bluuebunny/crossref_metadata_2025 huggingface dataset:
How to make a sterile helper
Authors: Downing Philip A. , Cornwallis Charlie K. , Griffin Ashleigh S.
Published: November 2016

The sterile worker castes found in the colonies of social insects are often cited as archetypal examples of altruism in nature. The challenge is to explain why losing the ability to mate has evolved as a superior strategy for transmitting genes into future generations. We propose that two conditions are necessary for the evolution of sterility: completely overlapping generations and monogamy. A review of the literature indicates that when these two conditions are met we consistently observe the evolution of sterile helpers. We explain the theory and evidence behind these ideas, and discuss the importance of ecology in predicting whether sterility will evolve using examples from social birds, mammals, and insects. In doing so, we offer an explanation for the extraordinary lifespans of some cooperative species which hint at ways in which we can unlock the secrets of long life.
Estimating hazard ratios in cohort data with missing disease information due to death
Authors: Binder Nadine , Herrnböck Anne‐Sophie , Schumacher Martin
Published: November 2016

In clinical and epidemiological studies information on the primary outcome of interest, that is, the disease status, is usually collected at a limited number of follow‐up visits. The disease status can often only be retrieved retrospectively in individuals who are alive at follow‐up, but will be missing for those who died before. Right‐censoring the death cases at the last visit (ad‐hoc analysis) yields biased hazard ratio estimates of a potential risk factor, and the bias can be substantial and occur in either direction. In this work, we investigate three different approaches that use the same likelihood contributions derived from an illness‐death multistate model in order to more adequately estimate the hazard ratio by including the death cases into the analysis: a parametric approach, a penalized likelihood approach, and an imputation‐based approach. We investigate to which extent these approaches allow for an unbiased regression analysis by evaluating their performance in simulation studies and on a real data example. In doing so, we use the full cohort with complete illness‐death data as reference and artificially induce missing information due to death by setting discrete follow‐up visits. Compared to an ad‐hoc analysis, all considered approaches provide less biased or even unbiased results, depending on the situation studied. In the real data example, the parametric approach is seen to be too restrictive, whereas the imputation‐based approach could almost reconstruct the original event history information.
Analyzing large datasets with bootstrap penalization
Authors: Fang Kuangnan , Ma Shuangge
Published: November 2016

Data with a largep(number of covariates) and/or a largen(sample size) are now commonly encountered. For many problems, regularization especially penalization is adopted for estimation and variable selection. The straightforward application of penalization to large datasets demands a “big computer” with high computational power. To improve computational feasibility, we develop bootstrap penalization, which dissects a big penalized estimation into a set of small ones, which can be executed in a highly parallel manner and each only demands a “small computer”. The proposed approach takes different strategies for data with different characteristics. For data with a largepbut a small to moderaten, covariates are first clustered into relatively homogeneous blocks. The proposed approach consists of two sequential steps. In each step and for each bootstrap sample, we select blocks of covariates and run penalization. The results from multiple bootstrap samples are pooled to generate the final estimate. For data with a largenbut a small to moderatep, we bootstrap a small number of subjects, apply penalized estimation, and then conduct a weighted average over multiple bootstrap samples. For data with a largepand a largen, the natural marriage of the previous two methods is applied. Numerical studies, including simulations and data analysis, show that the proposed approach has computational and numerical advantages over the straightforward application of penalization. An R package has been developed to implement the proposed methods.
Lone‐Actor Terrorist Target Choice
Authors: Gill Paul , Corner Emily
Published: November 2016

Lone‐actor terrorist attacks have risen to the forefront of the public's consciousness in the past few years. Some of these attacks were conducted against public officials. The rise of hard‐to‐detect, low‐tech attacks may lead to more public officials being targeted. This paper explores whether different behavioral traits are apparent within a sample of lone‐actor terrorists who plotted against high‐value targets (including public officials) than within a sample of lone actors who plotted against members of the public. Utilizing a unique dataset of 111 lone‐actor terrorists, we test a series of hypotheses related to attack capability and operational security. The results indicate that very little differentiates those who attack high‐value targets from those who attack members of the public. We conclude with a series of illustrations to theorize why this may be the case. Copyright © 2016 John Wiley & Sons, Ltd.
MFI Acid Catalysts with Different Crystal Sizes and Porosity for the Conversion of Furanic Compounds in Alcohol Media
Authors: Antunes Margarida M. , Lima Sérgio , Fernandes Auguste , Magalhães Ana L. , Neves Patrícia , Silva Carlos M. , Ribeiro Maria F. , Chadwick David , Hellgardt Klaus , Pillinger Martyn , Valente Anabela A.
Published: November 2016

