bluuebunny/crossref_metadata_2025 huggingface dataset:
Weyl–Kondo semimetal in heavy-fermion systems
Authors: Lai Hsin-Hua , Grefe Sarah E. , Paschen Silke , Si Qimiao
Published: December 2017

Significance

While electronic states with nontrivial topology have traditionally been known in insulators, they have been evidenced in metals during the past 2 years. Such Weyl semimetals show topological protection while conducting electricity both in the bulk and on the surface. An outstanding question is whether topological protection can happen in metals with strong correlations. Here, we report theoretical work on a strongly correlated lattice model to demonstrate the emergence of a Weyl–Kondo semimetal. We identify Weyl fermions in the bulk and Fermi arcs on the surface, both of which are associated with the many-body phenomenon called the Kondo effect. We determine a key signature of this Weyl–Kondo semimetal, which is realized in a recently discovered heavy-fermion compound.
MicroRNA-351
promotes schistosomiasis-induced hepatic fibrosis by targeting the vitamin D receptor
Authors: He Xing , Sun Yue , Lei Nanhang , Fan Xiaobin , Zhang Cheng , Wang Yange , Zheng Kuiyang , Zhang Dongmei , Pan Weiqing
Published: December 2017

Significance

Hepatic fibrosis is the final common pathological outcome of many chronic liver diseases and occurs when hepatic stellate cells (HSCs) are activated to become fibrogenic myofibroblasts. To date, there are still no approved antifibrotic therapies. Accumulating evidence suggests that targeting the deregulated miRNAs could mitigate disease outcomes. In this study, using a well-studied model of human schistosomiasis, we show that elevated
miR-351
promotes the activation of HSCs after infection by targeting the vitamin D receptor, and inhibition of
miR-351
in the liver mediated by rAAV8 protects the host from lethal infection by alleviating hepatic fibrosis. This study provides insights into the mechanisms that result in schistosomiasis-related hepatic fibrosis and targets of intervention for schistosomiasis and other fibrotic diseases.
SIMS analyses of the oldest known assemblage of microfossils document their taxon-correlated carbon isotope compositions
Authors: Schopf J. William , Kitajima Kouki , Spicuzza Michael J. , Kudryavtsev Anatoliy B. , Valley John W.
Published: December 2017

Significance

Although the existence of the Archaea (one of three all-encompassing domains of life) in the Archean Eon (4,000 to 2,500 million years ago) has been inferred from carbon isotopes in bulk samples of ancient rocks, their cellular fossils have been unknown. We here present carbon isotope analyses of 11 microbial fossils from the ∼3,465-million-year-old Western Australian Apex chert from which we infer that two of the five species studied were primitive photosynthesizers, one was an Archaeal methane producer, and two others were methane consumers. This discovery of Archaea in the Archean is consistent with the rRNA “tree of life,” confirms the earlier disputed biogenicity of the Apex fossils, and suggests that methane-cycling methanogen−methanotroph communities were a significant component of Earth’s early biosphere.
Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets
Authors: Nam Inho , Nam Hong Gil , Zare Richard N.
Published: December 2017

Significance

Discovery of an improved prebiotic method for the synthesis of ribonucleosides provides support to theories that posit a central role for RNA in the origin of life. It has been assumed that ribonucleosides arose through an abiotic process in which ribose and nucleobases became conjoined, but the direct condensation of nucleobases with ribose to give ribonucleosides in bulk solution is thermodynamically uphill. We show a general synthetic path for ribonucleosides, both purine and pyrimidine bases, using an abiotic salvage pathway in a microdroplet environment with divalent magnesium ion (Mg
2+
) as a catalyst. Purine and pyrimidine ribonucleosides are formed simultaneously under the same conditions, which suggests a possible scenario for the spontaneous production of random ribonucleosides necessary to generate various types of primitive RNA.
Prologue to a restoration foretold: negotiating heritage in a former German village in Georgia
Authors: Voell Stéphane , Kamm Elke
Published: December 2017

Two hundred years ago, Germans emigrated to the South Caucasus. Settling in villages like Asureti (formerly Elisabethtal) in Georgia, they became quite wealthy. In 1941, the Germans were deported to Central Asia and Georgians were resettled in the empty villages. In Asureti there still exist numerous impressive, albeit poorly conserved half-timbered houses that are a witness to this history. Our story begins with plans to restore these buildings so as to attract tourists to Asureti and the uncertainty that these plans have called forth among the local population. Would todays village residents be reduced to mere bystanders in the development of their own villages, displaced by a polished image of successful German immigrants? Traditionally, heritage studies examine strategies linked to the concrete restoration of the built environment and how the local population responds. We look here at what happens before such restoration projects are realized. Long before the first craftsmen arrive, the people of Asureti have begun to chip away at the perfect image of the German giants so as to not disappear in their shadows. The actual restoration of the lived environment has yet to begin; how this lived environment might one day be understood is already underway.
Gluing together the pieces of crinophagy
Authors: Short Ben
Published: December 2017

