bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Paramagnetic Effects through a Tagged Reporter Protein
Authors: Camacho‐Zarco Aldo R. , Munari Francesca , Wegstroth Melanie , Liu Wei‐Min , Ubbink Marcellus , Becker Stefan , Zweckstetter Markus
Published: October 2014

Paramagnetic effects provide unique information about the structure and dynamics of biomolecules. We developed a method in which the lanthanoid tag is not directly attached to the protein of interest, but instead to a “reporter” protein, which binds and then transmits paramagnetic information to the target. The designed method allows access to a large number of paramagnetic restraints and residual dipolar couplings produced from independent molecular alignments in high‐molecular‐weight proteins with unknown 3D structure
pH‐Responsive Drug‐Delivery Systems
Authors: Zhu Ying‐Jie , Chen Feng
Published: October 2014

In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH‐Responsive drug‐delivery systems have attracted more and more interest as “smart” drug‐delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH‐responsive drug‐delivery systems; instead, it presents some recent progress obtained for pH‐responsive drug‐delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed.
Dithienopyrrole as a Rigid Alternative to the Bithiophene π Relay in Chromophores with Second‐Order Nonlinear Optical Properties
Authors: Marco A. Belén , Martínez de Baroja Natalia , Franco Santiago , Garín Javier , Orduna Jesús , Villacampa Belén , Revuelto Alejandro , Andreu Raquel
Published: October 2014

4H‐Pyranylidene‐containing push‐pull chromophores built around a bithiophene (BT) π relay or a rigidified thiophene‐based unit, namely cyclopenta[1,2‐b:3,4‐b′]dithiophene (CPDT) or dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP), have been synthesized and characterized. The effect of these different relays on the polarization and the second‐order nonlinear optical (NLO) properties has been studied. For the sake of comparison, the corresponding reported dithieno[3,2‐b:2′,3′‐d]thiophene (DTT) derivatives have also been included in the discussion. Replacement of the BT core by a rigidified unit (CPDT, DTP) leads to more polarized systems. Calculated NBO charges and electrochemical measurements show that dithienopyrrole has a remarkable donor character that allows an important charge transfer between the donor and the acceptor. The influence of the rigidification of the BT relay on the NLO responses depends on the acceptor strength. For the weakest acceptor used (thiobarbituric acid), passing from the BT relay to the rigidified units always involves an increase in the μβ0 figure of merit. Nevertheless, for the strongest acceptor (2‐dicyanomethylene‐3‐cyano‐4,5,5‐trimethyl‐2,5‐dihydrofuran (TCF)), a slight increase in μβ0 with respect to the BT chromophore is only observed for the DTP derivative. Thus, rigidification of the BT core is not enough to improve the second‐order nonlinearity and the incorporation of a DTP moiety has proven to be the most efficient approach for this purpose.
Phototandem Catalysis: Efficient Synthesis of 3‐Ester‐3‐hydroxy‐2‐oxindoles by a Visible Light‐Induced Cyclization of Diazoamides through an Aerobic Oxidation Sequence
Authors: Xia Xu‐Dong , Ren Yan‐Liang , Chen Jia‐Rong , Yu Xing‐Long , Lu Liang‐Qiu , Zou You‐Quan , Wan Jian , Xiao Wen‐Jing
Published: October 2014

An unprecedented phototandem catalysis based on a single iridium photocatalyst has been successfully developed. This powerful strategy consists of two mechanistically distinct catalytic cycles, namely, photocatalytic energy transfer (ET) and single electron transfer (SET). The novel protocol allows a rapid and efficient construction of biologically and synthetically important 3‐ester‐3‐hydroxy‐2‐oxindole derivatives from readily available diazoamides through a cyclization/aerobic oxidation sequence under very mild conditions.
An evaluation of CORDEX regional climate models in simulating precipitation over Southern Africa
Authors: Shongwe Mxolisi E. , Lennard Chris , Liebmann Brant , Kalognomou Evangelia‐Anna , Ntsangwane Lucky , Pinto Izidine
Published: October 2014

This article evaluates the ability of the Coordinated Regional Downscaling Experiment (CORDEX) regional climate models (RCMs) in simulating monthly rainfall variation during the austral summer half year (October to March) over southern Africa, the timing of the rainy season and the relative frequencies of rainfall events of varying intensities. The phasing and amplitude of monthly rainfall evolution and the spatial progression of the wet season onset are well simulated by the models. Notwithstanding some systematic biases in a few models, the simulated onset and end of the rainy season and their interannual variability are highly correlated with those computed from the reference data. The strongest agreements between the reference and modelled precipitation patterns are found north of about 20°S in the vicinity of the Inter Tropical Convergence Zone. A majority of the RCMs adequately capture the reference precipitation probability density functions, with a few showing a bias towards excessive light rainfall events.
Concentrated portfolio selection models based on historical data
Authors: Chen Zhiping , Li Zongxin , Wang Liyuan
Published: October 2014

