bluuebunny/crossref_metadata_2025 huggingface dataset:
(E)-2-{[4-(Dimethylamino)benzylidene]amino}-5-nitrophenol
Authors: Hijji Yousef , Butcher Ray J. , Jasinski Jerry P.
Published: April 2014

The title Schiff base compound, C15H15N3O3, crystallizes with two molecules (AandB) in the asymmetric unit. Each molecule adopts anEconformation around the C= N imine bond. The two molecules have minor differences in their conformations. In moleculeA, the dihedral angle between the nitro group and its benzene ring is 2.1 (2)° and that between the two benzene rings is 0.88 (7)°, while the corresponding angles for moleculeBare 5.7 (1) and 2.45 (6)°, respectively. In each molecule, there is an intramolecular O—H...N hydrogen bond. In the crystal, inversion-related molecules are linkedviaO—H...O hydrogen bonds formingA–AandB–Bdimers. These dimers are linkedviaC—H...O hydrogen bonds involving the nitro O atoms, formingA–A–AandB–B–Bslabs that lie parallel to one another and to (010).
5-Amino-6-benzoyl-8-nitro-2,3-dihydro-1H-spiro[imidazo[1,2-a]pyridine-7,3′-indolin]-2′-one dimethyl sulfoxide monosolvate
Authors: Nagalakshmi R. A. , Suresh J. , Sivakumar S. , Kumar R. Ranjith , Lakshman P. L. Nilantha
Published: April 2014

In the title compound C21H17N5O4·C2H6OS, the central six-membered ring derived from 1,4-dihydropyridine adopts a distorted boat conformation with a small puckering amplitude of 0.127 (3) Å. The sums of bond angles around the pyridine N atom [358.7 (2)°] and the other imidazolidine N atom [60 (2)°] indicate that these atoms are insp2hybridization, leading to an essentially planar imidazolidine ring. The last heterocycle, an oxindole moiety, is also nearly planar with an r.m.s. deviation of 0.0185 (1) Å. The amine NH2group forms an intramolecular hydrogen bond with the benzoyl group, giving aS(6) motif. In the crystal, N—H...O hydrogen bonds lead to the formation of chains along thec-axis direction. Within the chains there are further N—H...O and C—H...O hydrogen bonds enclosingR22(14) ring motifs. The chains are linkedviaN—H...O and C—H...O hydrogen bonds involving the dimethyl sulfoxide solvent molecule which acts as both an acceptor and a donor..
4-Chloro-N′-[(E)-2-chlorobenzylidene]benzohydrazide monohydrate
Authors: Mague Joel T. , Mohamed Shaaban K. , Akkurt Mehmet , Potgieter Herman , Albayati Mustafa R.
Published: April 2014

The title compound, C14H10Cl2N2O·H2O, has a nearly planar extended conformation [C—N—N—C = −173.66 (15)°]. The dihedral angle between the aromatic rings is 4.6 (2)°. The water molecules alternate with benzohydrazide molecules in chains formed by O—H...O hydrogen bonds which run parallel to theaaxis. These chains are linked to neighboring chains through N—H...O and C—H...O interactions, forming a layer parallel to (001).
3-Bromo-2-[4-(methylsulfanyl)phenyl]-5,6,7,8-tetrahydro-1,3-benzothiazolo[3,2-a]imidazole
Authors: Bunev Alexander S. , Sukhonosova Elena V. , Statsyuk Vladimir E. , Ostapenko Gennady I. , Khrustalev Victor N.
Published: April 2014

In the title molecule, C16H15BrN2S2, the central imidazo[2,1-b]thiazole fragment is almost planar (r.m.s. deviation = 0.012 Å), and the fused 5,6,7,8-tetrahydrobenzene ring adopts an unsymmetrical half-chair conformation. The dihedral angle between the imidazo[2,1-b]thiazole and benzene planes is 18.25 (4)°. The terminal methylsulfanyl substituent lies practically within the benzene plane [the dihedral angle between the corresponding planes is 7.20 (10)°] and is turned toward the C—Br bond. In the crystal, molecules form infinite chains along [100]viasecondary Br...N interactions [3.1861 (16) Å]. The chains are arranged at van der Waals distances.
(R)-[(R)-3-Benzyl-2-oxooxazolidin-4-yl][4-(methylsulfonyl)phenyl]methyl acetate
Authors: Li Feng , Zhao Ming-Zhong , Jin Chun-Hua , Zou Jian-Wei
Published: April 2014

The structure of the title compound, C20H21NO6S, is of interest with respect to its antibacterial properties. The oxazolidine ring makes dihedral angles of 79.63 (14) and 56.16 (12)° with the phenyl and benzene rings, respectively, while the phenyl and benzene rings make a dihedral angle of 64.37 (13)°. In the crystal, non-classical C—H...O hydrogen bonds link adjacent molecules along thecaxis.
On the computation of diffraction peaks from discrete defects in continuous media: comparison of displacement and strain-based methods
Authors: Upadhyay Manas Vijay , Capolungo Laurent , Balogh Levente
Published: April 2014