Study identifies some of the molecules involved in targeting excess secretory vesicles to lysosomes for degradation.
Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects
Authors: Rujano Maria A. , Cannata Serio Magda , Panasyuk Ganna , Péanne Romain , Reunert Janine , Rymen Daisy , Hauser Virginie , Park Julien H. , Freisinger Peter , Souche Erika , Guida Maria Clara , Maier Esther M. , Wada Yoshinao , Jäger Stefanie , Krogan Nevan J. , Kretz Oliver , Nobre Susana , Garcia Paula , Quelhas Dulce , Bird Thomas D. , Raskind Wendy H. , Schwake Michael , Duvet Sandrine , Foulquier Francois , Matthijs Gert , Marquardt Thorsten , Simons Matias
Published: December 2017

The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.
Phosphorylation promotes activation-induced cytidine deaminase activity at the Myc oncogene
Authors: Mu Yunxiang , Zelazowska Monika A. , McBride Kevin M.
Published: December 2017

Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated. We determined that lithium, a clinically used therapeutic, induced high AID pS38 levels. Using lithium and an AID-S38 phospho mutant, we compared the role of pS38 in AID activity at the Ig switch region and off-target Myc gene. We found that deficient pS38 abated AID chromatin association and CSR but not mutation at Myc. Enhanced pS38 elevated Myc translocation and mutation frequency but not CSR or Ig switch region mutation. Thus, AID activity can be differentially targeted by phosphorylation to induce oncogenic lesions.
MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation
Authors: Singh Priti B. , Pua Heather H. , Happ Hannah C. , Schneider Christoph , von Moltke Jakob , Locksley Richard M. , Baumjohann Dirk , Ansel K. Mark
Published: December 2017

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92–deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses.
Creative Thinking Processes: Managing Innovative Efforts
Authors: Mumford Michael D. , Martin Robert , Elliott Samantha N.
Published: December 2017

Creative thinking is the basis for innovation in firms. And the need for strategy-relevant innovations has generated a new concern with how people go about solving the kinds of problems that call for creative thought. Although many variables influence people’s ability to provide creative problem solutions, it is assumed the ways in which people work with or process knowledge provides the basis for successful creative problem-solving efforts. Additionally, there has been evidence bearing on the processing activities that contribute to creative problem solving. It is noted that at least eight distinct processing activities are involved in most incidents of creative problem solving: (1) problem definition, (2) information gathering, (3) concept selection, (4) conceptual combination, (5) idea generation, (6) idea evaluation, (7) implementation planning, and (8) adaptive monitoring. There are strategies people employ in effective execution of each of these processes, along with contextual variables that contribute to, or inhibit, effective process execution. Subsequently, there are key variables that operate in the workplace that contribute to, or inhibit, effective execution of these processing operations. These observations, of course, lead to implications for management of innovative efforts in firms.
Preventing Bullying in School and Work Contexts
Authors: Coyne Iain , Campbell Marilyn
Published: December 2017

The knowledge base on bullying within school and working contexts has matured to the extent that researchers and practitioners are developing a deeper understanding of this complex social relationship problem. Although controversies still exist, evidence to date provides estimates of the prevalence of bullying, risk factors for bullying, antecedents of bullying, and theoretical models explaining bullying behavior and experience. There is little doubt that bullying in all its forms can have severe negative impacts on those involved in the bullying situation. As a result, it is important to establish coherent and evidence-based approaches to preventing bullying behavior in schools and workplaces.

In contrast, the development and evaluation of bullying interventions has not received the same level of support. Both in school and working contexts, there are examples of preventative approaches, but either these are espoused and not directly evaluated, or, where evaluations exist, data is limited in providing definitive answers to the success of an approach. An increasingly dominant voice advocates the creation of policies and laws for preventing workplace bullying. However, the usefulness of policies and laws on their own in reducing bullying is questionable—especially if they are developed with a quick-fix mentality. Trying to prevent such a complex social phenomenon requires an integrated program of actions necessitating significant investment over a prolonged period of time. Stakeholder engagement is paramount to any intervention. Ultimately, schools and workplaces need to try to develop a culture of dignity, fairness, respect, and conflict management which pervades the institution. Challenges remain on how to create such interventions, whether they are effective, and what impact societal values will have on the success of bullying prevention strategies.
The Creation of Pakistan
Authors: Jalal Ayesha
Published: December 2017