A new risk measure fully based on historical data is proposed, from which we can naturally derive concentrated optimal portfolios rather than imposing cardinality constraints. The new risk measure can be expressed as a quadratics of the introduced greedy matrix, which takes investors' joint behavior into account. We construct distribution‐free portfolio selection models in simple case and realistic case, respectively. The latest techniques for describing transaction cost constraints and solving nonconvex quadratic programs are utilized to obtain the optimal portfolio efficiently. In order to show the practicality, efficiency, and robustness of our new risk measure and corresponding portfolio selection models, a series of empirical studies are carried out with trading data from advanced stock markets and emerging stock markets. Different performance indicators are adopted to comprehensively compare results obtained under our new models with those obtained under the mean‐variance, mean‐semivariance, and mean‐conditional value‐at‐risk models. Out‐of‐sample results sufficiently show that our models outperform the others and provide a simple and practical approach for choosing concentrated, efficient, and robust portfolios. Copyright © 2014 John Wiley & Sons, Ltd.
Isolated limb perfusion using tumour necrosis factor α and melphalan in patients with advanced aggressive fibromatosis
Authors: van Broekhoven D L M , Deroose J P , Bonvalot S , Gronchi A , Grünhagen D J , Eggermont A M M , Verhoef C
Published: October 2014

Background

Aggressive fibromatoses (desmoid tumours) may be locally aggressive, but do not metastasize. Although a conservative approach is advocated for most patients, pain and functional impairment are indications for active treatment. Tumour necrosis factor (TNF) α and melphalan-based isolated limb perfusion (TM-ILP) is a limb-saving treatment modality for soft tissue tumours. This study reports the results of TM-ILP treatment in patients with aggressive fibromatosis.

Methods

Institutional databases of three European centres were searched. All patients who received TM-ILP treatment for aggressive fibromatosis between 1990 and 2012 were included. Before therapy, the patients were discussed at multidisciplinary tumour board meetings.

Results

Twenty-five patients received 28 TM-ILP treatments. The median age of patients was 28 (i.q.r. 19–34) years and median hospital stay was 8 (7–12) days. Median follow-up was 84 (34–114) months. A complete response was achieved after two TM-ILP treatments, and a partial response after 17 treatments in 16 patients. Stable disease was reported after eight treatments in seven patients, including a patient with stable disease after the first treatment and progression after the second TM-ILP. Toxicity was modest after most treatments; Wieberdink grade IV (extensive epidermolysis, and threatening or manifest compartment syndrome) was seen after two TM-ILP treatments. Systemic leakage was reported after one treatment, but did not lead to systemic toxicity. Functional outcome was good; 16 patients had no physical limitations, and six patients had some limitations but did not need medical aids. Amputation was prevented in all but three patients.

Conclusion

TNF-α-based ILP is effective in patients with aggressive fibromatosis.
A retrospective analysis of cross‐reacting cetuximab IgE antibody and its association with severe infusion reactions
Authors: Maier Sabine , Chung Christine H. , Morse Michael , Platts‐Mills Thomas , Townes Leigh , Mukhopadhyay Pralay , Bhagavatheeswaran Prabhu , Racenberg Jan , Trifan Ovidiu C.
Published: October 2014

Severe infusion reactions (SIRs) at rates of 5% or less are known side effects of biological agents, including mAbs such as cetuximab. There are currently no prospectively validated risk factors to aid physicians in identifying patients who may be at risk of experiencing an SIR following administration of any of these drugs. A retrospective analysis of 545 banked serum or plasma samples from cancer patients participating in clinical trials of cetuximab was designed to evaluate whether the presence of pretreatment IgE antibodies against cetuximab, as determined by a commercially available assay system, is associated with SIRs during the initial cetuximab infusion. Patients with a positive test indicating the presence of pretreatment antibodies had a higher risk of experiencing an SIR; however, at the prespecified cutoff utilized in this analysis, the test has a relatively low‐positive predictive value (0.577 [0.369–0.766]) and a negative predictive value of 0.961 (0.912–0.987) in an unselected patient population. Data collected in this large retrospective validation study support prior observations of an association between the presence of pretreatment IgE antibodies cross‐reactive with cetuximab and SIRs. Further analysis of the test's ability to predict patients at risk of an SIR would be required before this assay could be used reliably in this patient population.
‘An Association for All’—Notions of the Meaning of Autistic Self‐Advocacy Politics within a Parent‐Dominated Autistic Movement
Authors: Bertilsdotter Rosqvist Hanna , Brownlow Charlotte , O'Dell Lindsay
Published: October 2014

In this paper, we seek to explore the tensions between advocacy and self advocacy autistic movements in a Swedish context with a special focus on the meanings that enable the production of particular understandings of autism and the autistic subject. Drawing on articles written for the Swedish advocacy magazine Empowerment written for and by people with autism, the discourse analysis explores two competing discourses: a reformist and a radical. The reformist discourse underlines a goal of (political) representation expressed in Empowerment. It may be understood as an important part of producing a legitimate autistic political subject–positioned as a full member, with a full membership–within a parent‐dominated autistic advocacy movement. The reformist discourse can be viewed as a result of a negotiation, where full membership is conditioned on the parents' terms and granted on specific terms. These include working together (neuro‐inclusively), advocacy based on interest rather than identity/position as a specific target/member group, agreement upon a definition of autism as a disability (a deficit) a person has rather than an identity. In relation to this, an alternative legitimate autistic subject is produced through invoking the counter‐hegemonic radical discourse. Such a narrative produces the ‘Asperger’ or ‘Aspie’. Here, the ‘full membership’ refers to a sense of identification with sense of belonging to and being at home with other people with autism. It contains a certain amount of autistic solidarity within the group of adults with autism. Copyright © 2014 John Wiley & Sons, Ltd.
The Community Psychologist as Critical Friend: Promoting Critical Community Praxis
Authors: Evans Scotney D.
Published: October 2014

