‐response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation.
Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance
Authors: Ciavatta Maria Letizia , Lefranc Florence , Carbone Marianna , Mollo Ernesto , Gavagnin Margherita , Betancourt Tania , Dasari Ramesh , Kornienko Alexander , Kiss Robert 
Published: December 2016

AbstractThe chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cellsin vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activityin vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.
Animated Activity Questionnaire (AAQ), a new method of self‐reporting activity limitations in patients with hip and knee osteoarthritis: Comparisons with observation by spouses for construct validity
Authors: Peter W.F. , Dagfinrud H.S. , Østerås N. , Terwee C.B. 
Published: December 2016

AbstractObjectiveThe aim of the present study was to evaluate the construct validity of the Animated Activity Questionnaire (AAQ) for measuring activity limitations of patients with hip and knee osteoarthritis (HKOA).DesignIn a psychometric design, data from HKOA patients and their spouses in Norway and the Netherlands were collected independently of each other, using the AAQ, the Function of Daily Living (FDL) subscale from the Hip disability or Knee injury Osteoarthritis Outcome Scale (H/KOOS) and the Numerical Rating Scale for pain (NRS‐pain). By showing standardized animations on a computer, the AAQ minimizes the influence of the patient's own frame of reference. Therefore, we expected a strong correlation (≥ 0.6) for the AAQ, between patients and spouses. By contrast, we expected a moderate correlation (0.3–0.6) between patients and spouses on the H/KOOS and the NRS‐pain. Analyses were carried out by partial correlations.ResultsIn total, 29 Norwegian and 30 Dutch patients with HKOA and their spouses participated. A high correlation between patient and spouse scores on the AAQ (r = 0.61) was confirmed, but the correlations between patient and spouses scores on the H/KOOS FDL subscale (0.55) and NRS‐pain (0.64) were higher than expected, indicating that spouses may have insight not only into the observed activity limitations of the patient (as measured by the AAQ), but also into patients' subjectively perceived activity limitations (as measured by written questionnaires).ConclusionsThe construct validity of the AAQ was supported by a high correlation between patients' and spouses' scores. Our hypothesis that spouses are less influenced by patients' subjective frame of reference in responding to self‐report questionnaires may not be correct.
The role of enjoyment in exercise for people with arthritis: Four different viewpoints from a Q‐methodology study
Authors: Kibblewhite Julia R. , Hegarty Roisin S. M. , Stebbings Simon , Treharne Gareth J. 
Published: December 2016

AbstractPurposeThere is limited research on the role of enjoyment of exercise among people with arthritis. The aim of the present study was to determine distinct viewpoints on exercise held by people with arthritis, and how enjoyment features in these viewpoints.MethodsA Q‐methodology study was conducted, which involved two interviews with people with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis (aged 20–85 years). In the first interviews, 11 participants helped to create the Q‐set, a set of statements reflecting a range of existing views on exercising. In the second interviews, 12 participants (nine of the 11 from the first interviews and three others) ranked the Q‐set on a forced quasi‐normal distribution of agreement. A Q‐method factor analysis was carried out to determine groupings of participants with similar views on exercise.ResultsFour groupings were discovered, and defined in terms of rankings of statements and illustrative quotes from the ranking procedure. The first grouping had all changed their exercise habits after diagnosis with arthritis. The second grouping had a shared enjoyment for walking to stay healthy. The third grouping's viewpoints focused on knowledge about how much exercise they should carry out. The fourth grouping shared a sense of importance of being responsible for their health by exercising.ConclusionThese findings provide information about the role that enjoyment plays in motivating people with arthritis to exercise, although enjoyment of exercise was not expressed by all participants. People with arthritis who share these viewpoints on exercise enjoyment may require different forms of advice regarding feasible and enjoyable exercise.
Population‐level decline in BMI and systolic blood pressure following mass HIV treatment: Evidence from rural KwaZulu‐Natal
Authors: Geldsetzer Pascal , Feigl Andrea B. , Tanser Frank , Gareta Dickman , Pillay Deenan , Bärnighausen Till 
Published: December 2016

