bluuebunny/crossref_metadata_2025 huggingface dataset:
Poly(N‐Isopropylacrylamide)‐Based Microgels and Their Assemblies for Organic‐Molecule Removal from Water
Authors: Parasuraman Deepika , Sarker Avijeet K. , Serpe Michael J.
Published: April 2012

We review our recent efforts utilizing poly(N‐isopropylacrylamide)‐co‐acrylic acid (pNIPAm‐co‐AAc) microgels and their assemblies for the removal of an azo‐dye molecule, 4‐(2‐Hyrodxy‐1‐napthylazo) benzenesulfonic acid sodium salt (Orange II), from aqueous solutions. First, the ability of dispersed, single microgels to remove Orange II from aqueous solutions at room temperature is discussed.1 Uptake efficiency (i.e., the amount of Orange II removed from water) increased with AAc composition in the microgels, yielding a maximum uptake efficiency of 29.5 % for pNIPAm microgels with 10 % AAc. Assemblies of microgels (aggregates) were also investigated for their removal efficiency, which yielded a maximum uptake efficiency of 44.1 % at room temperature.2 Removal efficiencies for the microgels and their aggregates were also monitored at elevated temperatures, and a maximum of 56.6 % removal efficiency was achieved for unaggregated microgels, while aggregates were able to remove 73.1 % Orange II. To further explore the impact of the microgel system’s structure on function, we investigated the role microgel size in the aggregates plays on the uptake efficiency. Initial observations showed that the aggregates composed of microgels with large diameter yielded improved uptake efficiency over the aggregates composed of small diameter microgels. Langmuir sorption isotherms were fit to the data for the dye removal by the unaggregated and aggregated microgels, which showed good fits in all cases.
Recent Developments in Atom Transfer Radical Polymerization (ATRP): Methods to Reduce Metal Catalyst Concentrations
Authors: Lou Qin , Shipp Devon A.
Published: April 2012

Atom transfer radical polymerization (ATRP) was initially developed in the mid‐1990s, and with continued refinement and use has led to significant discoveries in new materials. However, metal contamination of the polymer product is an issue that has proven detrimental to widespread industrial application of ATRP. The laboratories of K. Matyjaszewski have made significant progress towards removing this impediment, leading the development of “activators regenerated by electron transfer” ATRP (ARGET ATRP) and electrochemically mediated ATRP (eATRP) technologies. These variants of ATRP allow polymers to be produced with great molecular weight and functionality control but at significantly reduced catalyst concentrations, typically at parts per million levels. This Concept examines these polymerizations in terms of their mechanism and outcomes, and is aimed at giving the reader an overview of recent developments in the field of ATRP.
Blockade of Tim‐3 signaling restores the virus‐specific CD8+T‐cell response in patients with chronic hepatitis B
Authors: Wu Wei , Shi Yu , Li Shuping , Zhang Yun , Liu Yanning , Wu Yihua , Chen Zhi
Published: April 2012

Chronic hepatitis B (CHB) is characterized by functionally impaired virus‐specific CD8+ T‐cell responses. However, the mechanism underlying this dysfunction has not been fully clarified. We examined the role of a newly identified protein, T‐cell immunoglobulin domain and mucin domain‐containing molecule‐3 (Tim‐3), in regulating the antiviral CD8+ T‐cell response in CHB patients. Tim‐3 expression on peripheral virus‐specific CD8+ T cells from 20 CHB patients and 20 healthy controls was determined by flow cytometry. The phenotypes and cytokine‐producing capacity were compared between Tim‐3+CD8+ and Tim‐3−CD8+ T cells. The impact of Tim‐3 signaling on cellular proliferation and cytokine‐producing capacity was also studied. Tim‐3 expression on hepatitis B virus (HBV)‐specific CD8+ T cells was higher than expression on cytomegalovirus (CMV)‐specific CD8+ T cells. Tim‐3+ CD8+ T cells exhibited proliferative senescence phenotypes and decreased cytokine production upon antigen challenge. Finally, blocking the Tim‐3 pathway significantly improved proliferation and antiviral cytokine secretion of CD8+ T cells in response to HBV‐specific antigen peptides. Tim‐3 negatively regulates antiviral responses of CD8+ T cells isolated from CHB patients, and this response is reversed by blocking the Tim‐3 pathway.
Foxp3‐independent loss of regulatory CD4+T‐cell suppressive capacities induced by self‐deprivation
Authors: Delpoux Arnaud , Poitrasson‐Rivière Maud , Le Campion Armelle , Pommier Arnaud , Yakonowsky Philippe , Jacques Sébastien , Letourneur Franck , Randriamampita Clotilde , Lucas Bruno , Auffray Cédric
Published: April 2012

In the periphery, Foxp3 expression is considered sufficient to maintain natural regulatory CD4+ T‐cell suppressive function. In this study, we challenge this model. Indeed, in mouse chimeras in which major histocompatibility complex (MHC) class II expression is restricted to the thymus, peripheral regulatory CD4+ T cells lack suppressive activity. In addition, regulatory CD4+ T cells recovered 5 days after transfer into recipient mice lacking expression of MHC class II molecules (self‐deprived) are unable to inhibit the proliferative response of conventional CD4+ T cells both in vitro and in vivo. Disruption of TCR/MHC class II interactions rapidly leads to alterations in the regulatory CD4+ T‐cell phenotype, the ability to respond to stimulation and to produce interleukin‐10, and the transcriptional signature. Interestingly, self‐deprivation does not affect Foxp3 expression indicating that in regulatory CD4+ T cells, self‐recognition induces unique transcriptional and functional features that do not rely on Foxp3 expression.
From crucial to negligible: Functional CD8+T‐cell responses and their dependence on CD4+T‐cell help
Authors: Wiesel Melanie , Oxenius Annette
Published: April 2012

