bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting‐State Functional Connectivity and Cognition After Major Cardiac Surgery in Older Adults without Preoperative Cognitive Impairment: Preliminary Findings
Authors: Browndyke Jeffrey N. , Berger Miles , Harshbarger Todd B. , Smith Patrick J. , White William , Bisanar Tiffany L. , Alexander John H. , Gaca Jeffrey G. , Welsh‐Bohmer Kathleen , Newman Mark F. , Mathew Joseph P.
Published: November 2016

Objectives

To look for changes in intrinsic functional brain connectivity associated with postoperative changes in cognition, a common complication in seniors undergoing major surgery, using resting‐state functional magnetic resonance imaging.

Design

Objective cognitive testing and functional brain imaging were prospectively performed at preoperative baseline and 6 weeks after surgery and at the same time intervals in nonsurgical controls.

Setting

Academic medical center.

Participants

Older adults undergoing cardiac surgery (n = 12) and nonsurgical older adult controls with a history of coronary artery disease (n = 12); no participants had cognitive impairment at preoperative baseline (Mini‐Mental State Examination score >27).

Measurements

Differences in resting‐state functional connectivity (RSFC) and global cognitive change relationships were assessed using a voxel‐wise intrinsic connectivity method, controlling for demographic factors and pre‐ and perioperative cerebral white matter disease volume. Analyses were corrected for multiple comparisons (false discovery rate P < .01).

Results

Global cognitive change after cardiac surgery was significantly associated with intrinsic RSFC changes in regions of the posterior cingulate cortex and right superior frontal gyrus—anatomical and functional locations of the brain's default mode network (DMN). No statistically significant relationships were found between global cognitive change and RSFC change in nonsurgical controls.

Conclusion

Clinicians have long known that some older adults develop postoperative cognitive dysfunction (POCD) after anesthesia and surgery, yet the neurobiological correlates of POCD are not well defined. The current results suggest that altered RSFC in specific DMN regions is positively correlated with global cognitive change 6 weeks after cardiac surgery, suggesting that DMN activity and connectivity could be important diagnostic markers of POCD or intervention targets for potential POCD treatment efforts.
Consistency Matters in Formally Selecting Incremental and Radical New Product Ideas for Advancement
Authors: Eling Katrin , Griffin Abbie , Langerak Fred
Published: November 2016

Several new product development (NPD) scholars have argued that formal processes should be used when selecting incremental new product ideas for advancement at the very beginning of the fuzzy front end (FFE), but that such formal processes may be less beneficial when selecting radical new product ideas. However, arguments also exist for using formal idea selection processes for both types of new product ideas. In practice, informal processes are used for selecting both idea types and more formal processes are used for selecting radical ideas. Unequivocal empirical evidence for either of the opposing views or practices is lacking.

This study sheds light on this matter using data from 161 of the firms that participated in the Product Development and Management Association's latest (2012) Comparative Performance Assessment Study. The results reveal that the highest idea success rate (i.e., the proportion of selected ideas that are eventually launched as new products and are successful in the marketplace) is associated with firms’ use of formal processes to select the vast majority of both incremental and radical new product ideas for advancement. This finding supports earlier claims that even for (raw) idea selection processes that take place at the very beginning of the FFE, managers need to adopt a portfolio perspective and consistently use formal idea advancement selection processes to ensure attaining the right balance between radical and incremental projects in later stages of the NPD pipeline to enhance overall NPD success. Notably, this finding shows that common managerial practices of using inconsistent approaches for selecting radical and incremental ideas for advancement need to be reconsidered.
The Roles of Sustainability Orientation and Market Knowledge Competence in New Product Development Success
Authors: Claudy Marius C. , Peterson Mark , Pagell Mark
Published: November 2016

Firms’ sustainability orientation (SO) is widely understood as a strategic resource, which can lead to competitive advantage and superior (financial) performance. While recent empirical evidence suggests a moderate and positive relationship between SO and financial performance on a corporate level, little is understood about the influence of SO on new product development (NPD) success. Building on the natural‐resource‐based view (NRBV) of the firm, we hypothesize that firms’ SO positively influences NPD success, because of efficiency gains and differentiation advantages. However, scholars have also argued that the win–win paradigm postulated by NRBV might not always hold because NPD managers might find it difficult to balance sustainability objectives with the needs of their customer and the competitive dynamics in their markets. It is, therefore, proposed that market knowledge competence (MKC) is an important capability, which helps firms to balance social and ecological objectives with economic goals such as profitability and market share. Using data from 343 international firms from 24 countries that was collected by the Product Development and Management Association, structural equation modeling results suggest that (1) SO positively influences NPD and that (2) this relationship is partially mediated by firms’ market knowledge capabilities. The findings suggest that strategic‐level SO and MKC are complementary in that they help in balancing trade‐offs between sustainaility objectives and profitability goals. In this way, the study contributes to a better understanding of how critical NPD practices can help managers to translate firms’ SO into NPD success. The article concludes by highlighting implications for product innovation managers.
Public Interest Law Organizations and the Two-Tier System of Access to Justice in the United States
Authors: Albiston Catherine , Li Su , Beth Nielsen Laura
Published: November 2016