This study introduces a numerical tool to generate virtual diffraction peaks from known elastic displacement or strain fields arising in the presence of discrete straight or curved dislocations in continuous media. The tool allows for the generation of diffraction peaks according to three methods: the displacement-based Fourier method of Warren, the Stokes–Wilson approximate method and a new average-strain-based Fourier method. The trade-off between the accuracy and the demand for computational power of the three methods is discussed. The work is applied to the cases of single-crystal microstructures containing (i) straight dislocations, (ii) low-angle symmetric tilt grain boundaries, (iii) a restrictedly random distribution of dislocations and (iv) complex microstructures generated by discrete dislocation dynamics, to illustrate the differences and domains of validity of the aforementioned methods. Dissimilar diffraction profiles reveal that peak broadening from dislocated crystals has additional contributions coming from strain gradients – a feature that is rejected in the Stokes–Wilson approximation. The problem of dealing with multi-valued displacement fields faced in the displacement-based Fourier method is overcome by the new average-strain-based Fourier method.
Form factor of cylindrical superstructures composed of globular particles
Authors: Chiappisi Leonardo , Prévost Sylvain , Gradzielski Michael
Published: April 2014

The scattering form factor arising fromNlinearly aligned particles, thereby forming a cylindrical superstructure and potentially contained within a cylindrical cage, has been derived. The principal features of the scattering curves are aq−1regime at mid-q(qis the magnitude of the scattering vector) due to the linear long-range order of the particles and, arising from the repetition of the building blocks, a correlation peak atq≃ 2π/D(Dbeing the center-to-center distance between the particles). In order to be able to describe real systems also, as they might arise in electrostatically assembled arrays, the effect of polydispersity of particle size and spacing has been evaluated. Finally, the model of aligned particles contained in a cylinder was applied to polyelectrolyte–surfactant complexes. It is shown that, provided thatNis sufficiently large, the scattering arising from aligned particles is clearly distinguishable from that of a homogeneous cylinder and therefore the presence of single particles within the complex can be demonstrated. The precise shape of the scattering curves then depends markedly on the contrast conditions between the contained particles, the cylindrical cage and the surrounding medium.
Lamella alignment ratio: a SAXS analysis technique for macromolecules
Authors: Dalton Eric , Collins Maurice N.
Published: April 2014

Polyethylenes with various morphologies were analysed, as a function of strain and radiation doses, using a novel lamella alignment ratio (LAR) technique on data obtained from small-angle X-ray scattering (SAXS) measurements at the Diamond Light Source synchrotron. The authors have used this technique previously to describe the influence of irradiation dose on crystal morphologies of orthopaedic grade polyethylenes. The aim of the current work is to highlight and explain the effectiveness of the LAR technique as an analysis tool for macromolecular crystal reorganization, crystallographic structural changes and crystal deformation during simultaneous strain measurements. Using new data for polyethylenes with varying morphology and irradiation dosage, the effectiveness of the technique is detailed. These findings are particularly useful for polymeric materials used in property critical applications and present a facile method for SAXS analysis. It is proposed that this method could potentially be used as a convenient route for the analysis of conditioning and crosslinking mechanisms on crystallographic relationships in more complex monomeric structures.
Intra-layer ordering and inter-layer disordering of the Li2MnO3phase in Li1.07Mn1.93O4–δcathode materials: electron diffraction investigation andDIFFaXsimulation of X-ray diffraction patterns
Authors: Zheng He , Wang Jianbo , Xu Zhongling , Gui Jianian
Published: April 2014

A previous transmission electron microscopy (TEM) analysis revealed the existence of monoclinic Li2MnO3in the lithium-rich and oxygen-deficient Li1.07Mn1.93O4−δpowder. Interestingly, the monoclinic phase exhibits different nanoscale lamellar variants involving a rotation of the stacking direction by 120 or 240° along the pseudo-threefold axis,i.e.the [103]M//[111]C(M and C denote the monoclinic and cubic phases, respectively) zone axis. Here, a theoretical X-ray diffraction (XRD) study of Li2MnO3employing theDIFFaXprogram is presented. It is found that, with the occurrence of different stacking configurations, the characteristic superstructure reflections with 2θ between 20 and 35° (Cu Kα) in the XRD pattern become more and more broadened with the increasing degree of stacking disorder, indicating that XRD may fall short in detecting the presence of the monoclinic Li2MnO3phase. Moreover, selective peak asymmetry appears when the stacking sequence becomes extremely disordered. Further selected-area electron diffraction and theoretical neutron diffraction investigation may clarify the similar ambiguity concerning the crystal phases of other structurally related compound cathode materials for lithium-ion batteries (e.g.LiNi1/2Mn1/2O2, LiNi1/3Co1/3Mn1/3O2).
Gestational diabetes mellitus and later cardiovascular disease: a Swedish population based case–control study
Authors: Fadl H , Magnuson A , Östlund I , Montgomery S , Hanson U , Schwarcz E
Published: April 2014

Objective

To identify if gestational diabetes mellitus (GDM) is a clinically useful marker of future cardiovascular disease (CVD) risk and if GDM combined with other risks (smoking, hypertension or body mass) identifies high‐risk groups.

Design

Population‐based matched case–control study.

Setting

National Swedish register data from 1991 to 2008.