CD8+ T cells play an important role in controlling pathogenic infections and are therefore key players in the immune response. It has been shown that among other factors CD4+ T cells can shape the magnitude as well as the quality of primary and/or secondary CD8+ T‐cell responses. However, due to the complexity and the differences among diverse immunization or infection models, the overall requirement, the time points, as well as the specific mechanism(s) of CD4+ T‐cell help may differ substantially. Here, we summarize current knowledge about the differential requirement of CD4+ T‐cell help in promoting primary CD8+ T‐cell responses as well as establishing functional memory CD8+ T cells in various experimental settings.
IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate
Authors: Bernardo David , Vallejo‐Díez Sara , Mann Elizabeth R. , Al‐Hassi Hafid O. , Martínez‐Abad Beatriz , Montalvillo Enrique , Tee Cheng T. , Murugananthan Aravinth U. , Núñez Henar , Peake Simon T. C. , Hart Ailsa L. , Fernández‐Salazar Luis , Garrote Jose A. , Arranz Eduardo , Knight Stella C.
Published: April 2012

Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL‐13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL‐13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL‐6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin‐homing chemokine CCR8. These DCs did not have decreased T‐cell stimulatory capacity and primed T cells with the skin‐homing CLA molecule in an IL‐6‐dependent mechanism. Our results highlight the role of IL‐6 in UC and question the concept of UC as a Th2 disease and the relevance of IL‐13 in its etiology.
Type 2 innate lymphoid cells–new members of the “type 2 franchise” that mediate allergic airway inflammation
Authors: Mjösberg Jenny , Spits Hergen
Published: April 2012

Type 2 innate lymphoid cells (ILC2s) are members of an ILCfamily, which contains NKcells and Rorγt+ ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL‐17 and IL‐22. ILC2s are dedicated to the production of IL‐5 and IL‐13 and, as such, ILC2s provide an early and important source of type 2 cytokines critical for helminth expulsion in the gut. Several studies have also demonstrated a role for ILC2s in airway inflammation. In this issue of the European Journal of Immunology, Klein Wolterink et al. [Eur. J. Immunol. 2012. 42: 1106‐1116] show that ILC2s are instrumental in several models of experimental asthma where they significantly contribute to production of IL‐5 and IL‐13, key cytokines in airway inflammation. This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen‐specific inflammation in the airways as discussed in this commentary.
A Bombesin Copper Complex Based on a Bifunctional Cyclam Derivative
Authors: Liolios Christos C. , Zikos Christos , Fragogeorgi Eirini , Benaki Dimitra , Pelecanou Maria , Pirmettis Ioannis , Ioannidis Nikolaos , Sanakis Yiannis , Raptopoulou Catherine P. , Psycharis Vassilis , Terzis Aris , Boschetti Frédéric , Papadopoulos Minas S. , Sivolapenko Gregory , Varvarigou Alexandra D.
Published: April 2012

The reaction of the C‐functionalized cyclam chelating agent 1,4,8,11‐tetraazacyclotetradecane‐6‐carboxylic acid (1) with CuCl2 generated a stable and neutral complex 2, which was characterized by elemental analysis, UV/Vis and IR spectroscopy, electrospray ionization mass spectrometry (ESI‐MS), EPR spectroscopy and X‐ray crystallography. The secondary amine groups of 1 were protected to generate 3, which was further conjugated with the bombesin (BN) derivative H2N‐(Ornithine)3‐BN(2–14) by a solid phase peptide synthesis method. After cleavage from the resin and deprotection, the resulting product 5 was obtained and characterized with ESI‐MS and NMR spectroscopy, and was subsequently complexed under mild conditions with CuCl2 to generate complex 6 in high yield. Complex 6 was characterized with UV/Vis spectroscopy, ESI‐MS and EPR spectroscopy. The stability of complexes 2 and 6 was tested against cysteine, histidine and glutathione, and both complexes were found to be stable. The cyclam BN conjugate 5 and its CuII complex 6 were suitable for targeting the gastrin releasing peptide receptors (GRPrs) that are over expressed on PC‐3 cells. Both 5 and 6 showed high binding affinity to GRPrs during in vitro cell assays with human PC‐3 prostate cancer cells. The half maximal inhibitory concentration (IC50) values observed for 5 and 6 (0.30 ± 0.03 and 0.33 ± 0.03 nM, respectively) were similar to that of the [Tyr]4‐BN peptide (0.45 ± 0.04 nM), which was used as standard.
Vertical centrifugation of virgin olive oil under inert gas
Authors: Masella Piernicola , Parenti Alessandro , Spugnoli Paolo , Calamai Luca
Published: April 2012

Virgin olive oil vertical centrifugation under inert gas (IVC) was compared with conventional vertical centrifugation in contact with air (CVC). IVC gives a strong reduction of the oil oxygenation in terms of reduced dissolved oxygen concentration and oxidative indexes (peroxide values and K232). Minor compounds (chlorophyll and total phenols) and volatile compounds were not affected by the treatment.