Community‐engaged researchers have a responsibility to community partners to get beyond the traditional researcher stance to take on the active role of critical friend. On the basis of my own community research experiences in the USA, in this article, I argue that there is added value in taking on the practice of critical friendship to encourage a higher degree of critical reflection and critical practice in our partners and in our work together. In the context of long‐term, trusting relationships with community partners, researchers can play the role of critical friend working together to shape critical community praxis on the basis of critical theorizing, critical reflection, and a shared commitment to working for social justice. Those trying to make a difference in communities are often isolated and can benefit from opportunities for dialogue with other community practitioners within a critical frame of reference. Although not without risks and challenges, stepping into this role allows us to put into sharper relief the gap between community practice that challenges injustice and practice that maintains it. Copyright © 2014 John Wiley & Sons, Ltd.
Cloning of a functional 25‐hydroxyvitamin D‐1α‐hydroxylase in zebrafish (Danio rerio)
Authors: Chun Rene F. , Blatter Elizabeth , Elliott Stephanie , Fitz‐Gibbon Sorel , Rieger Sandra , Sagasti Alvaro , Adams John S. , Hewison Martin
Published: October 2014

Activation of precursor 25‐hydroxyvitamin D3 (25D) to hormonal 1,25‐dihydroxyvitamin D3 (1,25D) is a pivotal step in vitamin D physiology, catalysed by the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (1α‐hydroxylase). To establish new models for assessing the physiological importance of the 1α‐hydroxylase‐25D‐axis, we used Danio rerio (zebrafish) to characterize expression and biological activity of the gene for 1α‐hydroxylase (cyp27b1). Treatment of day 5 zebrafish larvae with inactive 25D (5–150 nM) or active 1,25D (0.1–10 nM) induced dose responsive expression (15–95‐fold) of the vitamin D‐target gene cyp24a1 relative to larvae treated with vehicle, suggesting the presence of Cyp27b1 activity. A full‐length zebrafish cyp27b1 cDNA was then generated using RACE and RT‐PCR methods. Sequencing of the resulting clone revealed an open reading frame encoding a protein of 505 amino acids with 54% identity to human CYP27B1. Transfection of a cyp27b1 expression vector into HKC‐8, a human kidney proximal tubular epithelial cell line, enhanced intracrine metabolism of 25D to 1,25D resulting in greater than twofold induction of CYP24A1 mRNA expression and a 25‐fold increase in 1,25D production compared to empty vector. These data indicate that we have cloned a functional zebrafish CYP27B1, representing a phylogenetically distant branch from mammals of this key enzyme in vitamin D metabolism. Further analysis of cyp27b1 expression and activity in zebrafish may provide new perspectives on the biological importance of 25D metabolism. Copyright © 2014 John Wiley & Sons, Ltd.
Towards Multifunctional Materials Incorporating Elastomers and Reversible Redox‐Active Fragments
Authors: Tarrés Màrius , Viñas Clara , Cioran Ana M. , Hänninen Mikko M. , Sillanpää Reijo , Teixidor Francesc
Published: October 2014

This paper presents a novel and unique feature of metallacarboranes, consisting of the linkage of this redox electro‐active site to a stretchable polymer. This is based on polyTHF, a known and applied material. This hybrid material has the two ends functionalized: one with the aforementioned redox molecule and the other with a terminal OH group, both linked by a molecular spring. Moreover, the redox electro‐active molecules can be synthesized with either cobalt (cobaltabisdicarbollide) or with iron (ferrabisdicarbollide), species whose respective E1/2 value differs by almost 1 V. The polymerization mechanism, based on an intermediate molecular crystal structure, is explained through an unexpected cyclization process of the dioxanate derivative of the metallacarboranes with an additional THF molecule. This is achieved in the absence of any metal or external electrophile. Surface functionalization of a Pt electrode by the electropolymerization of pyrrole doped with the pristine metallacarboranes and with the polyTHF hybrid materials is reported in this paper.
Restriction of Intramolecular Motions: The General Mechanism behind Aggregation‐Induced Emission
Authors: Leung Nelson L. C. , Xie Ni , Yuan Wangzhang , Liu Yang , Wu Qunyan , Peng Qian , Miao Qian , Lam Jacky W. Y. , Tang Ben Zhong
Published: October 2014