Public interest law organizations (PILOs) are important institutions for providing access to justice in the United States. How have political, economic, and institutional factors shaped PILOs? How do PILOs vary in the services they offer and in their geographical location relative to poverty and population in the United States? This article investigates these questions by combining original survey data from a representative sample of public interest law organizations with GIS data on population and poverty. We find that the presence of a PILO is positively related to political progressiveness and population at the county level, but negatively related to the concentration of poverty. Our analysis reveals a two-tier system of public interest representation in which national organizations engage in a variety of social change strategies, whereas local and regional organizations utilize more limited strategies and depend more on governmental funding. These patterns have implications for access to justice in the United States today.
“We Don't Believe in Transitional Justice:” Peace and the Politics of Legal Ideas in Colombia
Authors: Jamie Rebecca Rowen
Published: November 2016

This article draws on law and society theories on the circulation of legal ideas to explain the instrumentalization of transitional justice in Colombia. Most scholarship explains transitional justice as a theoretical framework or as a set of instruments that helps redress mass violence. In contrast, this study reveals that the idea serves as a placeholder for different political actors to promote their respective interests. Drawing on over fifty interviews, the study suggests that the power of transitional justice lies in its malleability, which is both its strength and its weakness, as those with different political agendas can appropriate the idea in contradictory ways. The findings emphasize that understanding transitional justice requires a turn from abstract analyses that either take the idea for granted or try to define its meaning toward examining how people on the ground understand the idea, and how they translate those understandings into political action.
The Challenges of Extreme Moral Stress: Claudia Card's Contributions to the Formation of Nonideal Ethical Theory
Authors: Norlock Kathryn J.
Published: November 2016

This essay argues that Claudia Card numbers among important contributors to nonideal ethical theory (NET), and it advocates for the worth of NET. Following philosophers including Lisa Tessman and Charles Mills, the essay contends that it is important for ethical theory, and for feminist purposes, to carry forward the interrelationship that Mills identifies between nonideal theory and feminist ethics. Card's ethical theorizing assists in understanding that interrelationship. Card's philosophical work includes basic elements of NET indicated by Tessman, Mills, and others, and further offers two important and neglected elements to other nonideal ethical theorists: (i) her rejection of the “administrative point of view,” and (ii) her focus on “intolerable harms” as forms of “extreme moral stress” and obstacles to excellent ethical lives. The essay concludes that Card's insights are helpful to philosophers in developing nonideal ethical theory as a distinctive contribution to, and as a subset of, nonideal theory.
Business travellers' connections to home: ICTs supporting work‐life balance
Authors: Ladkin Adele , Willis Cheryl , Jain Juliet , Clayton William , Marouda Marina
Published: November 2016

This paper examines the role of information communication technology in enabling connections to home for work‐related travellers. Although digital connectivity for work‐related tasks are well researched, the use of digital technology for home communication is under‐researched. The study draws on a qualitative study of UK‐based organisations and business travellers to explore how these travellers use ICTs for personal use while ‘on the move’. The findings reveal that organisations are supportive of work‐life balance for employees, but fail to consider specific needs of those whose work takes them away from home. For business travellers, insights are gained into practices around connecting to home and the value of this virtual presence for relationships with family while absent and work‐life balance. The study identifies and discusses practice occurring around three activities; checking in, maintaining relationships with home and sharing experiences.
Life history and eco‐evolutionary dynamics in light of the gut microbiota
Authors: Macke Emilie , Tasiemski Aurélie , Massol François , Callens Martijn , Decaestecker Ellen
Published: November 2016

The recent emergence of powerful genomic tools, such as high‐throughput genomics, transcriptomics and metabolomics, combined with the study of gnotobiotic animals, have revealed overwhelming impacts of gut microbiota on the host phenotype. In addition to provide their host with metabolic functions that are not encoded in its own genome, evidence is accumulating that gut symbionts affect host traits previously thought to be solely under host genetic control, such as development and behavior. Metagenomics and metatranscriptomics studies further revealed that gut microbial communities can rapidly respond to changes in host diet or environmental conditions through changes in their structural and functional profiles, thus representing an important source of metabolic flexibility and phenotypic plasticity for the host. Hence, gut microbes appear to be an important factor affecting host ecology and evolution which is, however, not accounted for in life‐history theory, or in classic population genetics, ecological and eco‐evolutionary models. In this forum, we shed new light on life history and eco‐evolutionary dynamics by viewing these processes through the lens of host– microbiota interactions. We follow a three‐level approach. First, current knowledge on the role of gut microbiota in host physiology and behavior points out that gut symbionts can be a crucial medium of life‐history strategies. Second, the particularity of the microbiota is based on its multilayered structure, composed of both a core microbiota, under host genetic and immune control, and a flexible pool of microbes modulated by the environment, which differ in constraints on their maintenance and in their contribution to host adaptation. Finally, gut symbionts can drive the ecological and evolutionary dynamics of their host through effects on individual, population, community and ecosystem levels. In conclusion, we highlight some future perspectives for integrative studies to test hypotheses on life history and eco‐evolutionary dynamics in light of the gut microbiota.
Current evidence for the use of sugammadex in children
Authors: Tobias Joseph D.
Published: November 2016

Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade with a mechanism that differs from the commonly used, acetylcholinesterase inhibitors. Although sugammadex has not received approval from the United States Food & Drug administration in children, its use has already been reported to reverse neuromuscular blockade in several clinical scenarios in the pediatric population including the ‘cannot intubate–cannot ventilate’ scenario. To date, there remains limited data from prospective trials in the pediatric‐aged patient. Anecdotal use has been reported for the reversal of neuromuscular blockade in difficult clinical scenarios such as children with neuromuscular diseases including myasthenia gravis, Duchenne muscular dystrophy, and myotonic dystrophy.
Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update
Authors: Dissen GA , Adachi K , Lomniczi A , Chatkupt T , Davidson BL , Nakai H , Ojeda SR
Published: November 2016

Contents

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus‐based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non‐pathogenic adeno‐associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild‐type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non‐hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off‐target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.
Spatial Ca2+ profiling: decrypting the universal cytosolic Ca2+ oscillation
Authors: Samanta Krishna , Parekh Anant B.
Published: November 2016

Stimulation of cell‐surface receptors that couple to phospholipase C to generate the second messenger inositol trisphosphate often evokes repetitive oscillations in cytosolic Ca2+. Signalling information is encoded in both the amplitude and frequency of the Ca2+ spikes. Recent studies have revealed that the spatial profile of the oscillation also imparts signalling power; Ca2+ microdomains near store‐operated CRAC channels in the plasma membrane and inositol trisphosphate‐gated channels in the endoplasmic reticulum both signal to distinct downstream targets. Spatial profiling therefore increases the transduction power of the universal oscillatory cytosolic Ca2+ signal.

image
High resolution three‐dimensional reconstruction of fibrotic skeletal muscle extracellular matrix
Authors: Gillies Allison R. , Chapman Mark A. , Bushong Eric A. , Deerinck Thomas J. , Ellisman Mark H. , Lieber Richard L.
Published: November 2016

Key points

Fibrosis occurs secondary to many skeletal muscle diseases and injuries, and can alter muscle function.

It is unknown how collagen, the most abundant extracellular structural protein, alters its organization during fibrosis.

Quantitative and qualitative high‐magnification electron microscopy shows that collagen is organized into perimysial cables which increase in number in a model of fibrosis, and cables have unique interactions with collagen‐producing cells.

Fibrotic muscles are stiffer and have a higher concentration of collagen‐producing cells.

These results improve our understanding of the organization of fibrotic skeletal muscle extracellular matrix and identify novel structures that might be targeted by antifibrotic therapy.

Skeletal muscle extracellular matrix (ECM) structure and organization are not well understood, yet the ECM plays an important role in normal tissue homeostasis and disease processes. Fibrosis is common to many muscle diseases and is typically quantified based on an increase in ECM collagen. Through the use of multiple imaging modalities and quantitative stereology, we describe the structure and composition of wild‐type and fibrotic ECM, we show that collagen in the ECM is organized into large bundles of fibrils, or collagen cables, and the number of these cables (but not their size) increases in desmin knockout muscle (a fibrosis model). The increase in cable number is accompanied by increased muscle stiffness and an increase in the number of collagen producing cells. Unique interactions between ECM cells and collagen cables were also observed and reconstructed by serial block face scanning electron microscopy. These results demonstrate that the muscle ECM is more highly organized than previously reported. Therapeutic strategies for skeletal muscle fibrosis should consider the organization of the ECM to target the structures and cells contributing to fibrotic muscle function.
Mixture of ZEP and PMMA with varying ratios for tunable sensitivity as a lift-off resist with controllable undercut
Authors: Zheng Shuo , Dey Ripon Kumar , Aydinoglu Ferhat , Cui Bo
Published: November 2016