Solid acid catalysts possessing MFI topology and different crystal sizes and porosities were explored for the conversion of carbohydrate‐biomass‐derived α‐angelica lactone and 5‐(hydroxymethyl)furfural, in 1‐butanol at T=120–170 °C, to give levulinate esters and furanic ethers. Micro/mesoporous microcrystalline catalysts were prepared by post‐synthesis base/acid treatments of ZSM‐5 zeolite; the influence of the desilication (base) conditions on the material properties was investigated. A nanocrystalline ZSM‐5 sample was synthesised by using hydrothermal, dynamic conditions and used as a reference material. A comparison of the catalytic performances of materials featuring different morphological, textural, and acid properties highlights a complex interplay between the acid and textural properties. The best‐performing catalyst (MZS0.6) was obtained by post‐synthesis‐treatment; fairly good catalytic stability was confirmed by catalyst recycling, contact tests, and characterisation of the spent catalyst. MZS0.6 was compared with the macrorecticular ion‐exchange resin Amberlyst‐15, chosen as a benchmark solid acid catalyst, in the two reaction systems.
Catalytically Triggered Energy Release from Strained Organic Molecules: The Surface Chemistry of Quadricyclane and Norbornadiene on Pt(111)
Authors: Bauer Udo , Mohr Susanne , Döpper Tibor , Bachmann Philipp , Späth Florian , Düll Fabian , Schwarz Matthias , Brummel Olaf , Fromm Lukas , Pinkert Ute , Görling Andreas , Hirsch Andreas , Bachmann Julien , Steinrück Hans‐Peter , Libuda Jörg , Papp Christian
Published: November 2016

We have investigated the surface chemistry of the polycyclic valence‐isomer pair norbornadiene (NBD) and quadricyclane (QC) on Pt(111). The NBD/QC system is considered to be a prototype for energy storage in strained organic compounds. By using a multimethod approach, including UV photoelectron, high‐resolution X‐ray photoelectron, and IR reflection–absorption spectroscopic analysis and DFT calculations, we could unambiguously identify and differentiate between the two molecules in the multilayer phase, which implies that the energy‐loaded QC molecule is stable in this state. Upon adsorption in the (sub)monolayer regime, the different spectroscopies yielded identical spectra for NBD and QC at 125 and 160 K, when multilayer desorption takes place. This behavior is explained by a rapid cycloreversion of QC to NBD upon contact with the Pt surface. The NBD adsorbs in a η2:η1 geometry with an agostic Pt−H interaction of the bridgehead CH2 subunit and the surface. Strong spectral changes are observed between 190 and 220 K because the hydrogen atom that forms the agostic bond is broke. This reaction yields a norbornadienyl intermediate species that is stable up to approximately 380 K. At higher temperatures, the molecule dehydrogenates and decomposes into smaller carbonaceous fragments.
“Bis‐Click” Ligation of DNA: Template‐Controlled Assembly, Circularisation and Functionalisation with Bifunctional and Trifunctional Azides
Authors: Yang Haozhe , Seela Frank
Published: November 2016

Ligation and circularisation of oligonucleotides containing terminal triple bonds was performed with bifunctional or trifunctional azides. Both reactions are high yielding. Template‐assisted bis‐click ligation of two individual non‐complementary oligonucleotide strands was accomplished to yield heterodimers exclusively. In this context, the template fulfils two functions: it accelerates the ligation reaction and controls product assembly (heterodimer vs. homodimer formation). Intermolecular bis‐click circularisation of one oligonucleotide strand took place without template assistance. For construction of oligonucleotides with terminal triple bonds in the nucleobase side chain, 7‐ or 5‐functionalised 7‐deaza‐dA and dU residues were used. These oligonucleotides are directly accessible by solid‐phase synthesis. When trifunctional azides were employed instead of bifunctional linkers, functionalisation of the remaining azido group was performed with small molecules such as 1‐ethynyl pyrene, biotin propargyl amide or with ethynylated oligonucleotides. By this means, branched DNA was constructed.
Cure rate quantile regression accommodating both finite and infinite survival times
Authors: Wu Yuanshan , Yin Guosheng
Published: November 2016

In survival analysis a proportion of patients may be cured by the treatment, and thus they become risk‐free of the event of interest and their survival times change to infinity. The existence of such a survival fraction often makes the underlying population more heterogeneous and heavily right‐skewed. Compared with the traditional mean‐ or hazard‐based regression methods, quantile regression is more suitable for such survival data as it is more robust against outliers or infinite survival times. Moreover, it offers a comprehensive assessment of the covariate effects on the survival times at different quantile levels. We propose a new cure rate quantile regression model for the entire population including both finite and infinite survival times. By invoking non‐parametric functional estimation an iterative algorithm is developed to estimate the cure rate parameters. The scheme of redistribution‐of‐mass to the right for censored data is adopted to estimate the quantile regression parameters. The consistency and asymptotic normality of the proposed estimators are established. Extensive simulation studies are conducted to evaluate the finite‐sample performance of the proposed method, which is further illustrated with a phase III melanoma clinical trial study.The Canadian Journal of Statistics45: 29–43; 2017 © 2016 Statistical Society of Canada
In vivo transgenic expression of collybistin in neurons of the rat cerebral cortex
Authors: Fekete Christopher D. , Goz Roman U. , Dinallo Sean , Miralles Celia P. , Chiou Tzu‐Ting , Bear John , Fiondella Christopher G. , LoTurco Joseph J. , De Blas Angel L.
Published: November 2016