Aggregation‐induced emission (AIE) has been harnessed in many systems through the principle of restriction of intramolecular rotations (RIR) based on mechanistic understanding from archetypal AIE molecules such as tetraphenylethene (TPE). However, as the family of AIE‐active molecules grows, the RIR model cannot fully explain some AIE phenomena. Here, we report a broadening of the AIE mechanism through analysis of 10,10′,11,11′‐tetrahydro‐5,5′‐bidibenzo[a,d][7]annulenylidene (THBDBA), and 5,5′‐bidibenzo[a,d][7]annulenylidene (BDBA). Analyses of the computational QM/MM model reveal that the novel mechanism behind the AIE of THBDBA and BDBA is the restriction of intramolecular vibration (RIV). A more generalized mechanistic understanding of AIE results by combining RIR and RIV into the principle of restriction of intramolecular motions (RIM).
One‐Step Double Covalent Functionalization of Reduced Graphene Oxide with Xanthates and Peroxides
Authors: Pennetreau Florence , Riant Olivier , Hermans Sophie
Published: October 2014

Radical functionalization of reduced graphene oxide has been achieved by reaction with a xanthate in the presence of peroxide as a radical initiator. X‐ray photoelectron spectroscopy, bulk elemental analyses, and thermogravimetric analyses showed that the xanthate grafting is covalent and efficient. The synthesis and use of seven xanthates and three peroxides showed that the highest grafting yield is obtained when xanthate and peroxide are introduced in stoichiometric amounts. It also revealed that the peroxide used as radical initiator is grafted at the graphenic surface during the functionalization. The method presented in this contribution therefore allows bifunctionalized reduced graphene oxide samples to be easily obtained in one single step. This method leads to undamaged graphene sheets with higher dispersibility than the pristine sample.
Chemoinformatik
Authors: Engel Thomas
Published: October 2014

Dieser Artikel ermöglicht einen ersten Einblick in das faszinierende Gebiet und die Vielzahl der eingesetzten Methoden der Chemoinformatik. Leider mussten aus Platzgründen weitere interessante Bereiche ausgespart bleiben, z.B. das Molecular Modelling [13] oder die Chemometrie [14]. Dennoch ist ersichtlich, dass Methoden der Chemoinformatik in viele Bereiche der Chemie Einzug gehalten haben, von der Analytischen Chemie über Materialforschung bis hin zur Wirkstoffforschung, und dort wesentliche Beiträge leisten. Im Mittelpunkt steht hierbei immer die chemische Information der Moleküle, welche erzeugt, organisiert, verwaltet, suchbar gemacht, analysiert und visualisiert werden muss.
Eine haarige Angelegenheit
Authors: Feil Sylvia
Published: October 2014

Obwohl haarige Zellfortsätze, sogenannte Flimmerhärchen oder Zilien, schon lange bekannt sind, ist noch recht unerforscht, wie ihr Zusammenbau bei der Differenzierung von Zellen gesteuert wird. Für die Flimmerhärchen auf dem Epithel von Lunge und Luftröhre spielen offenbar sechs Mikro‐RNAs in diesem Prozess eine Schlüsselrolle [1].
Einfacher Weg zu Chromanol‐Antioxidantien
Authors: Jaenicke Lothar
Published: October 2014

Tocopherole sind natürliche fettlösliche, äußerst wirksame Bio‐Antioxidantien, hilfreich gegen die in unserem aeroben Lebensraum überall vorhandenen reaktiven, äußerst toxischen, freien Sauerstoffradikale (ROS). Sie werden daher vielfach in der Lebensmittelindustrie eingesetzt. Allerdings ist ihre Synthese teuer und aufwendig. Basis für einen einfacheren Zugang könnte eine neue Synthese zu 6‐Chromanolen sein [1].
Eliminating cost‐sharing requirements for colon cancer screening in Medicare
Authors: Howard David H. , Guy Gery P. , Ekwueme Donatus U.
Published: October 2014

Medicare beneficiaries do not have to pay for screening colonoscopies but must pay coinsurance if a polyp is removed via polypectomy. Likewise, beneficiaries do not have to pay for fecal occult blood tests but are liable for cost‐sharing for diagnostic colonoscopies after a positive test. Legislative and regulatory requirements related to colorectal cancer screening are described, and on the basis of Medicare claims, it is estimated that Medicare spending would increase by $48 million annually if Medicare were to waive cost‐sharing requirements for these services. The economic impact on Medicare if beneficiaries were not responsible for any cost‐sharing requirements related to colorectal cancer screening services is described. Cancer 2014;120:3850–3852. © 2014 American Cancer Society.
Optimum solution of the CIECAM02 yellow–blue and purple problems
Authors: Jiang Jun , Wang Zhifeng , Luo M. Ronnier , Melgosa Manuel , Brill Michael H. , Li Changjun
Published: October 2014

Brill [Color Res Appl 2006;31:142‐145] and Brill and Süsstrunk [Color Res Appl 2008;33:424‐426] found that CIECAM02 has the yellow–blue and purple problems and gave partial solutions to them. In this article we model the optimum solution to the yellow–blue and purple problems simultaneously as a constrained non‐linear optimization problem. An optimum solution resulting in a new CAT02 matrix is numerically obtained. This new matrix satisfies the nesting rule and performs better than the Hunt‐Pointer‐Estévez (HPE) matrix in predicting both corresponding colours and colour appearance data sets. Specifically, it was found that the new and HPE matrices performed significantly different on nine (out of 21) corresponding colour data sets and on all corresponding colours data sets as a whole. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 491–503, 2015
Twinning in GaAs nanowires on patterned GaAs(111)B
Authors: Walther Thomas , Krysa Andrey B.
Published: October 2014