Population

A total of 2639 women with a cardiovascular event and matched controls.

Methods

Conditional logistic regression examined associations with CVD before and after adjustment for conventional risk factors and confounders. Effect modification for the association of GDM with CVD by body mass index (BMI), smoking and chronic hypertension was assessed by stratification and interaction testing. Adjustment for diabetes post‐pregnancy evaluated its mediating role.

Main outcome measures

Inpatient diagnoses or causes of death identifying ischemic heart disease, ischemic stroke, atherosclerosis or peripheral vascular disease.

Results

The adjusted odds ratios (and 95% confidence intervals) for the association of CVD with GDM are 1.51 (1.07–2.14), 2.23 (2.01–2.48) for smoking, 1.98 (1.71–2.29) for obesity and 5.10 (3.18–8.18) for chronic hypertension. In stratified analysis the association of CVD with GDM was only seen among women with BMI ≥25, with an odds ratio of 2.39 (1.39–4.10), but only women with a BMI <30 accounted for this increased risk. Adjustment for post‐pregnancy diabetes attenuated it somewhat to 1.99 (1.13–3.52).

Conclusions

In the absence of other recognised cardiovascular risk factors, such as smoking, obesity or chronic hypertension, GDM is a useful marker of raised CVD risk among women with BMI between 25 and 29.
Complicated hepatic vein reconstruction in living donor liver transplantation: Case report and literature review
Authors: Shao Yi , Zhang Qiyi , Zhou Shuyang , Yan Sheng , Zhou Bo , Wang Weilin , Zhang Min , Shen Yan , Zheng Shusen
Published: April 2014

Hepatic vein reconstruction is one of the crucial issues in living donor liver transplantation (LDLT). In the present study, we report on a right liver LDLT excluding middle hepatic vein (MHV) using an MHV‐dominant graft. Two large‐sized inferior right hepatic veins were anastomosed to the recipient's inferior vena cava, respectively, in an end‐to‐side fashion. MHV tributaries were reconstructed using Y‐shaped cryopreserved iliac artery, but resulted in segment VIII congestion. A Fogarty catheter was then used to take out the thrombus and control the bleeding when anastomosis was being performed. The patient recovered uneventfully. Postoperative computed tomography showed patent interposition grafts and normal perfusion of the liver. The patient was doing well 13 months after transplantation.
Effects of food quality on trade‐offs among growth, immunity and survival in the greater wax mothGalleria mellonella
Authors: Krams Indrikis , Kecko Sanita , Kangassalo Katariina , Moore Fhionna R. , Jankevics Eriks , Inashkina Inna , Krama Tatjana , Lietuvietis Vilnis , Meija Laila , Rantala Markus J.
Published: April 2014

The resources available to an individual in any given environment are finite, and variation in life history traits reflect differential allocation of these resources to competing life functions. Nutritional quality of food is of particular importance in these life history decisions. In this study, we tested trade‐offs among growth, immunity and survival in 3 groups of greater wax moth (Galleria mellonella) larvae fed on diets of high and average nutritional quality. We found rapid growth and weak immunity (as measured by encapsulation response) in the larvae of the high‐energy food group. It took longer to develop on food of average nutritional quality. However, encapsulation response was stronger in this group. The larvae grew longer in the low‐energy food group, and had the strongest encapsulation response. We observed the highest survival rates in larvae of the low‐energy food group, while the highest mortality rates were observed in the high‐energy food group. A significant negative correlation between body mass and the strength of encapsulation response was found only in the high‐energy food group revealing significant competition between growth and immunity only at the highest rates of growth. The results of this study help to establish relationships between types of food, its nutritional value and life history traits ofG. mellonellalarvae.
Antibacterial Activity of Essential Oils of Edible Spices, Ocimum canum and Xylopia aethiopica
Authors: Vyry Wouatsa N. A. , Misra Laxminarain , Venkatesh Kumar R.
Published: April 2014

The essential oils of 2 Cameroonian spices, namely, Xylopia aethiopica and Ocimum canum, were chemically investigated and screened for their antibacterial activity. The essential oils were analyzed by means of GC, GC/MS, and NMR. X. aethiopica oil contained myrtenol (12%), a monoterpenoid in highest concentration. The essential oil of O. canum belonged to the known linalool (44%) rich chemotype. The results of the antibacterial screening against the food spoiling bacteria revealed a significant and broad spectrum of activity for these essential oils. The present material of X. aethiopica, which is having myrtenol in relatively higher concentration, has shown moderate antibacterial activity. The bioassay‐guided fractionation of Ocimum canum oil through flash chromatography showed that minor compounds, namely, α‐terpineol, chavicol, chavibetol, and trans‐p‐mentha‐2,8‐dien‐ol, significantly contributed for the overall activity observed. Hence, these results evidenced the possible potential of the essential oil of O. canum as a suitable antibacterial for controlling food‐borne pathogens whereas the X. aethiopica oil has moderate possibility.