Collybistin (CB) is a guanine nucleotide exchange factor selectively localized to γ‐aminobutyric acid (GABA)ergic and glycinergic postsynapses. Active CB interacts with gephyrin, inducing the submembranous clustering and the postsynaptic accumulation of gephyrin, which is a scaffold protein that recruits GABAA receptors (GABAARs) at the postsynapse. CB is expressed with or without a src homology 3 (SH3) domain. We have previously reported the effects on GABAergic synapses of the acute overexpression of CBSH3− or CBSH3+ in cultured hippocampal (HP) neurons. In the present communication, we are studying the effects on GABAergic synapses after chronic in vivo transgenic expression of CB2SH3− or CB2SH3+ in neurons of the adult rat cerebral cortex. The embryonic precursors of these cortical neurons were in utero electroporated with CBSH3− or CBSH3+ DNAs, migrated to the appropriate cortical layer, and became integrated in cortical circuits. The results show that: 1) the strength of inhibitory synapses in vivo can be enhanced by increasing the expression of CB in neurons; and 2) there are significant differences in the results between in vivo and in culture studies. J. Comp. Neurol. 525:1291–1311, 2017. © 2016 Wiley Periodicals, Inc.
Cellular localization of relaxin‐like gonad‐stimulating peptide expression in Asterias rubens: New insights into neurohormonal control of spawning in starfish
Authors: Lin Ming , Mita Masatoshi , Egertová Michaela , Zampronio Cleidiane G. , Jones Alexandra M. , Elphick Maurice R.
Published: November 2016

Gamete maturation and spawning in starfish is triggered by a gonad‐stimulating substance (GSS), which is present in extracts of the radial nerve cords. Purification of GSS from the starfish Patiria pectinifera identified GSS as a relaxin‐like polypeptide, which is now known as relaxin‐like gonad‐stimulating peptide (RGP). Cells expressing RGP in the radial nerve cord of P. pectinifera have been visualized, but the presence of RGP‐expressing cells in other parts of the starfish body has not been investigated. Here we addressed this issue in the starfish Asterias rubens. An A. rubens RGP (AruRGP) precursor cDNA was sequenced and the A chain and B chain that form AruRGP were detected in A. rubens radial nerve cord extracts using mass spectrometry. Comparison of the bioactivity of AruRGP and P. pectinifera RGP (PpeRGP) revealed that both polypeptides induce oocyte maturation and ovulation in A. rubens ovarian fragments, but AruRGP is more potent than PpeRGP. Analysis of the expression of AruRGP in A. rubens using mRNA in situ hybridization revealed cells expressing RGP in the radial nerve cords, circumoral nerve ring, and tube feet. Furthermore, a band of RGP‐expressing cells was identified in the body wall epithelium lining the cavity that surrounds the sensory terminal tentacle and optic cushion at the tips of the arms. Discovery of these RGP‐expressing cells closely associated with sensory organs in the arm tips is an important finding because these cells are candidate physiological mediators for hormonal control of starfish spawning in response to environmental cues. J. Comp. Neurol. 525:1599–1617, 2017. © 2016 Wiley Periodicals, Inc.
Remarkable Solvatofluorochromism of a [2.2]Paracyclophane‐Containing Organoboron Complex: A Large Stokes Shift Promoted by Excited State Intramolecular Charge Transfer
Authors: Tanaka Mirai , Muraoka Shunsuke , Matsui Yasunori , Ohta Eisuke , Sakai Atsushi , Ogaki Takuya , Yoshimoto Yuichi , Mizuno Kazuhiko , Ikeda Hiroshi
Published: November 2016

An organoboron complex containing a [2.2]paracyclophanyl group (2 BF2) exhibits remarkable solvatofluorochromism associated with a large Stokes shift. With increased solvent polarity, the fluorescence (FL) color of 2 BF2 changes from sky blue (λFL=485 nm in cyclohexane (c‐C6H12)) to orange (λFL=576 nm in CH3CN). This behavior derives from the intramolecular charge transfer (ICT) character of the excited state 2 BF2* in which the [2.2]paracyclophanyl group serves as the electron donor while the remaining 2 BF2 structure (apart from the sub‐benzene ring) functions as the electron acceptor. Wave deconvolution of FL spectra in a solvent mixture of CH2Cl2/c‐C6H12, and a plot of the FL emission energy versus the CH2Cl2/c‐C6H12 ratio, suggest that FL of 2 BF2 occurs from two types of 2 BF2* excited states. The results of DFT calculations support this explanation and further emphasize that the ICT character of 2 BF2* is derived from a large conformational change associated with the electron‐donating character of the [2.2]paracyclophanyl group. Moreover, the fact that 2 BF2 is more sensitive than Reichardt's dye to polarity changes in a low polarity CH2Cl2/c‐C6H12 solvent mixture is also of importance.
Surface Electrochemical Modification of a Nickel Substrate to Prepare a NiFe‐based Electrode for Water Oxidation
Authors: Guo Dingyi , Qi Jing , Zhang Wei , Cao Rui
Published: November 2016