Practical applications: A technical implementation of inertized vertical separators appears a practicable solution to preserve virgin olive oil quality traits. This can be easily implemented both by the mill owner with homemade adjustment of the existing machines and by plant industrial manufacturers.
Altering the scissile fatty acid binding site of Candida antarctica lipase A by protein engineering for the selective hydrolysis of medium chain fatty acids
Authors: Brundiek Henrike , Padhi Santosh Kumar , Kourist Robert , Evitt Andrew , Bornscheuer Uwe T.
Published: April 2012

Candida antarctica lipase A (CAL‐A) is the first representative of a new subclass of lipases because of its unique cap domain. The acyl‐binding tunnel – having a short alternative binding region – is mainly formed by this domain. In order to create CAL‐A variants with a high specificity for medium chain length (MCL) fatty acids (C6–C12), we used rational protein design to block the primary acyl‐binding tunnel of CAL‐A at position G237, which is near the junction to the alternative binding pocket. By closing the junction to the main tunnel, CAL‐A variants (G237A/L/V/Y) have been created, which are highly specific for medium chain fatty acids (MCFAs) as determined by chain length profiles with p‐nitrophenyl esters and triacylglycerides. Especially the CAL‐A variants G237L/V/Y, in which the junction to the primary tunnel is completely closed, show a distinct preference for the hydrolysis of hexanoate esters. Hydrolytic activity for substrates with a chain length >C6 is suppressed extensively in mutants G237L/V/Y. Therefore, these highly MCL specific CAL‐A variants may represent interesting biocatalysts for the production of MCL‐derived esters for the food, flavor, and fragrance industry.

Practical application: Since medium chain fatty acids (MCFAs: C6‐C10) and their corresponding triacylglycerides (MCTs) provide quick access to energy and have been considered to be less implicated in the accumulation of body fat than long chain fatty acids, they represent interesting food additives. As functional oils, they are part of weight loss diets or are used in clinical nutrition. In the food industry MCTs are also utilized as storage stabilizing agents in cooking products, as release agents in food processing or as flavor diluent. Another interesting field of application of MCFA derived compounds, especially of C6 esters and alcohols, is as ingredients in flavors and fragrances. The CAL‐A variants described in this study can be used for the biocatalytic synthesis of these compounds.
Evaluation of microalgal alternative jet fuel using the AHP method with an emphasis on the environmental and economic criteria
Authors: Haddad Mona , Fawaz Zouheir
Published: April 2012

The negative environmental impact of the aviation industry, related mainly to the gaseous emissions from turbine exhausts, is increasing with the increased demand on travel. In addition to the adverse environmental effects, the currently used aviation fuel is posing economic burdens on the air transport sector, with the increase in crude oil prices. Therefore, the aviation industry is investigating the potential of substituting the currently used aviation fuel with alternative fuels—mainly those derived from biofuels. Of all the available sources of biofuels, numerous studies indicate that those derived from algae seem to be the most promising, in terms of providing a viable and sustainable alternative to fossil fuels. This study explores the feasibility of microalgal jet fuel, taking into consideration technological, environmental, and economic aspects, using the analytic hierarchy process (AHP). Two scenarios are explored, with one stressing on the environmental importance and the second on the economic importance of the alternative jet fuel. The results indicate that microalgal derived jet fuel can only compete with conventional jet fuel, when giving the environmental criterion the higher weight. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 721–733, 2013
Double‐Blind Placebo‐Controlled Trial of Quetiapine in Anorexia Nervosa
Authors: Powers Pauline S. , Klabunde Megan , Kaye Walter
Published: April 2012

Objective

Our objective is to determine whether quetiapine was superior to placebo in increasing weight or reducing core symptoms of anorexia nervosa as assessed by the Yale–Brown–Cornell Eating Disorder Scale and the Eating Disorder Inventory‐2.

Method

Participants were randomised to 8 weeks of quetiapine or placebo.

Results

There are 21 participants who signed informed consent, 15 were randomised, 14 returned for at least one visit after receiving drug and 10 completed the study. There were no differences between drug and placebo in questionnaire scores, weight or measures of anxiety or depression.

Discussion

There was no difference between quetiapine and placebo on weight gain or core symptoms. Small effect sizes suggest that a higher number of participants would not increase significant differences between groups. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
A model for OFDM signals with applications
Authors: Kotzer Igal , Har‐Nevo Smadar , Sodin Sasha , Litsyn Simon
Published: April 2012

A novel model for constant energy constellation (the data is drawn from equi‐energy symbols) discrete time orthogonal frequency‐division multiplexing (OFDM) signal is presented. On the basis of this model, the moments of the OFDM signal's envelope maximum and the moments of the energy of the clipped portion of the signal are computed. It is also shown that the rate at which the expected value of the maximum scales with the length of the signal coincides with Halasz's result. Simulations are presented, which show that this model gives much better results than the conventional Gaussian model in approximation of statistical properties of an OFDM signal. Copyright © 2012 John Wiley & Sons, Ltd.
Spatial and Temporal Pattern of Caddisfly Distribution at a Mesohabitat Scale in two Patagonian Mountain Streams Subjected to Pastoral Use
Authors: Brand Cecilia , Miserendino María Laura , Epele Luis B.
Published: April 2012