A lift-off process is a popular method to pattern metals, especially for the noble metals that are hard to dry-etch. For a “clean” lift-off process, an undercut profile is critical and is commonly achieved by using a bilayer resist stack. A resist with tunable sensitivity is apparently the most desirable, since it offers a controlled amount of undercut when used as the bottom layer, with the top layer being a less sensitive resist. In this study, the authors show that a simple mixture of poly (methyl methacrylate) (PMMA) and ZEP can offer tunable sensitivity by adjusting the ratio of the two resists dissolved in anisole. Higher sensitivity was attained by increasing the ZEP content in the mixture since ZEP is about 3× more sensitive than PMMA. However, the relationship is not a linear one, and the contrast curve for a mixture containing more PMMA (e.g., PMMA:ZEP ratio of 2:1) is closer to that of pure ZEP than to PMMA. For dense line array patterns with a periodicity of 200 and 500 nm, a moderate undercut obtained by using a low ZEP concentration (PMMA:ZEP = 2:1 as the bottom layer, PMMA as the top layer) gave the result for lift-off of 100 nm Cr. While using pure ZEP as the bottom layer, the undercut was often too large that the resist lines collapsed because of capillary force or even completely detached when the adjacent undercut merged together.
Acoustically diverse vocalization repertoire in the Himalayan leaf-nosed bat, a widely distributed Hipposideros species
Authors: Lin Aiqing , Jiang Tinglei , Feng Jiang , Kanwal Jagmeet S.
Published: November 2016

Insectivorous bats vocalize to both communicate with conspecifics and to echolocate. The communicative vocalizations or “calls” of bats either consist of or are constructed from discrete acoustic units, termed “syllables.” This study examined syllable diversity in the Himalayan leaf-nosed bat, Hipposideros armiger, a species that is widely distributed across Southeast Asia. This social species' vocalizations were hypothesized to consist of a wide variety of syllables facilitating its social interactions. To test this hypothesis, multiple acoustic parameters were measured from recorded vocalizations to map the acoustic boundaries of syllables. Spectrographic signatures were used to classify all recorded sounds into 35 distinct syllable types—18 as simple syllables and 17 as composites. K-means clustering independently provided an optimal fit of simple syllables into 18 clusters with a good correspondence to 15 spectrographically assigned syllable types. Discriminant analysis further confirmed the spectrographic classification of constant frequency syllables (0% misclassification) and revealed a low (<15%) misclassification of spectrograms for all examples of frequency modulation syllables. Multidimensional scaling of mean values of multiple parameters provided a spectrographically constrained relational mapping of syllable types within two dimensions. These data suggest that H. armiger has a complex, well organized syllabic repertoire despite simple syllables being rarely emitted in isolation.
Perception of music dynamics in concert hall acoustics
Authors: Pätynen Jukka , Lokki Tapio
Published: November 2016

Dynamics is one of the principal means of expressivity in Western classical music. Still, preceding research on room acoustics has mostly neglected the contribution of music dynamics to the acoustic perception. This study investigates how the different concert hall acoustics influence the perception of varying music dynamics. An anechoic orchestra signal, containing a step in music dynamics, was rendered in the measured acoustics of six concert halls at three seats in each. Spatial sound was reproduced through a loudspeaker array. By paired comparison, naive subjects selected the stimuli that they considered to change more during the music. Furthermore, the subjects described their foremost perceptual criteria for each selection. The most distinct perceptual factors differentiating the rendering of music dynamics between halls include the dynamic range, and varying width of sound and reverberance. The results confirm the hypothesis that the concert halls render the performed music dynamics differently, and with various perceptual aspects. The analysis against objective room acoustic parameters suggests that the perceived dynamic contrasts are pronounced by acoustics that provide stronger sound and more binaural incoherence by a lateral sound field. Concert halls that enhance the dynamics have been found earlier to elicit high subjective preference.
Innovation and Entrepreneurship in Kinesiology: Survey Results from the 2016 AKA Workshop
Authors: Carter Jason R. , McCullagh Penny , Kreider Rick
Published: November 2016

Over the past decade, institutions of higher education have been forced to become more innovative and entrepreneurial, seeking creative solutions to budget challenges. This has been particularly important within kinesiology programs, which represent one of the largest growing sectors of higher education over the past 10–15 years. In preparation for the 2016 American Kinesiology Association (AKA) Leadership Workshop, a survey was administered by the AKA to capture key institutional classifications (i.e., Carnegie classification, institutional size, public vs. private designation) and department chair or designated administrator perceptions on entrepreneurial issues relevant to their unit. Sixty-eight of 881 units surveyed responded, yielding a response rate of 7.7%. The majority of respondents (67%) indicated a unit funding model that was based on the previous year’s level (i.e., historical budget model). While the majority of respondents reported that their unit is provided with “adequate to plentiful” resources (59%), this varied widely based on institutional classification. Specifically, baccalaureate institutions (Chi-square 18.054, p < .001) and institutions with < 5,000 students (Chi-square 10.433, p & .015) had the least favorable perceptions of unit resource allocation. For the majority of entrepreneurial activities and partnerships (5 of 8 targeted questions), ≥ 50% of the respondents reported “no involvement.” There was a significant mismatch between actual vs. expected time spent by the department chair on fundraising activities (Chi-square 4.627, p = .031), with higher expectations than actual time spent on fundraising. In summary, the AKA survey suggests that there is tremendous heterogeneity in perceptions of and participation in entrepreneurial activities within kinesiology, and that there remains strategic areas of opportunity within the field.
Entrepreneurial Ideas for Kinesiology Departments: A Process-Based Approach
Authors: Bellar David , Gilson Todd A. , Hannon James C.
Published: November 2016