Practical Application

There is a strong global demand for the microbe‐free, safe, and healthy foods. In this study, we showed that the essential oil of O. canum (wild basil) can be used as antibacterial for food items. Also, we showed that a value addition in the antibacterial potential of O. canum oil can be done by processing the essential oil through flash chromatographic separations.
Hairy cell leukemia presenting initially with symptoms of Behçet's disease
Authors: Oksuz Mustafa Ferhat , Coskun Belkis Nihan , Tufan Ayse Nur , Orucoglu Nurdan , Dalkilic Ediz , Öztürk Nazlıoğlu Hülya , Pehlivan Yavuz
Published: April 2014

Vasculitis is relatively uncommon in lymphoproliferative disease and may predate the diagnosis of lymphoproliferative disease. Many vasculitides have been associated with hairy cell leukemia (HCL), including polyarteritis nodosa (PAN) and leukocytoclastic vasculitis. We herein report a case whose initial presentation was like Behçet's disease (BD) (arthritis, oral and genital ulcerations, papulopustular skin lesions) in addition to pancytopenia, but turned out to have HCL. Because of the overlap between their symptoms, like oral ulcerations, skin lesions, arthritis and constitutional findings, HCL and BD may mimic each other. We should keep in mind other reasons for vasculitis such as lymphoproliferative disease, especially whose who have hematological abnormalities such as pancytopenia.
Field trial on removal of petroleum‐hydrocarbon pollutants using a microbial consortium for bioremediation and rhizoremediation
Authors: Pizarro‐Tobías Paloma , Niqui José L. , Roca Amalia , Solano Jennifer , Fernández Matilde , Bastida Felipe , García Carlos , Ramos Juan L.
Published: April 2014

Petroleum waste sludges are toxic and dangerous that is why environmental protection agencies have declared their treatment top priority. Physicochemical treatments are expensive and environmentally unfriendly, while alternative biological treatments are less costly but, in general, work at a slower pace. An in situ bioremediation and rhizoremediation field‐scale trial was performed in an area contaminated with oil refinery sludge under semiarid climate. The bioremediation and rhizoremediation treatments included the use of an artificial consortium made up of plant growth‐promoting rhizobacteria and polycyclic aromatic hydrocarbon‐degrading bacteria, and the combined use of the mentioned consortium along with pasture plants respectively. Rhizoremediation revealed that the development of vegetation favoured the evolution of indigenous microbiota with potential to remove petroleum wastes. This was inferred as the decline of total petroleum hydrocarbons 7 months after the biological treatment.
Nurse‐plant effects on the seed biology and germination of desert annuals
Authors: Sotomayor Diego A. , Lortie Christopher J. , Lamarque Laurent J.
Published: April 2014

Nurse‐plants generally have positive effects on understorey species by creating more suitable conditions for stress‐intolerant plants relative to open micro‐habitats. However, long‐term effects of this plant–plant facilitation system have been rarely examined. Seeds of five desert annual species from Atiquipa coastal desert in Southern Peru were used to examine whether different microenvironmental conditions under the nurse‐plants Caesalpinia spinosa Molina (Kuntze) lead to differences in seed biology and germinability of annual plants relative to open, canopy‐free conditions. Seeds collected from plants associated with nurse‐plants were predicted to be (i) larger due to more favourable growing conditions, (ii) more viable and with greater germination rates, (iii) less variable in size and viability due to reduced environmental heterogeneity, and (iv) to germinate faster to avoid apparent competition with other annuals. Seed attribute measurements and germination trials in growth chambers were used to test these predictions. Although the plant abundance of only 2 of 5 species was strongly facilitated by the nurse‐plant, no significant differences were found in seed mass, viability or relative variability between understorey and open micro‐habitats for any of the species. Contrary to our predictions, final seed germination rates of seeds from open micro‐habitats were higher, and the open micro‐habitat treatment was more favourable for germination of seeds from both open and understorey environments. Taken together, these results suggest that plant–plant facilitation does not necessarily affect seed biology traits. Further studies addressing larger distribution ranges and/or density gradients of understorey species will illuminate the potential evolutionary effects of nurse‐plants.
Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper
Authors: Pfaar O. , Demoly P. , Gerth van Wijk R. , Bonini S. , Bousquet J. , Canonica G. W. , Durham S. R. , Jacobsen L. , Malling H. J. , Mösges R. , Papadopoulos N. G. , Rak S. , Rodriguez del Rio P. , Valovirta E. , Wahn U. , Calderon M. A.
Published: April 2014

Background

Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune‐modifying and causal treatment available for patients suffering from IgE‐mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints.

Methods

As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis.

Results

Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed.