Substrate, flow type, nutrients, aquatic vegetation, organic matter, and caddisfly community structure were studied at two low order streams (Glyn and Nant y Fall) subjected to pastoral use in the Patagonian mountains. At both sites, we examined the effect of habitat type (boulder‐pebble with and without filamentous algae, cobble‐pebble, gravel‐sand, leaf‐pack, the submerged macrophytes Myriophyllum quitense and Isoetes savatieri) and season (high and low water period) on caddisfly assemblages. Benthic particulate organic matter (BPOM) ranged between 4.6 and 472 g m–2, all allochtonous detrital fractions were significantly higher at leaf‐packs at Glyn, whereas M. quitense habitats supported more BPOM and macrophytes biomass at Nant y Fall. As expected, boulder‐pebble sustained higher Trichoptera richness than M. quitense and gravel‐sand, moreover all habitats showed higher density than M. quitense at Nant y Fall. According to our results at least nine caddisfly species exhibited some habitat preference with boulder‐pebble and cobble‐pebble the most selected habitat. These particular habitats sustained more than 68% of the total caddisfly species. Multidimensional scaling ordination highlighted differences in composition per habitat for both sites showing a clear distinction among depositional and erosional habitats. Substrate, flow type, detritus biomass were important predictors defining assemblages. Based upon our findings, those anthropogenic actions or stressors that change hydraulic as well substrate attributes in mountain streams such as stock trampling, dredging, clearing of riparian areas, will reduce caddisfly richness. These results are relevant for outline management and conservation biomonitoring and schemes in headwater Patagonian streams as well as other similar environments worldwide (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Experimental Assessment of the Effects of Environmental Factors and Longitudinal Position on Alpha and Beta Diversities of Aquatic Insects in a Neotropical Stream
Authors: Hepp Luiz U. , Landeiro Victor L. , Melo Adriano S.
Published: April 2012

We evaluated the effect of environmental factors on the abundance and genera richness of aquatic insects colonizing artificial substrates. We also assessed the relative effects of environmental factors on assemblage variation (beta diversity), and contrasted its magnitude with the variation associated with the spatial position of reaches in a Neotropical stream. Homogeneous and heterogeneous bricks were installed in seven stream reaches and removed after 60d. Substrate type and organic matter showed significant effects on abundance. For observed richness, substrate type was the only important variable. For rarefied richness, no explanatory variable was important. A NMDS ordination of bricks revealed the effect of spatial position and substrate type. A partial Redundancy Analysis (pRDA) indicated that the environmental matrix explained 12.44% of the total variation, while reach position explained 7.41%. We conclude that at local scale (reaches 430–920 m apart), environmental factors, especially substrate heterogeneity, were important in determining the alpha and beta diversities of the insect assemblage in the stream (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Calf thymus DNA binding studies of the new neodymium–naproxen complex
Authors: Huo Ruina , Xu Guiqing , Jiang Xiaoying , Ge Yao , Xue Zaikun , Cui Fengling
Published: April 2012

Fluorescence spectroscopy in combination with UV absorption spectroscopy was carried out to investigate the interaction between the neodymium–naproxen complex (Nd–NAP) and calf thymus DNA (ctDNA). The experimental results showed that Nd–NAP intercalated with the ctDNA base pairs. Analysis of fluorescence quenching data of Nd–NAP by ctDNA at different temperatures using a Stern–Volmer equation revealed that dynamic and static quenching occurred simultaneously. The binding constants and the number of binding sites at 293 and 310 K were obtained as 2.904 × 104 L mol−1, 1.172 and 2.432 × 104 L mol−1, 1.143, respectively. The thermodynamic parameters ΔG, ΔH, and ΔS calculated at different temperatures indicated that hydrogen bonding and van der Waals force were the main binding forces. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:193–198, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21401
Experimental Analysis of Perching in the European Starling (Sturnus vulgaris: Passeriformes; Passeres), and the Automatic Perching Mechanism of Birds
Authors: GALTON PETER M. , SHEPHERD JEFFREY D.
Published: April 2012

The avian automatic perching mechanism (APM) involves the automatic digital flexor mechanism (ADFM) and the digital tendon‐locking mechanism (DTLM). When birds squat on a perch to sleep, the increased tendon travel distance due to flexion of the knee and ankle supposedly causes the toes to grip the perch (ADFM) and engage the DTLM so perching while sleeping involves no muscular effort. However, the knees and ankles of sleeping European starlings (Sturnus vulgaris) are only slightly flexed and, except for occasional balancing adjustments, the distal two‐thirds of the toes are not flexed to grip a 6‐mm‐diameter perch. The cranial ankle angle (CAA) is ∼120° and the foot forms an inverted “U” that, with the mostly unflexed toes, provides a saddle‐like structure so the bird balances its weight over the central pad of the foot (during day weight further back and digits actively grasp perch). In the region of the pad, the tendon sheath of many birds is unribbed, or only very slightly so, and it is always separated from the tendon of the M. flexor digitorum longus by tendons of the other toe flexor muscles. Passive leg flexion produces no toe flexion in anesthetized Starlings and only after 15–20 min, at the onset of rigor mortis, in freshly sacrificed Starlings. Anesthetized Starlings could not remain perched upon becoming unconscious (ADFM, DTLM intact). Birds whose digital flexor tendons were severed or the locking mechanism eliminated surgically (no ADFM or DTLM), so without ability to flex their toes, slept on the perch in a manner similar to unoperated Starlings (except CAA ∼90°–110°). Consequently, there is no APM or ADFM and the DTLM, although involved in lots of other activities, only acts in perching with active contraction of the digital flexor muscles. J. Exp. Zool. (c) Wiley‐Liss, Inc. How to cite this article: Galton PM, Shepherd JD. 2010. Experimental analysis of perching in the European starling (Sturnus vulgaris: Passeriformes; Passeres), and the automatic perching mechanism of birds. J. Exp. Zool. 317:205–215, 2012. © 2012 Wiley Periodicals, Inc.
Hepatocyte growth factor overexpression in the nervous system enhances learning and memory performance in mice
Authors: Kato Takashi , Funakoshi Hiroshi , Kadoyama Keiichi , Noma Satsuki , Kanai Masaaki , Ohya‐Shimada Wakana , Mizuno Shinya , Doe Nobutaka , Taniguchi Taizo , Nakamura Toshikazu
Published: April 2012