Higher education is in a period of flux. For many public institutions, state support has decreased over the past decade, resulting in the notion of doing more with less. Using an inverted triangle approach, this article examines how both institutions and departments are coping with their present reality using innovative and entrepreneurial ideas. First, the story of how public institutions in the state of Illinois are responding to decreased state appropriations and declining K–12 enrollments is discussed. Second, a rich example of how one institution completed the strategic planning process—from conceptualization to implementation—is shared. Finally, one department’s multifaceted plan to handle declining state support is shared.
Building Department Visibility and Support through Strategic Partnerships and Innovation
Authors: Carter Jason R. , Williams Nancy I. , Chodzko-Zajko Wojtek J.
Published: November 2016

Building departmental visibility and support is essential to the success of any kinesiology unit. This paper provides an overview of different strategies taken by three American Kinesiology Association member departments to advance their respective units. Each program was faced with unique institutional goals and structures, yet each institutional example highlights the shared theme of building strategic partnerships and cultivating a culture of entrepreneurship and innovation. Common strategies across the three institutions included a genuine understanding of university priorities and politics, chair and faculty leadership, strong internal and external communication, a willingness to lead and think creatively, and maintaining a focus on academic and educational excellence.
Building External Support, Increasing Visibility, and Enhancing Development Activity in Kinesiology
Authors: Thomas Jerry R. , Andrew Damon , Moran Patricia A. , Miller Wayne , Lee Amelia M.
Published: November 2016

In today’s challenging economic climate at most universities, kinesiology administrators are becoming increasingly aware of the need to participate in activities that will generate alternative revenue sources related to their academic mission. The ways deans and development officers communicate with alumni, potential donors, upper administrative leaders, and legislatures will all impact how successful the efforts to develop funds and partnerships will be. Successful fundraisers are those who can generate strategic alliances, create and market a plan that relates needs to societal issues of public interest and university priorities, and are able to identify partnerships that will produce an increase in resources. This paper provides strategies for identifying and connecting with key donors, building partnerships, developing the plan and cultivating internal and external audiences, aligning needs with university priorities, and working with legislatures.
Securing External Funding: Five Strategies for Administrators and Faculty
Authors: Thomas Katherine Thomas
Published: November 2016

External funding increases as the number of quality proposals submitted increases; increasing the number of faculty submitting proposals is a logical step to increase external funding. Reflecting on a physical educator’s > $1.5 million grant portfolio, two main themes emerge: the role of the PI and the unit administrator. Realizing increases in external funding is in part a result of administrators empowering faculty for success, and five administrator strategies have been identified. These strategies include: (1) value all sources of external funding (e.g., teaching, research, outreach, federal, foundation), (2) reward the process and the outcomes (a good proposal is equal to a data-based paper), (3) facilitate connections for collaboration (e.g., spread the word about your faculty), (4) provide infrastructure (from labs to personnel evaluation), (5) identify and develop potential. Important strategies for PIs include: (1) write proposals, (2) take risks, (3) answer the phone, (4) details matter, and (5) seek collaborators.
A new evolutionary classic
Authors: Pennisi Elizabeth
Published: November 2016

At least a dozen times, rove beetles independently evolved the ability to invade and steal from army ant nests.
A general catalytic β-C–H carbonylation of aliphatic amines to β-lactams
Authors: Willcox Darren , Chappell Ben G. N. , Hogg Kirsten F. , Calleja Jonas , Smalley Adam P. , Gaunt Matthew J.
Published: November 2016

CO takes the lead to make β-lactam rings

Strained β-lactam rings are a key feature of penicillin and some other drugs. Willcox
et al.
designed a versatile route to these four-membered ring motifs through the palladiumcatalyzed coupling of carbon monoxide with secondary amines. The bulky carboxylate ligand appears to facilitate preliminary CO incorporation into a Pd anhydride, which is then attacked by the amine to set up ring closure via C–H activation. This approach broadens the substrate scope compared with a previous scheme in which C–H activation preceded CO insertion.

Science
, this issue p.
851
The DNA methyltransferase DNMT3C protects male germ cells from transposon activity
Authors: Barau Joan , Teissandier Aurélie , Zamudio Natasha , Roy Stéphanie , Nalesso Valérie , Hérault Yann , Guillou Florian , Bourc’his Déborah
Published: November 2016

Combating parasitic DNA by methylation

DNA methylation plays an important role in repressing the expression of “parasitic” DNAs, such as transposable elements, which have invaded our genomes. Mammals have three DNA methyltransferase enzymes. Barau
et al.
discovered a fourth DNA methyltransferase enzyme in mice. The enzyme DNMT3C is a duplication of DNMT3B and is found in male germ cells. There it targets evolutionarily young transposons, of which there is a heavy burden in the mouse genome. DNMT3C methylates and silences the young transposons, preserving male fertility.