The slow kinetics of water oxidation greatly jeopardizes the efficiency of water electrolysis for H2 production. Developing highly active water oxidation electrodes with affordable fabrication costs is thus of great importance. Herein, a NiIIFeIII surface species on Ni metal substrate was generated by electrochemical modification of Ni in a ferrous solution by a fast, simple, and cost‐effective procedure. In the prepared NiIIFeIII catalyst film, FeIII was incorporated uniformly through controlled oxidation of FeII cations on the electrode surface. The catalytically active NiII originated from the Ni foam substrate, which ensured the close contact between the catalyst and the support toward improved charge‐transfer efficiency. The as‐prepared electrode exhibited high activity and long‐term stability for electrocatalytic water oxidation. The overpotentials required to reach water oxidation current densities of 50, 100, and 500 mA cm−2 are 276, 290, and 329 mV, respectively.
Current and future ozone risks to global terrestrial biodiversity and ecosystem processes
Authors: Fuhrer Jürg , Val Martin Maria , Mills Gina , Heald Colette L. , Harmens Harry , Hayes Felicity , Sharps Katrina , Bender Jürgen , Ashmore Mike R.
Published: November 2016

Risks associated with exposure of individual plant species to ozone (O3) are well documented, but implications for terrestrial biodiversity and ecosystem processes have received insufficient attention. This is an important gap because feedbacks to the atmosphere may change as future O3 levels increase or decrease, depending on air quality and climate policies. Global simulation of O3 using the Community Earth System Model (CESM) revealed that in 2000, about 40% of the Global 200 terrestrial ecoregions (ER) were exposed to O3 above thresholds for ecological risks, with highest exposures in North America and Southern Europe, where there is field evidence of adverse effects of O3, and in central Asia. Experimental studies show that O3 can adversely affect the growth and flowering of plants and alter species composition and richness, although some communities can be resilient. Additional effects include changes in water flux regulation, pollination efficiency, and plant pathogen development. Recent research is unraveling a range of effects belowground, including changes in soil invertebrates, plant litter quantity and quality, decomposition, and nutrient cycling and carbon pools. Changes are likely slow and may take decades to become detectable. CESM simulations for 2050 show that O3 exposure under emission scenario RCP8.5 increases in all major biomes and that policies represented in scenario RCP4.5 do not lead to a general reduction in O3 risks; rather, 50% of ERs still show an increase in exposure. Although a conceptual model is lacking to extrapolate documented effects to ERs with limited or no local information, and there is uncertainty about interactions with nitrogen input and climate change, the analysis suggests that in many ERs, O3 risks will persist for biodiversity at different trophic levels, and for a range of ecosystem processes and feedbacks, which deserves more attention when assessing ecological implications of future atmospheric pollution and climate change.
Ecological monitoring and evidence‐based decision‐making in America's National Parks: highlights of the Special Feature
Authors: Rodhouse Thomas J. , Sergeant Christopher J. , Schweiger E. William
Published: November 2016

In this Special Feature, we celebrate 100 years of National Park Service science by highlighting contributions from the agency's Inventory and Monitoring Division. This broad body of work coalesces into several themes, including the role of protected areas in understanding rapid global change and the growing interest in place‐based ecological insights that contextualize scientific information from protected areas across broader scales. Finally, we illustrate progress on the long‐sought integration of science into the resource management strategies implemented within “America's Best Idea,” now more important than ever given the many challenges our nation's parks face.
Phenotypic plasticity of nest timing in a post‐glacial landscape: how do reptiles adapt to seasonal time constraints?
Authors: Edge Christopher B. , Rollinson Njal , Brooks Ronald J. , Congdon Justin D. , Iverson John B. , Janzen Fredric J. , Litzgus Jacqueline D.
Published: November 2016

Life histories evolve in response to constraints on the time available for growth and development. Nesting date and its plasticity in response to spring temperature may therefore be important components of fitness in oviparous ectotherms near their northern range limit, as reproducing early provides more time for embryos to complete development before winter. We used data collected over several decades to compare air temperature and nest date plasticity in populations of painted turtles and snapping turtles from a relatively warm environment (southeastern Michigan) near the southern extent of the last glacial maximum to a relatively cool environment (central Ontario) near the northern extent of post‐glacial recolonization. For painted turtles, population‐level differences in reaction norm elevation for two phenological traits were consistent with adaptation to time constraints, but no differences in reaction norm slopes were observed. For snapping turtle populations, the difference in reaction norm elevation for a single phenological trait was in the opposite direction of what was expected under adaptation to time constraints, and no difference in reaction norm slope was observed. Finally, among‐individual variation in individual plasticity for nesting date was detected only in the northern population of snapping turtles, suggesting that reaction norms are less canalized in this northern population. Overall, we observed evidence of phenological adaptation, and possibly maladaptation, to time constraints in long‐lived reptiles. Where present, (mal)adaptation occurred by virtue of differences in reaction norm elevation, not reaction norm slope. Glacial history, generation time, and genetic constraint may all play an important role in the evolution of phenological timing and its plasticity in long‐lived reptiles.
Above‐ and belowground insect herbivory modifies the response of a grassland plant community to nitrogen eutrophication
Authors: Borgström Pernilla , Strengbom Joachim , Marini Lorenzo , Viketoft Maria , Bommarco Riccardo
Published: November 2016