Hepatocyte growth factor (HGF) and its receptor, c‐Met, play pivotal roles in the nervous system during development and in disease states. However, the physiological roles of HGF in the adult brain are not well understood. In the present study, to assess its role in learning and memory function, we used transgenic mice that overexpress HGF in a neuron‐specific manner (HGF‐Tg) to deliver HGF into the brain without injury. HGF‐Tg mice displayed increased alternation rates in the Y‐maze test compared with age‐matched wild‐type (WT) controls. In the Morris water maze (MWM) test, HGF‐Tg mice took less time to find the platform on the first day, whereas the latency to escape to the hidden platform was decreased over training days compared with WT mice. A transfer test revealed that the incidence of arrival at the exact location of the platform was higher for HGF‐Tg mice compared with WT mice. These results demonstrate that overexpression of HGF leads to an enhancement of both short‐ and long‐term memory. Western blot analyses revealed that the levels of N‐methyl‐D‐aspartate (NMDA) receptor subunits NR2A and NR2B, but not NR1, were increased in the hippocampus of HGF‐Tg mice compared with WT controls, suggesting that an upregulation of NR2A and NR2B could represent one mechanism by which HGF enhances learning and memory performance. These results demonstrate that modulation of learning and memory performance is an important physiological function of HGF that contributes to normal CNS plasticity, and we propose HGF as a novel regulator of higher brain functions. © 2012 Wiley Periodicals, Inc.
The value of developing frontline leaders in health care
Authors: Ohnmacht Susan D.
Published: April 2012

The complexity of today's health care environment requires leaders to develop a coordinated strategy to promote organizational sustainability and maintain a competitive advantage in the workplace. Strong leaders provide the backbone for successful organizations (Patterson, 2009; Squazzo, 2009). A leadership preparedness strategy focused on the development of future leaders facilitates a seamless leadership transition when planned or unexpected turnover occurs (Carriere, Muise, Cummings, & Newburn‐Cook, 2009; Jones, 2010; Squazzo, 2009). The challenge faced by executive health care leaders is the ability to manage talent effectively and meet the strategic business objectives of the health care organization by building a talent pool of future leaders (Silzer & Church, 2009). Experiential learning and relationship learning support the professional growth and development of frontline leaders. One example of a structured program, blending experiential and relationship learning for developing high potentials, is the Frontline Nursing Leadership (FNLP) program, developed and facilitated by The Advisory Board Company (TABC; 2009). Health care organizations have a responsibility to cultivate tomorrow's leaders by mitigating and neutralizing barriers to professional development and establishing a comprehensive framework for the development of high‐potential employees (Squazzo, 2009).
Injection Moulding Difficult Nanopatterns with Hybrid Polymer Inlays
Authors: Stormonth‐Darling John M. , Gadegaard Nikolaj
Published: April 2012

Hybrid polymeric inlays, patterned by nanoimprint lithography, are used to rapidly mass replicate pillar‐like nanostructures by injection moulding. This is difficult to achieve with traditional nickel inlays due to the rapid heat transfer of the metal, which results in premature cooling of the molten polymer and improper filling of nanoscale features. Using hybrid inlays, nanopillars can reliably be stretched by up to 40% of their designed height by adjusting moulding parameters. Hybrid inlays display longevity of more than 2000 cycles and can rapidly be fabricated to firmly establish injection moulding as an exceptionally useful tool for the high volume prototyping and production of nanopatterned polymeric devices.

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On the super‐restricted arc‐connectivity of s ‐geodetic digraphs
Authors: Balbuena Camino , García‐Vázquez Pedro , Hansberg Adriana , Montejano Luis Pedro
Published: April 2012

For a strongly connected digraph D the restricted arc‐connectivity λ′(D) is defined as the minimum cardinality of an arc‐cut over all arc‐cuts S satisfying that D ‐ S has a non‐trivial strong component D1 such that D ‐ V (D1) contains an arc. In this paper we prove that every digraph on at least 4 vertices and of minimum degree at least 2 is λ′ ‐connected and λ′(D) ≤ξ′(D), where ξ′(D) is the minimum arc‐degree of D. Also in this paper we introduce the concept of super‐ λ′ digraphs and provide a sufficient condition for an s ‐geodetic digraph to be super‐ λ′. Further, we show that the h ‐iterated line digraph Lh(D) of an s ‐geodetic digraph is super‐ λ′ for a particular h. © 2012 Wiley Periodicals, Inc. NETWORKS, 2013
Connectedness of finite distance graphs
Authors: Gómez‐Pérez Domingo , Gutierrez Jaime , Ibeas Álvar
Published: April 2012