Conclusion

A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.
Governing the Commercial Streets of the City: New Terrains of Disinvestment and Gentrification in Toronto's Inner Suburbs
Authors: Rankin Katharine N. , McLean Heather
Published: April 2014

This paper explores the commercial shopping street as a site of racialized class struggle. The argument builds around the study of a disinvested inner‐suburban neighbourhood in Toronto, which furnishes an ideal case through which to achieve the paper's objectives of, first, identifying commercial space as an important site of contestation over competing suburban futures; second, delineating how processes of racialization inform the economies of commercial gentrification and urban renewal; and third, highlighting the epistemological and theoretical insights that emerge when research is conducted collaboratively, among academic, community, and activist groupings. The paper argues that such commercial spaces play a key role in making the city accessible to vulnerable and marginalized groups. Two competing planning agendas centred on reordering commercial space, meanwhile, spell the almost‐certain demise of such arrangements: a “real estate” vision featuring new condominium developments, and a new urbanist resistance favouring “green” and “creative” alternatives. Our engagements with precarious, predominantly immigrant‐owned businesses and community‐based researchers reveal the complicity of both modes of development planning with processes of displacement and structural racism. Specifying these dynamics as “racialized class projects” opens up space for intervention and organizing.
Disparity Despite Diversity: SocialInjustice in New York City's Urban Agriculture System
Authors: Reynolds Kristin
Published: April 2014

Many studies have documented the benefits of urban agriculture, including increased food access, job creation, educational opportunities, and green space. A focus on its social benefits has fed an association of urban agriculture with social justice, yet there is a distinction between alleviating symptoms of injustice (such as disparate access to food or environmental amenities) and disrupting structures that underlie them. Despite its positive impacts, urban agriculture systems may reinforce inequities that practitioners and supporters aim to address. This paper reports findings from a 2‐year study of urban agriculture in New York City, which found race‐ and class‐based disparities among practitioners citywide. Using the lens of critical race theory, it argues that a failure to examine urban agriculture's role in either supporting or dismantling unjust structures may perpetuate an inequitable system. The paper concludes with recommendations for urban agriculture supporters and scholars to help advance social justice at structural levels.
An Egyptian Partially Gilded Bronze Group Statue: Examination and Analysis
Authors: Ghoneim M.
Published: April 2014

This paper aims at examining and analysing an Egyptian partially gilded bronze group statue excavated from the San al‐hagar (Tanis) site and housed in the Egyptian Museum in Cairo in October 2007. It has deteriorated severely and is covered with an extremely disfiguring and heterogeneous crust that varies in colour, thickness and nature, and that is incorporated with soil particles in many parts. The gilding layer sandwiched between, under and above the corrosion products suffers from rupture, flaking and detachment. Examination and analysis were performed using optical microscopy (OM), an X‐ray diffractometer, equipped with an X‐ray fluorescence spectrometer (XRDF), and scanning electron microscopy, equipped with energy‐dispersive spectrometry (SEM–EDS). The study examined the nature and the chemical composition of the corrosion products, the body metal and the gilding layer. This study also discusses the corrosion phenomenon and the nature of the burial soil, and detects the decoration technology of the gilding.
An evaluation of inferential procedures for adaptive clinical trial designs with pre‐specified rules for modifying the sample size
Authors: Levin Gregory P. , Emerson Sarah C. , Emerson Scott S.
Published: April 2014

Many papers have introduced adaptive clinical trial methods that allow modifications to the sample size based on interim estimates of treatment effect. There has been extensive commentary on type I error control and efficiency considerations, but little research on estimation after an adaptive hypothesis test. We evaluate the reliability and precision of different inferential procedures in the presence of an adaptive design with pre‐specified rules for modifying the sampling plan. We extend group sequential orderings of the outcome space based on the stage at stopping, likelihood ratio statistic, and sample mean to the adaptive setting in order to compute median‐unbiased point estimates, exact confidence intervals, and P‐values uniformly distributed under the null hypothesis. The likelihood ratio ordering is found to average shorter confidence intervals and produce higher probabilities of P‐values below important thresholds than alternative approaches. The bias adjusted mean demonstrates the lowest mean squared error among candidate point estimates. A conditional error‐based approach in the literature has the benefit of being the only method that accommodates unplanned adaptations. We compare the performance of this and other methods in order to quantify the cost of failing to plan ahead in settings where adaptations could realistically be pre‐specified at the design stage. We find the cost to be meaningful for all designs and treatment effects considered, and to be substantial for designs frequently proposed in the literature.
A pathway EM‐algorithm for estimating vaccine efficacy with a non‐monotone validation set
Authors: Yang Yang , Halloran M. Elizabeth , Chen Yanjun , Kenah Eben
Published: April 2014

Here, we consider time‐to‐event data where individuals can experience two or more types of events that are not distinguishable from one another without further confirmation, perhaps by laboratory test. The event type of primary interest can occur only once. The other types of events can recur. If the type of a portion of the events is identified, this forms a validation set. However, even if a random sample of events are tested, confirmations can be missing nonmonotonically, creating uncertainty about whether an individual is still at risk for the event of interest. For example, in a study to estimate efficacy of an influenza vaccine, an individual may experience a sequence of symptomatic respiratory illnesses caused by various pathogens over the season. Often only a limited number of these episodes are confirmed in the laboratory to be influenza‐related or not. We propose two novel methods to estimate covariate effects in this survival setting, and subsequently vaccine efficacy. The first is a pathway expectation‐maximization (EM) algorithm that takes into account all pathways of event types in an individual compatible with that individual's test outcomes. The pathway EM iteratively estimates baseline hazards that are used to weight possible event types. The second method is a non‐iterative pathway piecewise validation method that does not estimate the baseline hazards. These methods are compared with a previous simpler method. Simulation studies suggest mean squared error is lower in the efficacy estimates when the baseline hazards are estimated, especially at higher hazard rates. We use the pathway EM‐algorithm to reevaluate the efficacy of a trivalent live‐attenuated influenza vaccine during the 2003–2004 influenza season in Temple‐Belton, Texas, and compare our results with a previously published analysis.
Cardiovascular event risk dynamics over time in older patients on dialysis: A generalized multiple‐index varying coefficient model approach
Authors: Estes Jason P. , Nguyen Danh V. , Dalrymple Lorien S. , Mu Yi , Şentürk Damla
Published: April 2014