Science
, this issue p.
909
Toward a national, sustained U.S. ecosystem assessment
Authors: Jackson Stephen T. , Duke Clifford S. , Hampton Stephanie E. , Jacobs Katharine L. , Joppa Lucas N. , Kassam Karim-Aly S. , Mooney Harold A. , Ogden Laura A. , Ruckelshaus Mary , Shogren Jason F.
Published: November 2016

Pieces are in place, but need coordination and policy focus
Command of active matter by topological defects and patterns
Authors: Peng Chenhui , Turiv Taras , Guo Yubing , Wei Qi-Huo , Lavrentovich Oleg D.
Published: November 2016

Directing traffic with patterns

Biological entities, such as bacteria, may direct their motion in response to their environment, but this usually does not lead to large-scale patterns or collective behavior. Peng
et al.
found that the orientational ordering of a liquid crystal could direct the flow of self-propelling bacteria, which in turn influenced the patterning of the liquid crystal molecules. Patterns on a substrate caused surface anchoring of the liquid crystals that transmitted to the ordering of the bacteria, thus imparting control on what would otherwise be chaotic out-of-equilibrium behavior.

Science
, this issue p.
882
Revealing the dynamics of a large impact
Authors: Barton Penny
Published: November 2016

Drilling into the Chicxulub crater provides constraints on how it formed
Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals
Authors: Bellinger Andrew M. , Jafari Mousa , Grant Tyler M. , Zhang Shiyi , Slater Hannah C. , Wenger Edward A. , Mo Stacy , Lee Young-Ah Lucy , Mazdiyasni Hormoz , Kogan Lawrence , Barman Ross , Cleveland Cody , Booth Lucas , Bensel Taylor , Minahan Daniel , Hurowitz Haley M. , Tai Tammy , Daily Johanna , Nikolic Boris , Wood Lowell , Eckhoff Philip A. , Langer Robert , Traverso Giovanni
Published: November 2016

A newly developed platform capable of oral, ultra–long-acting drug delivery could be applied against the malaria vector in elimination programs.
Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity
Authors: Minakuchi M. , Sugiyama K. , Kato Y. , Naito T. , Okuwaki M. , Kawaguchi A. , Nagata K.
Published: November 2016

The genome of influenza virus (viral RNA [vRNA]) is associated with the nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using a
Saccharomyces cerevisiae
replicon system and a single-gene deletion library of
Saccharomyces cerevisiae
(T. Naito, Y. Kiyasu, K. Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci USA, 104:18235–18240, 2007,
https://doi.org/10.1073/pnas.0705856104
). In infected Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was reduced. Prp18 was found to stimulate
in vitro
viral RNA synthesis through its interaction with NP. Analyses using
in vitro
RNA synthesis reactions revealed that Prp18 dissociates newly synthesized RNA from the template after the early elongation step to stimulate the elongation reaction. We found that Prp18 functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. Based on these results, it is suggested that Prp18 accelerates influenza virus RNA synthesis as an NP chaperone for the processive elongation reaction.

IMPORTANCE
Templates for viral RNA synthesis of negative-stranded RNA viruses are not naked RNA but rather RNA encapsidated by viral nucleocapsid proteins forming vRNP complexes. However, viral basic proteins tend to aggregate under physiological ionic strength without chaperones. We identified the pre-mRNA processing factor Prp18 as a stimulatory factor for influenza virus RNA synthesis. We found that one of the targets of Prp18 is NP. Prp18 facilitates the elongation reaction of viral polymerases by preventing the deleterious annealing of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP to stimulate the formation of NP-RNA complexes. Based on these results, we propose that Prp18 may be required to maintain the structural integrity of vRNP for processive template reading.
Sfr1, a Tetrahymena thermophila Sfi1 Repeat Protein, Modulates the Production of Cortical Row Basal Bodies
Authors: Heydeck Westley , Stemm-Wolf Alexander J. , Knop Janin , Poh Christina C. , Winey Mark
Published: November 2016

Basal bodies and centrioles are structurally similar and, when rendered dysfunctional as a result of improper assembly or maintenance, are associated with human diseases. Centrins are conserved and abundant components of both structures whose basal body and centriolar functions remain incompletely understood. Despite the extensive study of centrins in
Tetrahymena thermophila
, little is known about how centrin-binding proteins contribute to centrin’s roles in basal body assembly, stability, and orientation. The sole previous study of the large centrin-binding protein family in
Tetrahymena
revealed a role for Sfr13 in the stabilization and separation of basal bodies. In this study, we found that Sfr1 localizes to all
Tetrahymena
basal bodies and complete genetic deletion of
SFR1
leads to overproduction of basal bodies. The uncovered inhibitory role of Sfr1 in basal body production suggests that centrin-binding proteins, as well as centrins, may influence basal body number both positively and negatively.
Association between OCT-based microangiography perfusion indices and diabetic retinopathy severity
Authors: Lin Alexander D , Lee Aaron Y , Zhang Qinqin , Rezaei Kasra A , Kinyoun James , Wang Ruikang K , Lee Cecilia S
Published: November 2016

Aim

To evaluate the association between retinal capillary non-perfusion and diabetic retinopathy (DR) severity using optical coherence tomography-based microangiography (OMAG).