We have studied twinning in GaAs nanowires grown via holes in a silica mask deposited on GaAs(111)B substrates by metal‐organic chemical vapour epitaxy without catalysts. Twins perpendicular to the growth direction form in the nanowires, their {111}‐type side facets leading to corrugation of their {110} side walls. The top facets are almost atomically smooth. Aberration corrected annular dark‐field scanning transmission electron microscopy reveals all twins are rotational, commencing with layers of Ga and finishing with As atoms. Energy‐loss spectroscopic profiling has shown no significant changes in the band‐gap or bulk plasmon energy at those twin boundaries, and the observed reduction of the interface plasmon energy by ∼0.13 eV is close to the detection limit of the technique, reflecting the very low energetic electronic changes related to twin formation.
Low‐complexity joint detection of carrier frequency offset and sector cell index for LTE cellular system
Authors: Kim Byung‐Kyu , Song Hyoung‐Kyu , You Young‐Hwan
Published: October 2014

In this paper, we propose a low‐complexity joint detection of sector cell index and integer carrier frequency offset for a long‐term evolution downlink system. In order to implement a low‐cost detection scheme, a primary synchronization signal used for joint parameter estimation is grouped into a number of subsets so that the pilots in each subset are strongly correlated. The estimation performance and the computational load of the proposed scheme are compared with those of the commonly used conventional detection scheme using a differential correlation to remove common channel effects. It is found that the proposed scheme can jointly detect the cell index and integer carrier frequency offset with higher accuracy and much lower complexity, compared with the conventional scheme. Copyright © 2014 John Wiley & Sons, Ltd.
Life history of a cyprinid species in non‐regulated and regulated rivers from permanent and temporary Mediterranean basins
Authors: Alexandre C. M. , Ferreira M. T. , Almeida P. R.
Published: October 2014

Streamflow variability, natural and human induced, has been suggested as a driver of life history differences among freshwater fish populations. During 1 year, we collected bimonthly and fortnightly samples from four populations of Iberian barbel, inhabiting permanent and temporary Mediterranean rivers with non‐regulated and regulated flow regimes. We analysed data for fish age, growth and reproduction to (i) compare barbels' life cycles between permanent and temporary non‐regulated rivers; (ii) assess the effect of two types of flow alteration in these traits; and (iii) identify flow variables significantly related with growth and reproductive cycles. Regional differences were related with the age of first maturation, growth rate and timing and duration of the reproductive season. Flow regulation promoted a decrease of fish growth rates, condition and gonad activity and an increase of maximum length and longevity. Seasonal variation of growth and gonad maturation were related with temperature and streamflow components. This study offers a multi‐regional perspective of the relationship between fish biological cycles and streamflow variability, providing water resource managers with needed perspective about the effect of anthropogenic alteration of streamflow magnitudes. Copyright © 2014 John Wiley & Sons, Ltd.
CE‐MS for metabolomics: Developments and applications in the period 2012–2014
Authors: Ramautar Rawi , Somsen Govert W. , de Jong Gerhardus J.
Published: October 2014

In the field of metabolomics, CE‐MS is now regarded as a useful complementary analytical technique for the profiling of (highly) polar ionogenic metabolites in biological samples. Over the past few years, significant advancements have been made in CE‐MS approaches for metabolic profiling studies. This paper, which is a follow‐up of three previous review papers covering the years 2000–2012 [Electrophoresis 2009, 30, 276–291; Electrophoresis 2011, 32, 52–65; Electrophoresis 2013, 34, 86–98], provides an update of these developments covering the scientific literature from July 2012 to June 2014. Attention will be paid to novel interfacing techniques for coupling CE to MS and their implications for metabolomics studies. The potential of CEC‐MS and MEKC‐MS are also considered, and CE‐MS systems for high‐throughput metabolic profiling are discussed. The applicability of CE‐MS for metabolomics studies is demonstrated by representative examples in the fields of biomedical, clinical, microbial, plant, environmental, and food metabolomics. An overview of recent CE‐MS‐based metabolomics studies is given in a table, which provides information on sample type and pretreatment, capillary coatings, and MS detection mode. Finally, general conclusions and perspectives are given.
Diamondoid‐Structured Cu–Dicarboxylate‐based Metal–Organic Frameworks as High‐Capacity Anodes for Lithium‐Ion Storage
Authors: Senthil Kumar R. , Nithya C. , Gopukumar S. , Anbu Kulandainathan M.
Published: October 2014