Among patients on dialysis, cardiovascular disease and infection are leading causes of hospitalization and death. Although recent studies have found that the risk of cardiovascular events is higher after an infection‐related hospitalization, studies have not fully elucidated how the risk of cardiovascular events changes over time for patients on dialysis. In this work, we characterize the dynamics of cardiovascular event risk trajectories for patients on dialysis while conditioning on survival status via multiple time indices: (1) time since the start of dialysis, (2) time since the pivotal initial infection‐related hospitalization, and (3) the patient's age at the start of dialysis. This is achieved by using a new class of generalized multiple‐index varying coefficient (GM‐IVC) models. The proposed GM‐IVC models utilize a multiplicative structure and one‐dimensional varying coefficient functions along each time and age index to capture the cardiovascular risk dynamics before and after the initial infection‐related hospitalization among the dynamic cohort of survivors. We develop a two‐step estimation procedure for the GM‐IVC models based on local maximum likelihood. We report new insights on the dynamics of cardiovascular events risk using the United States Renal Data System database, which collects data on nearly all patients with end‐stage renal disease in the United States. Finally, simulation studies assess the performance of the proposed estimation procedures.
Nonpharmacologic Approaches for Pain Management During Labor Compared with Usual Care: A Meta‐Analysis
Authors: Chaillet Nils , Belaid Loubna , Crochetière Chantal , Roy Louise , Gagné Guy‐Paul , Moutquin Jean Marie , Rossignol Michel , Dugas Marylène , Wassef Maggy , Bonapace Julie
Published: April 2014

Objectives

To assess the effects of nonpharmacologic approaches to pain relief during labor, according to their endogenous mechanism of action, on obstetric interventions, maternal, and neonatal outcomes.

Data source

Cochrane library, Medline, Embase, CINAHL and the MRCT databases were used to screen studies from January 1990 to December 2012.

Study selection

According to Cochrane criteria, we selected randomized controlled trials that compared nonpharmacologic approaches for pain relief during labor to usual care, using intention‐to‐treat method.

Results

Nonpharmacologic approaches, based on Gate Control (water immersion, massage, ambulation, positions) and Diffuse Noxious Inhibitory Control (acupressure, acupuncture, electrical stimulation, water injections), are associated with a reduction in epidural analgesia and a higher maternal satisfaction with childbirth. When compared with nonpharmacologic approaches based on Central Nervous System Control (education, attention deviation, support), usual care is associated with increased odds of epidural OR 1.13 (95% CI 1.05–1.23), cesarean delivery OR 1.60 (95% CI 1.18–2.18), instrumental delivery OR 1.21 (95% CI 1.03–1.44), use of oxytocin OR 1.20 (95% CI 1.01–1.43), labor duration (29.7 min, 95% CI 4.5–54.8), and a lesser satisfaction with childbirth. Tailored nonpharmacologic approaches, based on continuous support, were the most effective for reducing obstetric interventions.

Conclusion

Nonpharmacologic approaches to relieve pain during labor, when used as a part of hospital pain relief strategies, provide significant benefits to women and their infants without causing additional harm.
A review of the management of childhood immune thrombocytopenia: how can we provide an evidence‐based approach?
Authors: Cooper Nichola
Published: April 2014

Most children with immune thrombocytopenia (ITP) have transiently low platelet counts and do not suffer from bleeding. Treatments with steroids, immunosuppression or splenectomy are not thought to be curative and may create more problems than the low platelet count. Consequently, many children do not receive treatment unless there is bleeding. However, although registry data looks promising, this approach outcome is not consistent between countries, or even between centres in the same country, leading to confusion for both physicians and families. Reaching a consensus for the management of paediatric ITP is further complicated by the lack of a diagnostic test and by the heterogeneity of the disease; for example, although most children remain relatively asymptomatic and go into an early remission, some patients have significant bleeding and others do not go into spontaneous remission. This review assesses the available evidence to guide physicians and families on making management decisions, showing the wide range of treatment choices, and the different approaches between countries and considers methods by which further information could be acquired to provide a more stratified approach to management.
The effects of social and health consequence framing on heavy drinking intentions among college students
Authors: Kingsbury John H. , Gibbons Frederick X. , Gerrard Meg
Published: April 2014

Objectives

Many interventions targeting college student drinking have focused on negative health effects of drinking heavily; however, some research suggests that social factors may have a stronger influence on the drinking behaviour of young people. Moreover, few studies have examined message framing effects in the context of alcohol consumption. This study investigated the effects of social and health consequence framing on college students' intentions to engage in heavy drinking.

Design

This study used a 2 × 2 experimental design with an appended control condition.