We describe a polynomial‐time algorithm for deciding whether a given distance graph with a finite number of vertices is connected. This problem was conjectured to be NP‐hard in Draque Penso et al. © 2012 Wiley Periodicals, Inc. NETWORKS, 2012
Shear‐flexible subdivision shells
Authors: Long Quan , Burkhard Bornemann P. , Cirak Fehmi
Published: April 2012

We present a new shell model and an accompanying discretisation scheme that is suitable for thin and thick shells. The deformed configuration of the shell is parameterised using the mid‐surface position vector and an additional shear vector for describing the out‐of‐plane shear deformations. In the limit of vanishing thickness, the shear vector is identically zero and the Kirchhoff–Love model is recovered. Importantly, there are no compatibility constraints to be satisfied by the shape functions used for discretising the mid‐surface and the shear vector. The mid‐surface has to be interpolated with smooth C1‐continuous shape functions, whereas the shear vector can be interpolated with C0‐continuous shape functions. In the present paper, the mid‐surface as well as the shear vector are interpolated with smooth subdivision shape functions. The resulting finite elements are suitable for thin and thick shells and do not exhibit shear locking. The good performance of the proposed formulation is demonstrated with a number of linear and geometrically non‐linear plate and shell examples. Copyright © 2012 John Wiley & Sons, Ltd.
Health‐related quality of life in sickle cell disease: Past, present, and future
Authors: Panepinto Julie A. , Bonner Melanie
Published: April 2012

Health‐related quality of life (HRQL) is defined as the patient's appraisal of how his/her well being and level of functioning, compared to the perceived ideal, are affected by individual health. The study of HRQL in children and adults with sickle cell disease (SCD) has begun to flourish. Given the devastating complications of the disease and other co‐morbid factors patients experience that influence HRQL, it is increasingly important to understand HRQL. The focus of this critical review was to examine past and current research in HRQL in SCD where a validated instrument was used. In addition, future directions for HRQL in SCD are explored. Pediatr Blood Cancer 2012;59:377–385. © 2012 Wiley Periodicals, Inc.
The medical home experience among children with sickle cell disease
Authors: Raphael Jean L. , Rattler Tiffany L. , Kowalkowski Marc A. , Mueller Brigitta U. , Giordano Thomas P.
Published: April 2012

Background

While a large body of research documents acute care services for children with sickle cell disease (SCD), little is known about the primary care experiences of this population. The goal of this study was to determine to what extent children with SCD experienced care consistent with a patient‐centered medical home (PCMH).

Procedure

We collected and analyzed data from 150 children, ages 1–17 years, who received care within a large children's hospital. The primary dependent variable was access to a PCMH or its four individual components (regular provider, comprehensive care, family‐centered care, and coordinated care) as determined by parental report. Multivariate logistic regression was conducted to investigate associations between socio‐demographic variables and having access to a PCMH.

Results

Only 11% (16/150) of children qualified as having a PCMH, achieving the required thresholds in all four components. Approximately half of children had access to two or fewer components. Over 90% of children were reported to have a personal provider. Two‐thirds of children had access to comprehensive care. Almost 60% of children were reported to receive family‐centered care. Only 20% of children had access to coordinated care. No consistent associations were found between socio‐demographic variables and having access to a PCMH or its individual components.

Conclusions

Within our study sample, children with SCD experienced multiple deficiencies in having access to a PCMH, particularly with respect to care coordination. However, further studies with larger samples are needed to determine associations between socio‐demographic variables and having a PCMH. Pediatr Blood Cancer 2013;60:275–280. © 2012 Wiley Periodicals, Inc.
Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods
Authors: Choi Sung W. , Chang Lawrence , Hanauer David A. , Shaffer‐Hartman Jacqueline , Teitelbaum Daniel , Lewis Ian , Blackwood Alex , Akcasu Nur , Steel Janell , Christensen Joy , Niedner Matthew F.
Published: April 2012

Background

Pediatric hematology–oncology (PHO) patients are at significant risk for developing central line‐associated bloodstream infections (CLA‐BSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospital‐acquired CLA‐BSIs.

Materials and Methods

CLA‐BSI rates were analyzed within a single‐institution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using time‐series methods to evaluate the pre‐ and post‐intervention effect of the practice changes.

Results

The pre‐intervention CLA‐BSI incidence was 2.92 per 1,000‐patient days (PD) and coagulase‐negative Staphylococcus was the most prevalent pathogen (29%). In the post‐intervention period, the CLA‐BSI rate decreased substantially (45%) to 1.61 per 1,000‐PD (P < 0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLA‐BSI rate compared to non‐BMT patients (P < 0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLA‐BSI rate reduction such that BMT and non‐BMT CLA‐BSI rates were not significantly different post‐intervention.