A versatile electrochemical synthetic route is proposed for the preparation of [Cu2(C8H4O4)4]n metal–organic frameworks. The synthesized composites are characterized by using XRD, SEM, FTIR, and Brunauer–Emmett–Teller (BET) surface analysis. The average particle size was measured to be 8.27 nm and the pore size determined to be 14.06 nm. Here, for the first time, we demonstrate the Cu‐based metal–organic frameworks [Cu2(C8H4O4)4]n as a new class of porous crystalline materials that have the ability to reversibly store Li+ ions. Galvanostatic charge/discharge studies suggest that the terephthalate network reversibly reacts with Li and shows high capacity retention (≈84 % over 50 cycles). The best reversible capacity of 227 mAh g−1 (approximately 95 % of the theoretical capacity) has been achieved in the first cycle at a current density of 24 mA g−1. An easily scalable electrochemical synthesis of the [Cu2(C8H4O4)4]n metal–organic frameworks is an attractive candidate for use with lithium‐ion batteries.
Round‐Robin Studies on Roll‐Processed ITO‐free Organic Tandem Solar Cells Combined with Inter‐Laboratory Stability Studies
Authors: Livi Francesco , Søndergaard Roar R. , Andersen Thomas R. , Roth Bérenger , Gevorgyan Suren , Dam Henrik F. , Carlé Jon E. , Helgesen Martin , Spyropoulos George D. , Adams Jens , Ameri Tayebeh , Brabec Christoph J. , Legros Mathilde , Lemaitre Noëlla , Berny Stephane , Lozman Owen R. , Schumann Stefan , Scheel Arnulf , Apilo Pälvi , Vilkman Marja , Bundgaard Eva , Krebs Frederik C.
Published: October 2014

Roll‐processed, indium tin oxide (ITO)‐free, flexible, organic tandem solar cells and modules have been realized and used in round‐robin studies as well as in parallel inter‐laboratory stability studies. The tandem cells/modules show no significant difference in comparison to their single‐junction counterparts and the use of round‐robin studies as a consensus tool for evaluation of organic solar cell parameters is judged just as viable for the tandem solar cells as for single‐junction devices. The inter‐laboratory stability studies were conducted according to testing protocols ISOS‐D‐2, ISOS‐D‐3, and ISOS‐L‐2, and in spite of a much more complicated architecture the organic tandem solar cells show no significant difference in stability in comparison to their single‐junction counterparts.
On the impact of covariate measurement error on spatial regression modelling
Authors: Huque Md Hamidul , Bondell Howard D. , Ryan Louise
Published: October 2014

Spatial regression models have grown in popularity in response to rapid advances in geographic information system technology that allows epidemiologists to incorporate geographically indexed data into their studies. However, it turns out that there are some subtle pitfalls in the use of these models. We show that the presence of covariate measurement error can lead to significant sensitivity of parameter estimation to the choice of spatial correlation structure. We quantify the effect of measurement error on parameter estimates and then suggest two different ways to produce consistent estimates. We evaluate the methods through a simulation study. These methods are then applied to data on ischaemic heart disease. Copyright © 2014 John Wiley & Sons, Ltd.
Training the Next Generation
Authors: Kopp Susan
Published: October 2014

As an educator in an urban veterinary technology program, I often encounter students beginning their professional studies who are passionate about their commitment to a career working with animals. Typically, they have also firmly decided that they will never accept a job in the animal research field. They object to animal research in general because of what they assume is the abject mistreatment of animals housed in laboratories.

Chatting again with these students two years later as they prepare for graduation, however, I am increasingly finding that many reconsider those firm convictions. In fact, even in a strong job market for veterinary technicians, some of these graduates are actually choosing to enter the laboratory animal care field.

What is causing such an about‐face?
Raising the Bar: The Implications of the IOM Report on the Use of Chimpanzees in Research
Authors: Kahn Jeffrey
Published: October 2014

I had the privilege of chairing the Institute of Medicine Committee on the Necessity of Chimpanzees in Biomedical and Behavioral Research in 2011, an effort that has lessons not only about the questions presented to it, but also about the policy and practice of the use of chimpanzees in research and about animal research policy in general. In this essay I will assess the impact and implications of the committee's work and at the same time clarify what I see as its limits. All in all, I believe it is fair to say that the committee's recommendations and the process of its work represent a success for bioethics‐related consensus committees. The combination of topic, timing, and public stakeholder sentiment may have aligned in unique ways that contributed to that success. But even if it turns out to be a special case of sorts, there are lessons to be learned for the future.
U.S. Law and Animal Experimentation: A Critical Primer
Authors: Latham Stephen R.
Published: October 2014

Every country's law permits medical experimentation on animals. While some countries protect particular kinds of animals from being subject to experimentation—notably great apes and endangered species—very few place concrete limitations on what researchers may cause animals to suffer, given sufficient scientific justification. What laws do, instead, is establish standards for the humane treatment and housing of animals in labs, and they encourage researchers to limit or seek alternatives to the use of animals, when doing that is consistent with the scientific goals of their research.

The system that has evolved in the United States combines elements of sometimes competing regulatory philosophies. The result is a complex, multilayered system that addresses the most important concerns, but, partly because of historical accident, also leaves some gaps. Even proponents of medical research on animals can see obvious ways in which the regulatory structure could be changed to benefit animals. Perhaps more important, though, is the fact that the existing regulatory structure, imperfect though it may be, is elastic enough to accommodate substantial changes that could reduce unnecessary animal suffering.
The Outsider
Authors: TOMASIC VERONICA
Published: October 2014

On occasion, I am appointed by our local probate court to help make health care decisions for patients who are no longer capable of making these decisions for themselves. I'll visit my client in the hospital and review his or her chart, and I'll have numerous opportunities to talk about the illness and treatment options with attending physicians, residents, and nurses. My phone calls to them will be returned promptly. If doctors arrive at the conclusion that nothing further can be done for the patient, we'll discuss how best to proceed. This end‐of‐life talk never comes as a surprise to me because I will have been included in the team's decision‐making process, in the manner of professionals interacting with another professional.