Methods

One hundred and twenty‐four college students (74 women; Mage = 18.9) participated in this study for course credit. Participants read vignettes that were ostensibly written by a recent graduate from the university, who described an episode of drinking in which he or she experienced either social or health consequences. These consequences were framed as either a gain (i.e., positive consequences of not drinking heavily) or a loss (i.e., negative consequences of drinking heavily). After reading the vignette, participants completed a measure of heavy drinking intentions.

Results

Regression analyses revealed that social consequences were associated with lower heavy drinking intentions when framed as a loss and that health consequences were associated with lower heavy drinking intentions when framed as a gain. These effects were stronger among those who reported higher (vs. lower) levels of previous drinking.

Conclusions

Results suggest that interventions that focus on the negative health effects of heavy drinking may be improved by instead emphasizing the negative social consequences of drinking heavily and the positive health consequences of avoiding this behaviour.

Statement of contribution

What is already known on this subject?

Previous studies have shown that gain frames are more effective than loss frames when highlighting the health consequences of health risk behaviours, such as heavy drinking. The heavy drinking behaviour of young people is influenced by social factors (e.g., perceived social consequences). However, little is known about framing effects for social consequences of heavy drinking.

What does this study add?

This study builds on previous research by demonstrating that a loss frame is more effective than a gain frame when highlighting the social consequences of health risk behaviour.

Framing effects are strongest for those with more previous drinking experience.
Indigenous Peasant ‘Otherness’: Rural Identities and Political Processes inBolivia
Authors: FONTANA LORENZA B.
Published: April 2014

SinceMorales's election, rural movements have become the new protagonists ofBolivian politics. Previous analyses have emphasised their active role in shaping national politics, often focusing on those organisations as a compact block. However, their relationship is marked by both cooperation and fragmentation. This article provides a narrative ofBolivian socio‐political history over the last 60 years, establishing four main phases of identitarian articulations/disarticulations. It demonstrates the high degree of interdependence and fluidity of ethnic and class identities, as well as their interconnections with the broader socio‐political context and the national legal and institutional changes.
Explaining Policy Outcomes in Federal Contexts: The Politics of Reproductive Rights in Argentina and Mexico
Authors: LOPREITE DEBORA
Published: April 2014

This article explains the political and institutional factors that affect reproductive rights policies in Argentina and Mexico. Consistent with the comparative literature on gender, politics and institutions, the article reveals that federal arrangements define the arenas in which advocates can challenge governments. The comparative analysis suggests that the content and variations of policy outcomes are not only determined by the legal distribution of such rights. Women's positions towards abortion and contraception was greatly shaped by partisanship and ideology, and this was critical to legislative outcomes, while the number of women legislators was only important to introduce the issues. Important for further research are the effects of institutional and party instability on women's organising in legislatures, and the relevance of links between women's groups outside legislature and political parties for the success of gender equality policies.
δ‐Opioid receptors in the accumbens shell mediate the influence of both excitatory and inhibitory predictions on choice
Authors: Laurent Vincent , Wong Felix L , Balleine Bernard W
Published: April 2014

Background and Purpose

Stimuli that predict rewarding events can control choice between future actions, and this control could be mediated by δ‐opioid receptors in the nucleus accumbens shell (NAc‐S). Stimuli predicting the absence of important events can also guide choice, although it remains unknown whether they do so via changes in an accumbal δ‐opioid receptor‐related process.

Experimental Approach

δ‐opioid receptor‐eGFP mice were trained to perform two instrumental actions that delivered different food outcomes. Choice between the two actions was then tested in the presence of stimuli paired with either the delivery or the non‐delivery of each of the two outcomes. Bilateral infusions of the δ‐opioid receptor antagonist naltrindole into the NAc‐S were used to determine the role of these receptors at the time of choice and δ‐opioid receptor expression in the NAc‐S used to assess functional activity.

Key Results

A stimulus predicting a specific outcome biased choice performance towards the action previously earning that same outcome. In contrast, a stimulus signalling the absence of that outcome biased performance away from the action that delivered that outcome towards actions associated with the absence of that outcome. Both effects were associated with increased δ‐opioid receptor expression on the membrane of cholinergic interneurons within the NAc‐S. Furthermore, both effects were blocked by naltrindole infused into the NAc‐S.

Conclusions and Implications

These findings suggest that δ‐opioid receptors in the NAc‐S were involved in the effects of predictive learning on choice between actions, whether those predictions involve the presence or absence of specific rewarding events.