Conclusions

By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLA‐BSI incidence in our study population was significantly reduced and maintained. Pediatr Blood Cancer 2013;60:262–269. © 2012 Wiley Periodicals, Inc.
Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab
Authors: Marsh Rebecca A. , Allen Carl E. , McClain Kenneth L. , Weinstein Joanna L. , Kanter Julie , Skiles Jodi , Lee Nadine D. , Khan Shakila P. , Lawrence Julia , Mo Jun Q. , Bleesing Jack J. , Filipovich Alexandra H. , Jordan Michael B.
Published: April 2012

Background

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that remains difficult to treat. Even with current standard HLH therapy, only approximately half of patients will experience complete resolution of disease, and early mortality remains a significant problem. Salvage therapies have been described only in limited case reports, and there are no large studies of second‐line therapies.

Procedure

We reviewed the charts of 22 pediatric and adult patients who received alemtuzumab for the treatment of refractory HLH at our center or in consultation with our group.

Results

Patients had received conventional therapies for a median of 8 weeks (range: 2–70) prior to alemtuzumab, and treatment immediately prior to alemtuzumab included dexamethasone (100%), etoposide (77%), cyclosporine (36%), intrathecal hydrocortisone ± methotrexate (23%), methylprednisolone (9%), and rituximab (14%). Patients received a median dose of 1 mg/kg alemtuzumab (range: 0.1–8.9 mg/kg) divided over a median of 4 days (range: 2–10). Fourteen patients experienced an overall partial response, defined as at least a 25% improvement in two or more quantifiable symptoms or laboratory markers of HLH 2 weeks following alemtuzumab (64%). Five additional patients had a 25% or greater improvement in a single quantifiable symptom or laboratory marker of HLH (23%). Seventy‐seven percent of patients survived to undergo allogeneic hematopoietic cell transplantation. Patients experienced an acceptable spectrum of complications, including CMV and adenovirus viremia.

Conclusion

Alemtuzumab appears to be an effective salvage agent for refractory HLH, leading to improvement and survival to HCT in many patients. Prospective trials to define optimal dosing levels, schedules, and responses are needed. Pediatr Blood Cancer 2013; 60: 101–109. © 2012 Wiley Periodicals, Inc.
Shared medical decision‐making: considering what options to present based on an ethical analysis of the treatment of brain tumors in very young children
Authors: Levine Deena , Cohen Kenneth , Wendler David
Published: April 2012

The treatment of brain tumors in very young children poses both a therapeutic challenge and a bioethical quandary. The administration of craniospinal radiation after surgery offers the greatest chance for cure but causes severe neurocognitive damage. As a result, current practice does not offer parents the option of full‐dose postoperative craniospinal radiation. Some may regard this approach as inappropriate medical paternalism, while others may consider it an example of responsible therapeutics. Evaluation of this dilemma reveals principles which can guide clinicians in determining which treatment options to present to their patients or surrogates, in the context of shared medical decision‐making. Pediatr Blood Cancer 2012;59:216–220. © 2012 Wiley Periodicals, Inc.
Immunoproteomics of Brucella abortus reveals differential antibody profiles between S19‐vaccinated and naturally infected cattle
Authors: Pajuaba Ana C. A. M. , Silva Deise A. O. , Almeida Karine C. , Cunha‐Junior Jair P. , Pirovani Carlos P. , Camillo Luciana R. , Mineo José R.
Published: April 2012

Brucella abortus is a Gram‐negative intracellular bacterium that causes infectious abortion in food‐producing animals and chronic infection in humans. This study aimed to characterize a B. abortus S19 antigen preparation obtained by Triton X‐114 (TX‐114) extraction through immunoproteomics to differentiate infected from vaccinated cattle. Three groups of bovine sera were studied: GI, 30 naturally infected cows; GII, 30 S19‐vaccinated heifers; and GIII, 30 nonvaccinated seronegative cows. One‐dimensional (1D) and two‐dimensional electrophoretic profiles of TX‐114 hydrophilic phase antigen revealed a broad spectrum of polypeptides (10–79 kDa). 1D immunoblot showed widespread seroreactivity profile in GI compared with restricted profile in GII. Three antigenic components (10, 12, 17 kDa) were recognized exclusively by GI sera, representing potential markers of infection and excluding vaccinal response. The proteomic characterization revealed 56 protein spots, 27 of which were antigenic spots showing differential seroreactivity profile between GI and GII, especially polypeptides <20 kDa that were recognized exclusively by GI. MS/MS analysis identified five B. abortus S19 proteins (Invasion protein B, Sod, Dps, Ndk, and Bfr), which were related with antigenicity in naturally infected cattle. In conclusion, immunoproteomics of this new antigen preparation enabled the characterization of proteins that could be used as tools to develop sensitive and specific immunoassays for serodiagnosis of bovine brucellosis, with emphasis on differentiation between S19 vaccinated and infected cattle.
Mechanism for the reactions of sulfides and sulfoxides with hypochlorites: racemization and oxygen exchange of oxysulfonium salts and sulfoxides
Authors: Ruff Ferenc , Jalsovszky István , Szabó Dénes , Rábai József , Farkas Ödön , Kucsman Árpád
Published: April 2012