Last fall, I became a family surrogate decision‐maker after my mother was hospitalized over the course of a few months, for a number of reasons, in three hospitals in New York. I assumed I would manage her care as I did my clients’, with a sense of control and involvement in the process, but I quickly learned that I had in fact entered a kind of alternate universe as far as decision‐making was concerned.
Ethical Oversight of Research on Patient Care
Authors: Solomon Mildred Z. , Bonham Ann C.
Published: October 2014

The Institute of Medicine has called on health care leaders to transform their health systems into “learning health care systems,” capable of studying and continuously improving their practices. Learning health care systems commit to carrying out numerous kinds of investigations, ranging from clinical effectiveness studies to quality improvement research and implementation science. There has been progress in realizing the IOM's vision, but also many challenges. One of these challenges has been lingering uncertainty about whether the data collection and monitoring central to learning health care systems is actually research and if so, what kind of ethical oversight it should have. This is not a new question. Yet so far, there has been no foundational analysis of the fit between the existing human subjects protection framework in use in the United States and the new kinds of data collection activities that are being, and increasingly will be, undertaken by learning health care systems. Two companion feature articles in this volume, by a team at Johns Hopkins, fill this void.
The Unbelievable Rightness of Being in Clinical Trials
Authors: Menikoff Jerry
Published: October 2014

Much of what Ruth Faden and colleagues say squarely meshes with the ideas of the U.S. Department of Health and Human Services about reforming the system for protecting research subjects. Having said that, I want to turn to a very different part of the research universe, the elephant in the room, as it were: the world of interventional randomized clinical trials. Under the current regulatory system, these research subjects receive substantial protections. Most importantly, they are generally enrolled only after they give their informed consent. The rationale for this approach is that research subjects are denied the core ethical protection provided to patients: there is no requirement that everything done to them be in their best interests. Faden and colleagues appear to be proposing to eliminate this informed consent requirement for a significant range of such trials.
Making the Transition to a Learning Health Care System
Authors: Grady Christine , Wendler David
Published: October 2014

The authors of the two main articles in this supplement recognize the enormous potential of learning health care systems. Their first article argues that the development of these systems calls into question existing guidelines and practices that treat clinical care and clinical research as distinct activities. Their second article proposes to replace this traditional approach with a new framework, one intended to promote two important goals: support the transformation to a learning health care system and help to ensure the ethical appropriateness of the activities carried out within such a system. To promote these goals, the authors propose a framework consisting of seven obligations. The authors are aware that their framework does not provide much guidance for promoting their second goal. At first glance, the seven obligations also might appear to offer little in the way of promoting the first goal. In what way, then, is the proposed framework novel and transformative, as the authors claim? The answer appears to lie largely in how the authors interpret the sixth obligation in the framework—the obligation to conduct learning activities.
Reform within the Common Rule?
Authors: Puglisi Tom
Published: October 2014

In their papers in this supplement, Ruth Faden and colleagues conclude that research ethics and regulation must change to accommodate a changed and changing health care environment. The reality, however, is that the widely understood and accepted ethical framework embedded in the regulatory requirements known as the Common Rule, and recent proposals to modify the Common Rule have become stalled, at least for the foreseeable future, if not permanently. Meaningful systemic modernization of the Common Rule is not likely to occur any time soon. All the same, modernization of the Common Rule is desperately needed. In the short term, the agencies responsible for implementing it must be willing to develop practical guidance for implementing the current regulatory requirements in a way that promotes clarity and understanding and allocates human and fiscal resources based on the level of risk to subjects. To this end, the Veterans Health Administration recently implemented policy to address the research‐practice distinction—a distinction that is especially relevant to VHA's current challenges and that the authors of the “ethical framework” articles have identified as particularly outmoded.
Advances in the Research Enterprise
Authors: Kupersmith Joel
Published: October 2014

The clinical research enterprise is changing in fundamental ways. The bright line that separates research and clinical care is beginning to fade, as both “research” and “nonresearch” converge into and are embodied by the concept of the learning health care system. Here, data about care and operations are translated into practice improvement. VA has been a leader in this area, and based on its use of electronic health records and other inputs, has formed large databases and a data‐driven health care system. These changes raise questions about the traditional approach to “research subject” protection.
Living morally, and happily
Authors: Scheinerman Naomi
Published: October 2014

Society's distribution of goods is not always just: there is a significant lack of jobs and resources accessible to even the hardest of workers, and even the most motivated can have trouble discovering that fulfilling calling. Furthermore, the most needed jobs may, for many, not be the most fulfilling ones, while the most fulfilling jobs may not always better society. Amidst such observations, I find myself reflecting on my own life choices. Working at The Hastings Center is an exceedingly rare opportunity for which I am extremely grateful: it allows me to combine my life passion and my hopes for a moral society with allocating my time in ways that are both fulfilling momentarily and hopefully contribute to a future career in the field.
Information Ethics
Authors: Kaebnick Gregory E.
Published: October 2014

The use of information raises a perplexing new set of questions in bioethics. One familiar subset of these has to do with the goal of improving medical practice by collecting information about it, in effect integrating practice and research. This topic was discussed in the January‐February 2013 issue of the Report and in this issue is taken up again in Policy and Politics, where Michelle Meyer connects the issue to the evidence‐based medicine movement.