Methods

33 patients (51 eyes) with a history of diabetes underwent imaging with a 68 kHz Cirrus-5000 spectral domain OMAG prototype. Demographic and clinical characteristics were collected. The perfusion index (PI) was defined as per cent coverage of area by retinal vessels with flow, measured within a minimum of 6.8×6.8 mm2OMAG scan. The PI in each ETDRS zone was analysed using an automated algorithm. Univariate and multivariate analyses were used to determine the degree of association between PI and DR severity.

Results

51 eyes with different DR severities were imaged. More severe DR was significantly associated with lower PI after adjusting for logarithm of the minimum angle of resolution best-corrected visual acuity, hyperlipidaemia, diabetes type and ETDRS ring in a multivariate mixed linear model. Compared with the none–mild non-proliferative diabetic retinopathy (NPDR) group, the moderate–severe NPDR group had 2.7 lower PI (p=0.03) and proliferative DR group had 4.3 lower PI (p=0.003). All ETDRS zones except for the foveal centre showed inverse associations between PI and DR severity (p values<0.001 to 0.862).

Conclusions

A statistically significant inverse association exists between PI and DR severity. Our study suggests that PI may become a useful biomarker in evaluating and following the progression of DR.
Efficacy of two injection-site localisation techniques for botulinum toxin injections: a single-blind, crossover, randomised trial protocol among adults with hemiplegia due to stroke
Authors: Morel Claire , Hauret Isabelle , Andant Nicolas , Bonnin Armand , Pereira Bruno , Coudeyre Emmanuel
Published: November 2016

Introduction

Botulinum toxin injections are an effective treatment for limb spasticity following stroke. Different tracking techniques are used for this purpose: palpation, electrostimulation, electromyography and ultrasound. Yet very few studies have compared these different techniques, and none has successfully proved the superior efficacy of ultrasound-guided injections compared to another tracking method. The primary objective of our study was therefore to compare the efficacy of botulinum toxin injections depending on the tracking technique used: ultrasound versus electrostimulation.

Methods and analysis

This is a clinical, single-centre, prospective, interventional, single-blind, crossover, randomised trial. In total, 30 patients aged between 18 and 80 years presenting with triceps surae spasticity (evaluated >1 on the modified Ashworth scale) associated with hemiplegia sequelae due to stroke will be included. The patients will be selected among those who attend for consultation the Physical Medicine and Rehabilitation Department of the Clermont-Ferrand University Hospital. One group will receive the abobotulinumtoxinA (BoNT-A) injection guided by electrostimulation then ultrasound, and the second group's botulinum toxin injections will be guided by ultrasound then electrostimulation. For each patient, the duration of study participation is 5 months. The primary end point is variation in passive ankle dorsiflexion range of motion at slow and high speeds (Tardieu scale) with the knee straight.

Ethics and dissemination

This study received ethics approval form the CPP of Rhônes-Alpes region. Results will be published in a peer-reviewed journal.

Trial registration number

NCT01935544; pre-results.
Age and gender differential relationship between employment status and body mass index among middle-aged and elderly adults: a cross-sectional study
Authors: Noh Jin-Won , Kim Jinseok , Park Jumin , Oh In-Hwan , Kwon Young Dae
Published: November 2016

Objective

To determine the influence of age and gender, respectively, on the association between employment status and body mass index (BMI) in Korean adults using a large, nationally representative sample.

Design

Cross-sectional study.

Setting

South Korea.

Participants

7228 from fourth wave of the Korean Longitudinal Study of Aging (KLoSA), the survey's short form and year: ‘KLoSA 2012’.

Main outcome measures

BMI.

Results

BMI among the employed was higher than among the unemployed for those under 60. In terms of gender, employed men reported higher BMI than their unemployed counterparts, whereas employed women reported lower BMI than did unemployed women.