ObjectiveClinic‐based studies have shown that patients with human immunodeficiency virus (HIV) gain weight after initiation of antiretroviral therapy (ART). This study aimed to determine whether the scale‐up of ART was associated with a population‐level increase in body mass index (BMI) and blood pressure (BP) in a community with high HIV and obesity prevalence.MethodsA household survey was conducted in rural KwaZulu‐Natal before ART scale‐up (in 2004) and when ART coverage had reached 25% (in 2010). Anthropometric data was linked with HIV surveillance data.ResultsMean BMI decreased in women from 29.9 to 29.1 kg/m2 (P = 0.002) and in men from 24.2 to 23.0 kg/m2 (P < 0.001). Similarly, overweight and obesity prevalence declined significantly in both sexes. Mean systolic BP decreased from 123.0 to 118.2 mm Hg (P < 0.001) among women and 128.4 to 123.2 mm Hg (P < 0·001) among men.ConclusionsLarge‐scale ART provision is likely to have caused a decline in BMI at the population level, because ART has improved the survival of those with substantial HIV‐related weight loss. The ART scale‐up may have created an unexpected opportunity to sustain population‐level weight loss in communities with high HIV and obesity prevalence though targeted lifestyle and nutrition interventions.
Association of a gain‐of‐function variant in LGR4 with central obesity
Authors: Zou Yaoyu , Ning Tinglu , Shi Juan , Chen Maopei , Ding Lin , Huang Ya , Kauderer Sophie , Xu Min , Cui Bin , Bi Yufang , Liu Simin , Hong Jie , Liu Ruixin , Ning Guang , Wang Jiqiu 
Published: December 2016

ObjectiveTo determine the relationship of the gain‐of‐function variant A750T in leucine‐rich repeat containing G protein‐coupled receptor 4 (LGR4) with central obesity and related metabolic phenotypes.MethodsThe LGR4 A750T (c.2248 G > A) variant was detected by Sanger sequencing in a discovery young population and a validation community‐based population with obesity from eastern China. Fat indices determined by anthropometry and computed tomography scans and clinical biochemical measurements were collected for association analysis.ResultsLGR4 A750T was significantly correlated with waist circumference (P = 0.030) and waist‐to‐height ratio (P < 0.001) in the young cohort (N = 594) and with waist‐to‐hip ratio (P = 0.013) in the community population (N = 1067). Combined analysis showed a significant correlation of the variant with waist circumference (P < 0.001) and waist‐to‐hip ratio (P = 0.021). Moreover, the variant had a remarkable correlation with abdominal visceral fat area (P = 0.004) and was associated with 2‐h plasma insulin (P = 0.009) and the Matsuda index (P = 0.027) after an oral glucose tolerance test in young subjects with obesity.ConclusionsThe LGR4 A750T variant may contribute to central obesity characterized by abdominal visceral fat accumulation.
Influence of propeller slipstream on vortex flow field over a typical micro air vehicle
Authors: Sudhakar S. , Chandankumar A. , Venkatakrishnan L. 
Published: December 2016

ABSTRACTAn experimental study has been carried out to explore the effect of propeller-induced slipstream on the vortex flow field on a fixed-wing Micro Air Vehicle (MAV). Experiments were conducted at a freestream velocity of 10 m/s, corresponding to a Reynolds number based on a root chord of about 1.6 × 105. Surface flow topology on the surface of the MAV wing at propeller-off and propeller-on conditions was captured using surface oil flow visualisation at four angles of incidence. The mean off-body flow over the MAV was documented in the four spanwise planes at different chord position using Stereoscopic Particle Image Velocimetry (SPIV) technique at angle-of-attack of 24° for both conditions. The oil flow visualisation showed minimal differences in flow patterns for propeller-off and propeller-on conditions at 10° and 15° incidence. The small asymmetry between port and starboard side observed at 20° during the propeller-off condition became significantly pronounced at 24°. The fuselage stub which is necessary for housing the motor of the propeller was seen to have a significant effect on the flow symmetry at large incidences that can occur when the MAV encounters sudden vertical gusts. Switching on the propeller restored the symmetry at both incidences. SPIV measurements were carried out at the incidence of 24° which exhibited the highest asymmetry. The off-body data shows the re-establishment of symmetry during propeller-on condition owing to the increase in the magnitude of spanwise and vertical velocities as a result of the propeller slipstream. The findings emphasise the importance of considering the propeller flow and design of the motor housing while evaluating the aerodynamics of low-aspect-ratio MAVs.
Donaldsonian Themes: A Commentary
Authors: Donaldson Thomas 
Published: December 2016