A somewhat less familiar set has to do with potentially dangerous information. In the lead article in this issue, David Resnik discusses the publication last year of two articles that described how researchers had developed new and more dangerous forms of H5N1, also known as bird flu, which has produced an extraordinary death rate when it has infected people but has not so far evolved into a form that can be easily transmitted from one person to another.

Yet another set has to do with sharing clinical medical information using newly developed tools such as electronic health records. In an essay in this issue, Kyle Galbraith argues that these technologies also need to be usable for patients, but that “those who have the most to gain from increased access to their health information are often unlikely to be able to decipher that information and respond in a meaningful way.”
More Rhetoric Than Argument?
Authors: Feder Ellen K. , Dreger Alice , Tamar‐Mattis Anne
Published: October 2014

One of two commentaries on “Normalizing Atypical Genitalia: How a Heated Debate Went Astray,” by Josephine Johnston, from the November‐December 2012 issue.
“Ever Vigilant” in “Ethically Impossible”
Authors: Galarneau Charlene
Published: October 2014

The report from the Presidential Commission for the Study of Bioethical Issues is clear that the public health services research conducted in Guatemala mid‐century was wrong, but its focus on individual responsibilities is inadequate for the structural and institutional factors at the root of that research.

Ethically Impossible”: STD Research in Guatemala from 1946 to 1948, released in September 2011 by the Presidential Commission for the Study of Bioethical Issues, 1 responds to President Obama's request for a “thorough fact‐finding investigation” into research carried out by the U.S. Public Health Service in Guatemala from 1946 to 1948. “Ethically Impossible” offers a detailed narrative of what happened in Guatemala and a self‐described “unvarnished ethical analysis.” I argue, however, that being “ever vigilant” to prevent exploitation, as well as learning as a society from this past and honoring the memory of Guatemalan victims, requires a more complex ethical analysis than the commission offers in this report. Specifically, we need to identify the structural injustices that innervated the social relations and the institutions fundamental to the moral landscape of this 1940s research, and we need to expand our understandings of moral responsibility accordingly. The report posits three “longstanding and widely accepted moral principles” as the framework for evaluating this research: (1) to treat persons fairly and with respect, (2) not to harm (or risk harming) persons unless the risk is reasonable and the benefit proportional, and (3) not to treat persons as means to others’ ends. As critically important as the three principles are to research ethics writ large, they alone are unfitting tools for addressing the kind of structural and institutional moral factors that are so important in these PHS studies.
Exchanges on Obesity and Smoking
Authors: Kaebnick Gregory E.
Published: October 2014

The January‐February issue of the Report introduced a number of new features designed to provide opportunities for further give‐and‐take in our pages. In this issue, we put to use our revamped letters to the editor, Exchange, with a set of commentaries on another of the January‐February articles, Daniel Callahan's “Obesity: Chasing an Elusive Epidemic.” Commentaries in Other Voices and special reports are planned and solicited, in consultation with scholars in the field and with the guest editors of the special reports, but our hope is that Exchange will provide an opportunity for unsolicited voices in the Report. Of course, Callahan's controversial article is all too good for drumming up unsolicited commentary: Callahan argued that the rise in obesity requires an aggressive public health campaign that employs some stigmatization of obesity.
“Enhanced, Edgier”: A Euphemism for “Shame and Embarrassment”?
Authors: Gostin Lawrence O.
Published: October 2014

One of six commentaries on “Obesity: Chasing an Elusive Epidemic,” by Daniel Callahan, from the January‐February 2013 issue.
Obesity and Blame: Elusive Goals for Personal Responsibility
Authors: Schmidt Harald
Published: October 2014

One of six commentaries on “Obesity: Chasing an Elusive Epidemic,” by Daniel Callahan, from the January‐February 2013 issue.
The Author Replies
Authors: Callahan Daniel
Published: October 2014

A reply by the author of “Obesity: Chasing an Elusive Epidemic” to
Patient and Trainee: Learning When to Step In
Authors: Cummings Christy L.
Published: October 2014

With advancing rank in medical training comes increased academic and clinical responsibility, including education and supervision of trainees and junior staff. When I became a senior postdoctoral fellow sub‐specializing in neonatology, I assumed the role of co‐attending in the neonatal intensive care unit. At that point in my training, I felt well prepared for the challenging task. I would be in charge, make decisions independently with the team, and supervise, as well as teach, the junior fellows, residents, and practitioners. In short, I would assume full responsibility for the care of the patients, their families, and the medical team. My mentor, an experienced attending, would discuss every patient with me each day, but would otherwise stand in the shadows, available for help and guidance when needed.

On the very first day, one of the smaller premature babies on our service started having difficulty breathing, and it was soon clear that she would need to have her endotracheal tube reinserted.