Understanding the role that species interactions play in determining the rate and direction of ecosystem change due to nitrogen (N) eutrophication is important for predicting the consequences of global change. Insects might play a major role in this context. They consume substantial amounts of plant biomass and can alter competitive interactions among plants, indirectly shaping plant community composition. Nitrogen eutrophication affects plant communities globally, but there is limited experimental evidence of how insect herbivory modifies plant community response to raised N levels. Even less is known about the roles of above‐ and belowground herbivory in shaping plant communities, and how the interaction between the two might modify a plant community's response to N eutrophication. We conducted a 3‐yr field experiment where grassland plant communities were subjected to above‐ and belowground insect herbivory with and without N addition, in a full‐factorial design. We found that herbivory modified plant community responses to N addition. Aboveground herbivory decreased aboveground plant community biomass by 21%, but only at elevated N. When combined, above‐ and belowground herbivory had a stronger negative effect on plant community biomass at ambient N (11% decrease) than at elevated N (4% decrease). In addition, herbivory shifted the functional composition of the plant community, and the magnitude of the shifts depended on the N level. The N and herbivory treatments synergistically conferred a competitive advantage to forbs, which benefited when both herbivory types were present at elevated N. Evenness among the plant species groups increased when aboveground herbivory was present, but N addition attenuated this increase. Our results demonstrate that a deeper understanding of how plant–herbivore interactions above and below ground shape the composition of a plant community is crucial for making reliable predictions about the ecological consequences of global change.
The role of competition, ecotones, and temperature in the elevational distribution of Himalayan birds
Authors: Elsen Paul R. , Tingley Morgan W. , Kalyanaraman Ramnarayan , Ramesh Krishnamurthy , Wilcove David S.
Published: November 2016

There is clear evidence that species’ ranges along environmental gradients are constrained by both biotic and abiotic factors, yet their relative importance in structuring realized distributions remains uncertain. We surveyed breeding bird communities while collecting in situ temperature and vegetation data along five elevational transects in the Himalayas differing in temperature variability, habitat zonation, and bird richness in order to disentangle temperature, habitat, and congeneric competition as mechanisms structuring elevational ranges. Our results from species’ abundance models representing these three mechanisms differed markedly from previous, foundational research in the tropics. Contrary to general expectations, we found little evidence for competition as a major determinant of range boundaries, with congeneric species limiting only 12% of ranges. Instead, temperature and habitat were found to structure the majority of species’ distributions, limiting 48 and 40% of ranges, respectively. Our results suggest that different mechanisms may structure species ranges in the temperate Himalayas compared to tropical systems. Despite recent evidence suggesting temperate species have broader thermal tolerances than tropical species, our findings reinforce the notion that the abiotic environment has significant control over the distributions of temperate species.
Health Care for NFL Players: Upholding Physician Standards and Enhancing the Doctor‐Patient Relationship
Authors: Duvernay‐Tardif Laurent
Published: November 2016

Beginning my third year with the Kansas City Chiefs and being also a medical student at McGill University, I was at first a little reluctant to comment on Glenn Cohen et al.’s critique of the National Football League's structure involving player health and team doctors, but the opportunity to provide a perspective as both a football player and a medical student was too much to forgo. Because of my athletic and academic background, I am often asked what I think about injuries in professional sports and about the role of sports medicine physicians, and Cohen et al.’s article demands a thoughtful reaction. I want to suggest that the fundamental principles concerning the medical profession and the doctor‐patient relationship provide additional arguments for some of the solutions that Cohen et al. discuss. The professional self‐regulation that the proposed medical committee could provide and the reliance on a doctor who was not hired by the player's employer—the club—for a second opinion are both good ways to minimize conflicts of interest.
Being Right Isn't Always Enough: NFL Culture and Team Physicians’ Conflict of Interest
Authors: McKinney Ross
Published: November 2016

The job of being a sports team physician is difficult, regardless of the level, from high school to the National Football League. When a sports league receives the intensity of attention leveled at the NFL, though, a difficult occupation becomes even more challenging. Even for the NFL players themselves, players’ best interests regarding health issues are often unclear. Football players are, as a lot, highly competitive individuals. They want to win, and they want to help the team win. It's a warrior culture, and respect is earned by playing hurt. Should the team physician respect a player's autonomy when this means allowing him to make choices that might lead to further personal harm, especially if the player's choices align with the preference of the coach and management? Or should the doctor set limits and balance the player's choices with a paternalistic set of constraints, perhaps in opposition to both the player's and the team's desires? Simplification of this web of conflicts of interest is the goal of the model proposed by Glenn Cohen, Holly Lynch, and Christopher Deubert. In my view, their proposal is very clever. As an idea, it meets the expectations its authors set, namely, to minimize the problem of conflict of interest in the delivery of health care services to NFL football players. The ethics of the proposal align well with certain moral goals, like treating the player's interests more fairly and treating the player's health as an end instead of as the means to an end. But will such a proposal ever make headway in the pressurized environment of the NFL?
Preventing Conflicts of Interest of NFL Team Physicians
Authors: Rothstein Mark A.
Published: November 2016