ABSTRACT:The articles in the special issue ofBusiness Ethics Quarterly(2015), “Normative Business Ethics in a Global Economy: New Directions on Donaldsonian Themes,” were written by a set of outstanding scholars: Margaret M. Blair, Joseph P. Gaspar, Nien-hê Hsieh, Peter L. Jennings, Marietta Peytcheva, Andreas Georg Scherer, Amy J. Sepinwall, Andrew Stark, Danielle E. Warren, and Manuel Velasquez. In this commentary I reply to my colleagues, arranging my reply around the following themes: 1) the corporate moral agent; 2) the idea of a social contract for business; 3) managing ethics within corporations; and 4) values in business. I discuss each in turn. However, I reflect first on my idiosyncratic approach to business ethics.
Clostridium difficile in an Urban, University-Affiliated Long-Term Acute-Care Hospital
Authors: Jacob Jerry , Wu Jingwei , Han Jennifer , Nelson Deborah B. 
Published: December 2016

OBJECTIVESTo describe the characteristics and impact of Clostridium difficile infection (CDI) in a long-term acute-care hospital (LTACH).DESIGNRetrospective matched cohort study.SETTINGA 38-bed, urban, university-affiliated LTACH.METHODSThe characteristics of LTACH-onset CDI were assessed among patients hospitalized between July 2008 and October 2015. Patients with CDI were matched to concurrently hospitalized patients without a diagnosis of CDI. Severe CDI was defined as CDI with 2 or more of the following criteria: age ≥65 years, serum creatinine ≥2 mg/dL, or peripheral leukocyte count ≥20,000 cells/μL. A conditional Poisson regression model was developed to determine characteristics associated with a composite primary outcome of 30-day readmission to an acute-care hospital, or mortality.RESULTSThe overall incidence of CDI was 21.4 cases per 10,000 patient days, with 27% of infections classified as severe. Patients with CDI had a mean age of 70 years (SD, 14 years), a mean Charlson comorbidity index of 3.6 (SD, 2.0), a median length of stay of 33 days (interquartile range [IQR], 24–45 days), and a median time between admission and CDI diagnosis of 16 days (IQR, 9–23 days). The most commonly prescribed antibiotic preceding a CDI diagnosis was a cephalosporin, with median duration of 8 days (IQR, 4–14 days). In multivariate analysis, CDI was not significantly associated with the primary outcome (relative risk, 0.97; 95% CI, 0.59–1.58).CONCLUSIONSIncidence of CDI in an urban, university-affiliated LTACH was high. Future research should focus on infection prevention measures to decrease the burden of CDI in this complex patient population.Infect Control Hosp Epidemiol 2017;38:294–299
A model for confined vortex rings with elliptical-core vorticity distribution
Authors: Danaila Ionut , Kaplanski Felix , Sazhin Sergei S. 
Published: December 2016

We present a new model for an axisymmetric vortex ring confined in a tube. The model takes into account the elliptical (elongated) shape of the vortex ring core and thus extends our previous model (Danaila et al. J. Fluid Mech., vol. 774, 2015, pp. 267–297) derived for vortex rings with quasi-circular cores. The new model offers a more accurate description of the deformation of the vortex ring core, induced by the lateral wall, and a better approximation of the translational velocity of the vortex ring, compared with the previous model. The main ingredients of the model are the following: the description of the vorticity distribution in the vortex ring is based on the previous model of unconfined elliptical-core vortex rings (Kaplanski et al. Phys. Fluids, vol. 24, 2012, 033101); Brasseur’s approach (Brasseur, NASA Tech. Rep. JIAA TR-26, 1979) is then applied to derive a wall-induced correction for the Stokes streamfunction of the confined vortex ring flow. We derive closed formulae for the flow streamfunction and vorticity distributions. An asymptotic expression for the long-time evolution of the drift velocity of the vortex ring as a function of the ellipticity parameter is also derived. The predictions of the model are shown to be in agreement with direct numerical simulations of confined vortex rings generated by a piston–cylinder mechanism. The predictions of the model support the recently suggested heuristic relation (Krieg & Mohseni Trans. ASME J. Fluids Engng, vol. 135, 2013, 124501) between the energy and circulation of vortex rings with converging radial velocity. A new procedure for fitting experimental and numerical data with the predictions of the model is described. This opens the way for applying the model to realistic confined vortex rings in various applications including those in internal combustion engines.
New Cretaceous lungfishes (Dipnoi, Ceratodontidae) from western North America
Authors: Frederickson Joseph A. , Cifelli Richard L. 
Published: December 2016