Density functional theory computations have been performed on the oxidations of sulfides and sulfoxides with hypochlorite ion (OCl−), hypochlorous acid, and alkyl hypochlorites to study the mechanism of the reactions. The OCl− anion transforms sulfides to sulfoxides and sulfoxides to sulfones in oxygen transfers. The oxygen atom of QOCl hypochlorites (Q = H, Me, t‐Bu) attacks at the sulfur atom of the substrates, and oxysulfonium cation intermediates are formed; the departure of the leaving Cl− is catalyzed by soft Lewis acids. The structures of the early transition states are determined by highest occupied molecular orbital–lowest unoccupied molecular orbital interactions. The sulfur compounds are the electron acceptors in the reaction with OCl−, but they are the electron donors in the reactions with QOCl. The attack of Cl− at the oxygen atom of oxysulfonium cation intermediates leads to the sulfide and QOCl precursors and can result in racemization, oxygen exchange, and reduction of oxysulfonium salts in reversible reactions. The attack of Cl− at the sulfur atom of oxysulfonium salts produces λ4‐sulfane intermediates. Oxysulfonium cations can be transformed into sulfoxide products with the attack of Cl− or water at the α‐carbon atom of the O‐alkyl group. The attack of water at the sulfur atom of oxysulfonium cation leads to hydrolysis or oxygen exchange reactions. Racemization and oxygen exchange of sulfoxides proceeds in similar reactions, through the formation of hydroxysulfonium cation intermediates in acidic media in the presence of Cl−. Chlorosulfonium cations are of very high energy; their intermediacy can be ruled out in the reactions of sulfides with hypochlorites. Copyright © 2012 John Wiley & Sons, Ltd.
Brodifacoum is effective against Norway rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance in Westphalia, Germany
Authors: Buckle Alan P , Klemann Nicole , Prescott Colin V
Published: April 2012

BACKGROUND:The tyrosine to cysteine amino acid substitution at location 139 of thevkorc1protein (i.e. tyrosine139cysteine or Y139C) is the most widespread anticoagulant resistance mutation in Norway rats (Rattus norvegicusBerk.) in Europe. Field trials were conducted to determine the incidence of the Y139C mutation at two rat‐infested farms in Westphalia, Germany, and to estimate the practical efficacy against them of applications, using a pulsed baiting treatment regime, of a proprietary bait (Klerat™) containing 0.005% brodifacoum.

RESULTS:DNA analysis for the Y139C mutation showed that resistant rats were prevalent at the two farms, with an incidence of 80.0 and 78.6% respectively. Applications of brodifacoum bait achieved results of 99.2 and 100.0% control at the two farms, when measured by census baiting, although the treatment was somewhat prolonged at one site, possibly owing to the abundance of attractive alternative food.

CONCLUSION:The study showed that 0.005% brodifacoum bait is fully effective against Norway rats possessing the Y139C mutation at the Münsterland focus and is likely to be so elsewhere in Europe where this mutation is found. The pulsed baiting regime reduced to relatively low levels the quantity of bait required to control these two substantial resistant Norway rat infestations. Previous studies had shown much larger quantities of bromadiolone and difenacoum baits used in largely ineffective treatments against Y139C resistant rats in the Münsterland. These results should be considered when making decisions about the use of anticoagulants against resistant Norway rats and their potential environmental impacts. Copyright © 2012 Society of Chemical Industry
Concise guide to today's management of hypertension
Authors: Ball Stephen , Berkin Liz
Published: April 2012

Our Drug review of hypertension provides an overview of the latest NICE guidance on hypertension and gives a straightforward approach to management using the wide range of effective drugs available. Copyright © 2012 Wiley Interface Ltd
Hypercholesterolaemia: what to do when first‐line treatment fails
Authors: Durrington Paul
Published: April 2012

Our series on Prescribing challenges focusses on areas of therapeutics that can present a particular challenge in general practice. Here, Professor Durrington considers the options available when target LDL cholesterol levels are not reached with simvastatin 40mg daily or it is not tolerated. Copyright © 2012 Wiley Interface Ltd
A multi‐scale approach to determine accurate elemental and isotopic ratios by nano‐scale secondary ion mass spectrometry imaging
Authors: Hatton Pierre‐Joseph , Remusat Laurent , Zeller Bernd , Derrien Delphine
Published: April 2012

RATIONALE

Nano‐scale secondary ion mass spectrometry (NanoSIMS) is still hampered by a lack of appropriate calibration method for the quantification of elemental and isotopic ratios in heterogeneous materials such as soil samples. The potential of 13C‐15N‐labeled density fractions of soil to calibrate the C/N, 13C/12C and 15N/14N ratios provided by NanoSIMS was evaluated.

METHODS

The spatial organization of soil particles found at the macro‐ and micro‐scales were compared. The C/N, 13C/12C and 15N/14N ratios measured at the macroscopic scale from different density fractions using an elemental analyzer coupled to an isotope ratio mass spectrometer (EA/IRMS) were compared with the corresponding micro‐scale NanoSIMS measurements. When the macro‐ and micro‐scales patterns were similar, macroscopic scale measurements obtained by EA/IRMS and the corresponding NanoSIMS C/N and 15N/14N ratios averaged per fraction were used to obtain correction equations. The correction method using the internal calibration procedure was compared with the traditional one using a single organic standard.

RESULTS

It was demonstrated that the correction method using an internal calibration procedure was applicable for NanoSIMS images acquired on more than 500 µm2 per fraction and provided more accurate C/N and 15N/14N ratios than the traditional correction method.

CONCLUSIONS

As long as the NanoSIMS sampling was representative of the macroscopic properties, the correction method using an internal calibration procedure allowed better quantification of the isotope tracers and characterization of the C/N ratios. This method not only produced qualitative images, but also accurate quantitative parameters from which ecological interpretations can be derived. Copyright © 2012 John Wiley & Sons, Ltd.