At least since the time of Hippocrates, the physician‐patient relationship has been the paradigmatic ethical arrangement for the provision of medical care. Yet, a physician‐patient relationship does not exist in every professional interaction involving physicians and individuals they examine or treat. There are several “third‐party” relationships, mostly arising where the individual is not a patient and is merely being examined rather than treated, the individual does not select or pay the physician, and the physician's services are provided for the benefit of another party. Physicians who treat NFL players have a physician‐patient relationship, but physicians who merely examine players to determine their health status have a third‐party relationship. As described by Glenn Cohen et al., the problem is that typical NFL team doctors perform both functions, which leads to entrenched conflicts of interest. Although there are often disputes about treatment, the main point of contention between players and team physicians is the evaluation of injuries and the reporting of players’ health status to coaches and other team personnel. Cohen et al. present several thoughtful recommendations that deserve serious consideration. Rather than focusing on their specific recommendations, however, I would like to explain the rationale for two essential reform principles: the need to sever the responsibilities of treatment and evaluation by team physicians and the need to limit the amount of player medical information disclosed to teams.
The Dual Role of NFL Team Doctors
Authors: Washington Marvin
Published: November 2016

Glenn Cohen, Holly Fernandez Lynch, and Christopher Deubert are right in their article “A Proposal to Address NFL Club Doctors’ Conflicts of Interest and to Promote Player Trust” that the problem with the medical care rendered to National Football League players is not that the doctors are bad, but that the system in which they provide care is structured badly. We saw some of the problems this system causes last season in what happened to Case Kenum, a quarterback for the Los Angeles Rams who, despite having a possible concussion from a game injury, was allowed to continue to play, with a concussion spotter in the booth and coaches, teammates, seven game officials, and two full training staffs present. From my experience playing in the league from 1989 to 1999, I do not believe that you can eliminate the conflict of interest completely, but I think it can be limited to the point that it does not harm the player. As the structure is now, with the team paying the club doctor, it is impossible to put the players’ health and well‐being before the team's on‐field priorities.
Assessing the reliability of ecotoxicological studies: An overview of current needs and approaches
Authors: Moermond Caroline , Beasley Amy , Breton Roger , Junghans Marion , Laskowski Ryszard , Solomon Keith , Zahner Holly
Published: November 2016

In general, reliable studies are well designed and well performed, and enough details on study design and performance are reported to assess the study. For hazard and risk assessment in various legal frameworks, many different types of ecotoxicity studies need to be evaluated for reliability. These studies vary in study design, methodology, quality, and level of detail reported (e.g., reviews, peer-reviewed research papers, or industry-sponsored studies documented under Good Laboratory Practice [GLP] guidelines). Regulators have the responsibility to make sound and verifiable decisions and should evaluate each study for reliability in accordance with scientific principles regardless of whether they were conducted in accordance with GLP and/or standardized methods. Thus, a systematic and transparent approach is needed to evaluate studies for reliability. In this paper, 8 different methods for reliability assessment were compared using a number of attributes: categorical versus numerical scoring methods, use of exclusion and critical criteria, weighting of criteria, whether methods are tested with case studies, domain of applicability, bias toward GLP studies, incorporation of standard guidelines in the evaluation method, number of criteria used, type of criteria considered, and availability of guidance material. Finally, some considerations are given on how to choose a suitable method for assessing reliability of ecotoxicity studies. Integr Environ Assess Manag 2017;13:640–651. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

When evaluating the reliability of an ecotoxicity study or individual effect values from this study, a systematic and transparent assessment method is critical to ensure an unbiased and consistent categorization of reliability. Eight different methods for reliability assessment were compared using a number of attributes. Some additional considerations are given on how to choose a suitable method for assessing reliability of ecotoxicity studies.
Prediagnostic circulating concentrations of plasma insulin‐like growth factor‐I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition
Authors: Perez‐Cornago Aurora , Appleby Paul N. , Tipper Sarah , Key Timothy J. , Allen Naomi E. , Nieters Alexandra , Vermeulen Roel , Roulland Sandrine , Casabonne Delphine , Kaaks Rudolf , Fortner Renee T. , Boeing Heiner , Trichopoulou Antonia , La Vecchia Carlo , Klinaki Eleni , Hansen Louise , Tjønneland Anne , Bonnet Fabrice , Fagherazzi Guy , Boutron‐Ruault Marie‐Christine , Pala Valeria , Masala Giovanna , Sacerdote Carlotta , Peeters Petra H. , Bueno‐de‐Mesquita H. B(as) , Weiderpass Elisabete , Dorronsoro Miren , Quirós J. Ramón , Barricarte Aurelio , Gavrila Diana , Agudo Antonio , Borgquist Signe , Rosendahl Ann H. , Melin Beatrice , Wareham Nick , Khaw Kay‐Tee , Gunter Marc , Riboli Elio , Vineis Paolo , Travis Ruth C.
Published: November 2016