AbstractCeratodontid lungfishes are generally rare, poorly represented elements of North America’s Mesozoic ecosystems, with previously known maximum diversity in the Late Jurassic. Herein we describe four new species of the form genusCeratodus, from the Cretaceous of the Western Interior, considerably expanding fossil representation of post-Triassic dipnoans in North America. To model taxonomic and morphologic diversity, we adopt a four-fold system of phenetically based species groups, named for exemplars from the Morrison Formation.Ceratodus kirklandin. sp. (Potamoceratodus guentherigroup) andC.kempaen. sp. (C.frazierigroup) represent a hitherto unsampled time interval, the Valanginian.Ceratodus nirumbeen. sp. andC.molossusn. sp. extend the temporal ranges of theC.fossanovumandC.robustusgroups upward to the Albian and Cenomanian, respectively. These new occurrences show that ceratodontids maintained their highest diversity from the Late Jurassic through the mid-Cretaceous (Albian–Cenomanian), an interval of ~60 Myr. The existing record suggests that some of the later (mid-Cretaceous) ceratodontids may have been tolerant of salt water; to date, there is no evidence that they aestivated. Only a few occurrences are known from horizons younger than Cenomanian. Demise of ceratodontids appears to be part of a broader pattern of turnover that occurred at the Cenomanian-Turonian boundary in North America.
The first Neogene record ofZygolophodon(Mammalia, Proboscidea) in Thailand: implications for the mammutid evolution and dispersal in Southeast Asia
Authors: Duangkrayom Jaroon , Wang Shi-Qi , Deng Tao , Jintasakul Pratueng 
Published: December 2016

AbstractLower and upper third molars of a proboscidean from the Tha Chang sand pits, Nakhon Ratchasima, northeastern Thailand, show a zygodont pattern. The crescentoids are less well developed than those of the type specimen ofZygolophodon gobiensisbut similar to those of late Miocene specimens from south China assigned toZ.lufengensisandZ.chinjiensis. On the other hand, the loph(id)s are less oblique and the zygodont crests are less well developed than inZ.lufengensisandZ.chinjiensis. However, it is difficult to erect a new species for these specimens because their anterior loph(id)s are so deeply worn that the morphology of the conelets on these loph(id)s is unclear. Thus, we identify the specimens asZygolophodonsp.Zygolophodonis known from lower and middle Miocene sediments in Africa while they are usually dated to the early–late Miocene in Europe, South Asia such as Pakistan, and Central and North China. Based on its apparent grade of dental evolution, the new material ofZygolophodonfrom Thailand is probably late Miocene in age. In addition, this discovery is the first record of a zygodont proboscidean in Southeast Asia.
Impact of enriched environment on production of tau, amyloid precursor protein and, amyloid-β peptide in high-fat and high-sucrose-fed rats
Authors: Selvi Yavuz , Gergerlioglu Hasan Serdar , Akbaba Nursel , Oz Mehmet , Kandeger Ali , Demir Enver Ahmet , Yerlikaya Fatma Humeyra , Nurullahoglu-Atalik Kismet Esra 
Published: December 2016

ObjectiveThe Western-type diet is associated with an elevated risk of Alzheimer’s disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats.MethodsIn total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n=16) and standard housing condition (n=24). The groups were further divided into five subgroups that received standard diet, high-fat diet, and high-sucrose diet. We performed the analysis of amyloid β-peptide (Aβ) (1–40), Aβ(1–42), amyloid precursor protein (APP), and tau levels in the hippocampus of rats that were maintained under standard housing conditions or exposed to an EE.ResultsThe EE decreased the Aβ(1–40), Aβ(1–42), APP, and tau levels in high-fat and high-sucrose-fed rats.ConclusionThis observation shows that EE may rescue diet-induced amyloid and tau pathology.