Conclusions

Employment status showed varying impacts on obesity by age and gender. Both unemployment at or after 60, as well as unemployment among women, is associated with increased BMI compared with unemployment among younger individuals or men, respectively.
Effects of increased positive end-expiratory pressure on intracranial pressure in acute respiratory distress syndrome: a protocol of a prospective physiological study
Authors: Chen Han , Xu Ming , Yang Yan-Lin , Chen Kai , Xu Jing-Qing , Zhang Ying-Rui , Yu Rong-Guo , Zhou Jian-Xin
Published: November 2016

Introduction

There are concerns that the use of positive end-expiratory pressure (PEEP) in patients with brain injury may potentially elevate intracranial pressure (ICP). However, the transmission of PEEP into the thoracic cavity depends on the properties of the lungs and the chest wall. When chest wall elastance is high, PEEP can significantly increase pleural pressure. In the present study, we investigate the different effects of PEEP on the pleural pressure and ICP in different respiratory mechanics.

Methods and analysis

This study is a prospective, single-centre, physiological study in patients with severe brain injury. Patients with acute respiratory distress syndrome with ventricular drainage will be enrolled. An oesophageal balloon catheter will be inserted to measure oesophageal pressure. Patients will be sedated and paralysed; airway pressure and oesophageal pressure will be measured during end-inspiratory occlusion and end-expiratory occlusion. Elastance of the chest wall, the lungs and the respiratory system will be calculated at PEEP levels of 5, 10 and 15 cm H2O. We will classify each patient based on the maximal ΔICP/ΔPEEP being above or below the median for the study population. 2 groups will thus be compared.

Ethics and dissemination

The study protocol and consent forms were approved by the Institutional Review Board of Fujian Provincial Hospital. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT02670733; pre-results.
Adjusted indices of multiple deprivation to enable comparisons within and between constituent countries of the UK including an illustration using mortality rates
Authors: Abel Gary A , Barclay Matthew E , Payne Rupert A
Published: November 2016

Objectives

Social determinants can have a major impact on health and as a consequence substantial inequalities are seen between and within countries. The study of inequalities between countries relies on having accurate and consistent measures of deprivation across the country borders. However, in the UK most socioeconomic deprivation measures are not comparable between countries. We give a method of adjusting the Indices of Multiple Deprivation (IMD) for use across the UK, describe the deprivation of each UK country, and show the problems introduced by naïvely using country-specific deprivation measures in a UK-wide analysis of mortality rates.

Setting/participants

42 148 geographic areas covering the population of the UK.

Outcome measures

Adjusted IMD scores based on the income and employment domains of country-specific IMD scores, adjusting for the contribution of other domains. The mortality rate among people aged under 75 years standardised to the UK age structure was compared between country-specific and UK-adjusted IMD quintiles.

Results

Of the constituent countries of the UK, Northern Ireland was the most deprived with 37% of the population living in areas in the most deprived fifth of the UK, followed by Wales with 22% of the population living in the most deprived fifth of the UK. England and Scotland had similar levels of deprivation. Deprivation-specific mortality rates were similar in England and Wales. Northern Ireland had lower mortality rates than England for each deprivation group, with similar differences for each group. Scotland had higher mortality rates than England for each deprivation group, with larger differences for more deprived groups.

Conclusions

Analyses of between-country and within-country inequalities by socioeconomic position should use consistent measures; failing to use consistent measures may give misleading results. The published adjusted IMD scores we describe allow consistent analysis across the UK.
Changing from continuous SC to transdermal clonidine to treat dystonia in a teenage boy with end-stage leucodystrophy
Authors: McCluggage Heather Louise
Published: November 2016

This case report discusses the problems encountered with dystonia in a teenage boy with end-stage calcifying leucodystrophy. It records the successful use of prolonged continuous subcutaneous clonidine and the change to thrice weekly transdermal clonidine.
Emergency procedures for patients with a continuous flow left ventricular assist device
Authors: Vierecke Juliane , Schweiger Martin , Feldman David , Potapov Evgenij , Kaufmann Friedrich , Germinario Lorenzo , Hetzer Roland , Falk Volkmar , Krabatsch Thomas
Published: November 2016

The number of ventricular assist devices (VADs) being implanted for terminal heart failure is rising at an exponential rate. These implanted patients have a decreased mortality, but still have significant morbidities, as the prevalence of these patients increases in the community. When VAD patients are discharged to home, they will very likely require emergency medical services (EMSs) and emergency medical doctors (EDs) with their future care. The interface of these patients with the community would suggest an increasing prevalence of encounters requiring the need for acute medical care. This will place the initial responsibility of these patients in the hands of EMS first responders and emergency room providers. To date, there is very little literature published on out-of-hospital or ED care for VAD patients. Most EMS personnel and ED feel uncomfortable treating a patient with a VAD because they have not had sufficient exposure. The cardiovascular treatment of VAD patients in the field can pose different challenges typically encountered including difficulties measuring a pulse and sometimes undetectable BP. Despite these unique challenges, official guidelines or even standard operating procedures regarding the emergency treatment of VAD patients are still lacking. We present a basic overview of the most commonly used left VAD systems and propose guidelines that should be followed in the event of an emergency with a VAD patient out of hospital.