Insulin‐like growth factor (IGF)‐I has cancer promoting activities. However, the hypothesis that circulating IGF‐I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF‐I concentration was measured in pre‐diagnostic plasma samples from a nested case–control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF‐I concentration was not associated with overall lymphoma risk (multivariable‐adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57–1.03], ptrend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF‐I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all ≥ 0.05). There were no associations between IGF‐I concentration and risk for specific BCL subtypes, T‐cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF‐I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF‐I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF‐I concentrations with lymphoma subtypes.
False and mycoplasma‐contaminated leukemia–lymphoma cell lines: time for a reappraisal
Authors: Drexler Hans G. , Dirks Wilhelm G. , MacLeod Roderick A.F. , Uphoff Cord C.
Published: November 2016

Leukemia–lymphoma cell lines are important research tools in a variety of fields. To represent adequate model systems it is of utmost importance that cell lines faithfully model the primary tumor material and are not cross‐contaminated with unrelated cell material (or contaminated with mycoplasma). As it has been previously reported that cross‐contaminated cell lines represent a significant problem, it is of interest to know whether any improvement in the prevalence of such “false cell lines” had occurred since we called the alert in 1999. A retrospective review of our data archives covered 848 cell lines received from 1990 to 2014 from 290 laboratories in 23 countries spanning the spectrum of leukemia–lymphoma entities. Two variables were considered: authenticity and freedom from mycoplasma infection. Regarding provenance, we separately considered primary sources (original investigators having established the cell lines or reference repositories) and secondary sources. The percentages of mycoplasma‐contaminated cell lines decreased significantly over the 25‐year timespan. Among primary sourced material: mycoplasma‐contamination fell from 23% to 0%; among secondary sourced: from 48% to 21%. The corresponding figures for cross‐contamination declined from 15% to 6%, while among material obtained from secondary sources prevalence remained remarkably high, throughout the time periods at 14–18%. Taken together, our data indicate that using non‐authenticated cell lines from secondary sources carries a risk of about 1:6 for obtaining a false cell line. The use of authentic leukemia–lymphoma cell lines holds important translational value for their model character and the reproducibility of the laboratory data in the clinical arena.
SYSTEMS OF SYSTEMS: WHY THEY MATTER TO ALL SYSTEMS ENGINEERS
Authors: Cook Stephen
Published: November 2016

Systems of systems (SoS) abound around us. This paper opens by introducing SoS and systems of systems engineering (SoSE) in a descriptive way and addresses why they are important to all systems engineers. This special issue was coordinated by the INCOSE Systems of Systems Working Group (SoSWG) and we explain how we set out to convey the key ideas in SoSE to all systems engineering practitioners regardless of their previous exposure to SoS. An introduction to the companion papers follows and in an effort to reinforce that SoSE is a class of engineering, the article concludes with a salient reminder of what can happen when engineering becomes relegated over time.
SOME APPROACHES TO SYSTEMS OF SYSTEMS ENGINEERING
Authors: Cook Stephen
Published: November 2016

Given the wide span of challenges that are amenable to systems of systems engineering (SoSE), it is not surprising that there are a considerable number of rather different SoSE approaches in use. The paper opens by describing the generic nature of SoSE methodologies and argues that they should be value‐driven, incremental, socio‐technical, bespoke for each system of systems (SoS) problem, achieve their effect through influence and persuasion rather than control, and should be informed by evidence of what works in practice. The body of the paper describes three SoSE approaches and comments on the classes of SoS for which they have proved to be successful.
THE SYSTEM OF SYSTEMS APPROACH (SOSA)
Authors: Coffield Billy
Published: November 2016

There are number of ways in which organisations have chosen to manage their system of systems (SoS) which suits their business environment and particular SoS challenges. The system of systems approach (SOSA) is in response to the challenges presented by an increasingly complex capability design, acquisition and operating environment. The SOSA represents the way in which UK Defence applies systems engineering and systems approaches best practice in order to achieve effective and affordable military capability.

In view of the need to maximise the agility and flexibility of a smaller armed forces to meet a wide range of possible operational scenarios and commitments, as captured in Defence Strategic Direction 2016. Rather than defining specific SoS requirements to meet a distinct purpose, the MOD has chosen to manage its SoS by maximising the SoS attributes such as interoperability, openness, commonality, reusability and coherence.
ARCHITECTURAL MODELLING PATTERNS FOR SYSTEMS OF SYSTEMS
Authors: Claire Ingram , Richard Payne , John Fitzgerald
Published: November 2016