Linked Articles

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Functional plasticity of the N/OFQ‐NOP receptor system determines analgesic properties of NOP receptor agonists
Authors: Schröder W , Lambert D G , Ko M C , Koch T
Published: April 2014

Despite high sequence similarity between NOP (nociceptin/orphanin FQ opioid peptide) and opioid receptors, marked differences in endogenous ligand selectivity, signal transduction, phosphorylation, desensitization, internalization and trafficking have been identified; underscoring the evolutionary difference between NOP and opioid receptors. Activation of NOP receptors affects nociceptive transmission in a site‐specific manner, with antinociceptive effects prevailing after peripheral and spinal activation, and pronociceptive effects after supraspinal activation in rodents. The net effect of systemically administered NOP receptor agonists on nociception is proposed to depend on the relative contribution of peripheral, spinal and supraspinal activation, and this may depend on experimental conditions. Functional expression and regulation of NOP receptors at peripheral and central sites of the nociceptive pathway exhibits a high degree of plasticity under conditions of neuropathic and inflammatory pain. In rodents, systemically administered NOP receptor agonists exerted antihypersensitive effects in models of neuropathic and inflammatory pain. However, they were largely ineffective in acute pain while concomitantly evoking severe motor side effects. In contrast, systemic administration of NOP receptor agonists to non‐human primates (NHPs) exerted potent and efficacious antinociception in the absence of motor and sedative side effects. The reason for this species difference with respect to antinociceptive efficacy and tolerability is not clear. Moreover, co‐activation of NOP and μ‐opioid peptide (MOP) receptors synergistically produced antinociception in NHPs. Hence, both selective NOP receptor as well as NOP/MOP receptor agonists may hold potential for clinical use as analgesics effective in conditions of acute and chronic pain.
Activation of GPR18 by cannabinoid compounds: a tale of biased agonism
Authors: Console‐Bram Linda , Brailoiu Eugen , Brailoiu Gabriela Cristina , Sharir Haleli , Abood Mary E
Published: April 2014

Background and Purpose

GPR18 is a candidate cannabinoid receptor, but its classification as such is controversial. The rationale of the study presented herein was to consider the effects of N‐arachidonoyl glycine (NAGly) and cannabinoids via differential G‐protein coupled pathways, in addition to β‐arrestin signalling. Cellular localization of GPR18 receptors was also examined.

Experimental Approach

Calcium mobilization and ERK1/2 phosphorylation were quantified in a cell line stably expressing GPR18 (HEK293/GPR18 cells). In addition, using the DiscoveRx PathHunter® CHO‐K1 GPR18 β‐arrestin cell line, recruitment of β‐arrestin was quantified.

Key Results

Concentration‐dependent increases in intracellular calcium and ERK1/2 phosphorylation were observed in the presence of NAGly, abnormal cannabidiol (AbnCBD), O‐1602, O‐1918 and Δ9‐tetrahydrocannabinol (Δ9‐THC) in HEK293/GPR18 cells. The initial rise in intracellular calcium in the presence of NAGly, O1918 and THC was blocked by either Gαq or Gαi/o inhibition. The ERK1/2 phosphorylation was inhibited by Pertussis toxin and N‐arachidonoyl‐L‐serine (NARAS). Recruitment of β‐arrestin in the PathHunter CHO‐K1 GPR18 cell line revealed a differential pattern of GPR18 activation; of all the ligands tested, only Δ9‐THC produced a concentration‐dependent response. The localization of GPR18 receptors within the HEK293/GPR18 cells is both intracellular, and on the plasma membrane.

Conclusions and Implications

These findings suggest that GPR18 activation involves several signal transduction pathways indicative of biased agonism, thereby providing a plausible explanation for the apparent discrepancies in GPR18 activation found in the literature. Additionally, the results presented herein provide further evidence for GPR18 as a candidate cannabinoid receptor.
Churg–Strauss syndrome: a new endotype of severe asthma? Results of 14 Turkish patients
Authors: Yılmaz İnsu , Çelik Gülfem , Aydın Ömür , Özdemir Seçil Kepil , Soyyiğit Şadan , Sözener Zeynep , Özgüçlü Selcan , Atasoy Çetin , Düzgün Nurşen , Mungan Dilşad , Sin Betül , Demirel Yavuz Selim , Mısırlıgil Zeynep
Published: April 2014

Introduction

Churg–Strauss syndrome (CSS) is a rare multisystem vasculitis. Considering the variation of autoimmune diseases in different races, it is of interest to determine whether any outstanding features exist for Turkish patients with CSS.

Objective

The aim of this study was to evaluate the clinical and serological features of the disease, the treatment, and long‐term follow‐up details, and to investigate possible etiological factors of Turkish CSS patients.

Methods

The study included 14 patients who were diagnosed with CSS, and followed by our department between 2004 and 2012. Possible etiological factors, initial symptoms, clinical presentations, treatment, as well as outcomes were documented. The study was approved by the local ethics.

Results

All patients fulfilled the American College of Rheumatology criteria. Initial symptoms were worsening asthma (n = 14; 100%) and skin lesions (n = 6; 43%). All patients had a diagnosis of asthma and nasal polyps, whereas 57.1% had aspirin hypersensitivity at the time of diagnosis. The lungs (100%) and skin (43%) were most commonly involved. Peripheral eosinophilia dominated on initial presentations of all patients. Initial treatments included oral methyl prednisolone in all cases, whereas cyclophosphamide and azathioprine were used in three cases. Relapses were detected in five cases. None of the cases were able to stop the oral corticosteroid treatment. No fatalities were observed.

Conclusion

We herein describe a new severe asthma endotype in connection with CSS. We suggest that physicians who deal with uncontrolled severe asthma cases should consider CSS in the presence of nasal polyps, aspirin hypersensitivity, and especially peripheral blood eosinophilia over 10%.