Architectural properties are amongst the defining features of systems of systems (SoS) – including distribution of the constituent parts, their autonomy, long lifecycles and unsynchronized evolution. In addition, SoS engineers need to consider the integration of legacy constituent parts, reason about the emergent behaviour of the SoS, determine the level of centralised control, and support resilience and fault tolerance. These are all features which can be tackled at least partially through architectural patterns. In this article, we present three example patterns previously identified in SoS. Patterns like these can also be used as a mechanism for transferring lessons learned in one SoS application domain into another domain. For each pattern presented, we highlight features that address the challenges posed by SoS. Finally, we detail ongoing efforts with the INCOSE Systems of Systems and Patterns Working Groups to prioritise future work in this area.
Runx1 Orchestrates Sphingolipid Metabolism and Glucocorticoid Resistance in Lymphomagenesis
Authors: Kilbey A. , Terry A. , Wotton S. , Borland G. , Zhang Q. , Mackay N. , McDonald A. , Bell M. , Wakelam M.J.O. , Cameron E.R. , Neil J.C.
Published: November 2016

The three‐membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumor suppressors and oncogenes. In mouse models, the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over‐expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the “sphingolipid rheostat” from ceramide to sphingosine‐1‐phosphate (S1P). Testing of this relationship in lymphoma cells was therefore a high priority. We find that ectopic expression of Runx1 in lymphoma cells consistently perturbs the sphingolipid rheostat, whereas an essential physiological role for Runx1 is revealed by reduced S1P levels in normal spleen after partial Cre‐mediated excision. Furthermore, we show that ectopic Runx1 expression confers increased resistance of lymphoma cells to glucocorticoid‐mediated apoptosis, and elucidate the mechanism of cross‐talk between glucocorticoid and sphingolipid metabolism through Sgpp1. Dexamethasone potently induces expression of Sgpp1 in T‐lymphoma cells and drives cell death which is reduced by partial knockdown of Sgpp1 with shRNA or direct transcriptional repression of Sgpp1 by ectopic Runx1. Together these data show that Runx1 plays a role in regulating the sphingolipid rheostat in normal development and that perturbation of this cell fate regulator contributes to Runx‐driven lymphomagenesis. J. Cell. Biochem. 118: 1432–1441, 2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
Computing infrared spectra of proteins using the exciton model
Authors: Husseini Fouad S. , Robinson David , Hunt Neil T. , Parker Anthony W. , Hirst Jonathan D.
Published: November 2016

The ability to compute from first principles the infrared spectrum of a protein in solution phase representing a biological system would provide a useful connection to atomistic models of protein structure and dynamics. Indeed, such calculations are a vital complement to 2DIR experimental measurements, allowing the observed signals to be interpreted in terms of detailed structural and dynamical information. In this article, we have studied nine structurally and spectroscopically well‐characterized proteins, representing a range of structural types. We have simulated the equilibrium conformational dynamics in an explicit point charge water model. Using the resulting trajectories based on MD simulations, we have computed the one and two dimensional infrared spectra in the Amide I region, using an exciton approach, in which a local mode basis of carbonyl stretches is considered. The role of solvent in shifting the Amide I band (by 30 to 50 cm−1) is clearly evident. Similarly, the conformational dynamics contribute to the broadening of peaks in the spectrum. The inhomogeneous broadening in both the 1D and 2D spectra reflects the significant conformational diversity observed in the simulations. Through the computed 2D cross‐peak spectra, we show how different pulse schemes can provide additional information on the coupled vibrations. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
The Role of Multiwall Carbon Nanotubes in Cu‐BTC Metal‐Organic Frameworks for CO2 Adsorption
Authors: Ullah Sami , Shariff Azmi Mohd. , Bustam Mohamad Azmi , Elkhalifah Ali Eltayeb Ibrahim , Gonfa Girma , Kareem Firas Ayad Abdul
Published: November 2016

The discovery of natural gas fields with a high content of CO2 in world gas reservoirs poses new challenges for CO2 capture. This work investigates the use of the metal‐organic framework (MOF) Cu‐BTC and hybrid MWCNTs@Cu‐BTC for CO2 adsorption. Cu‐BTC and hybrid MWCNTs@Cu‐BTC were synthesized by the solvothermal method. The results of imaging of intact MOF pores in Cu‐BTC and hybrid MWCNTs@Cu‐BTC nanocrystals by high‐resolution transmission electron microscopy (HRTEM) under liquid nitrogen conditions are presented. Physical characterizations of the solid adsorbents were made by using a selection of different techniques, including field‐emission scanning electron microscopy (FESEM), X‐ray powder diffraction (XRD), Fourier transform infrared (FT‐IR) spectroscopy, thermogravimetric analysis (TGA), Brunauer–Emmet–Teller (BET) surface area, and CO2 adsorption and physisorption measurements. HRTEM and FESEM confirmed that Cu‐BTC has an octahedral shape and that the surface morphology of Cu‐BTC changes by the intercalation of MWCTNs. The results show that the modified Cu‐BTC improved the CO2 adsorption compared to pure Cu‐BTC. The increase in the CO2 uptake capabilities of hybrid MWCNTs@Cu‐BTC was ascribed to the intercalation of MWCNTs with Cu‐BTC crystals. The CO2 sorption capacities of Cu‐BTC and hybrid MWCNTs@Cu‐BTC were found to increase from 1.91701 to 3.25642 mmol/g at ambient conditions.