The All-India Muslim League first voiced the demand for a Muslim homeland based on India’s northwestern and northeastern provinces in March 1940. Seven years later at the moment of British decolonization in the subcontinent, Pakistan emerged on the map of the world, an anomaly in the international community of nations with its two wings separated by a thousand miles of Indian territory. Over a million people died in the violence that accompanied partition while another 14½ million moved both ways across frontiers demarcated along ostensibly religious lines for the first time in India’s six millennia history. Commonly attributed to the age-old religious divide between Hindus, Muslims, and Sikhs, the causes of Pakistan’s creation are better traced to the federal problems created in India under British colonial rule. Despite sharing a common identity based on religious affiliation, Indian Muslims were divided along regional, linguistic, class, sectarian, and ideological lines. More Muslims live in India and Bangladesh than in Pakistan today, highlighting the clear disjunction between religiously informed identities and territorial sovereignty.

Mohammad Ali Jinnah, the leader of the All-India Muslim League, tried resolving the problem by claiming in 1940 that Indian Muslims were not a minority but a nation, entitled to the principle of self-determination. He envisaged a “Pakistan” based on undivided Punjab and Bengal. Since this left Muslims in the Hindu-majority provinces out of the reckoning, Jinnah left it an open question whether “Pakistan” and Hindustan would form a confederation covering the whole of India or make treaty arrangements as two separate sovereign states. In the end Jinnah was unable to achieve his larger aims and had to settle for a Pakistan based on the Muslim-majority districts of Punjab and Bengal, something he had rejected out of hand in 1944 and then again in 1946.
Migration and Obesity
Authors: Cunningham Solveig A. , Vandenheede Hadewijch
Published: December 2017

There are over 230 million international migrants worldwide, and this number continues to grow. Migrants tend to have limited access to and knowledge about resources and preventative care in their communities of reception, but nonetheless they are often in better health by many measures compared with native-born people in their communities of reception and with the people they left behind at their place of origin. With time since arrival, however, immigrants’ health advantages often dissipate and they experience increases in health problems, especially obesity and diabetes, which are chronic diseases that are increasingly prevalent in the overall population as well and are associated with multiple co-morbidities and limitations. It may be that immigrants have specific health endowments leading to these health patterns, or that the processes involved in migration, including exposure to new environments, behavioral change, and stress of migration may also affect risks of obesity and other chronic conditions. Understanding the health patterns of migrants can be useful in identifying their specific health needs, as well as contributing to our understanding of how specific environments, changes in environments, and individual health endowments interplay to shape the long-term health of populations.
Community-Oriented Primary Health Care for Improving Maternal, Newborn, and Child Health
Authors: Khan Amira M. , Lassi Zohra S. , Bhutta Zulfiqar A.
Published: December 2017

Nearly 80% of the world’s population lives in low- and middle-income countries (LMICs) and these regions bear the greatest burden of maternal, neonatal, and child mortality, with most of the deaths occurring at home. Much of global maternal and child mortality is attributable to easily preventable and treatable conditions. However, the challenge lies in reaching the most vulnerable communities, especially the rural populations, making it imperative that maternal, newborn, and child health (MNCH) interventions focus on communities in tandem with facility-based strategies. There is widespread consensus that delivering effective primary health care (PHC) interventions through the continuum of care, starting from pregnancy to delivery and then to the newborn, infant, and the young child, is an integral component of health strategies in high-, middle- and low-income settings.

Despite gaps in research, several effective community-based PHC approaches have been proven to impact MNCH positively. Implementation of these strategies is needed at scale in LMICs and in partnership with all stakeholders including the public and private sector. Community-based PHC, operating on the principles of community engagement and community mobilization, is now more critical than ever. Further robust studies are needed to evaluate certain strategies of community-based PHC and their impact on maternal and child health outcomes, such as the use of mobile technology and social franchises. Recognition of community health workers (CHWs) as a formal cadre and the integration of community-based health services within PHC are vital in strengthening efforts to impact maternal, neonatal, and child health outcomes positively. However, despite the importance of community-based PHC for MNCH in LMICs, the existence of a strong health system and skilled workforce is central to achieving positive health outcomes in these regions.
Health Care Access for Migrants in Europe
Authors: O'Donnell Catherine A.
Published: December 2017

Migration is a reality of today’s world, with over one billion migrants worldwide. While many choose to move voluntarily, others are forced to migrate due to economic reasons or to flee war, conflict, or persecution. Such migrants often find themselves in precarious and marginalized situations—particularly asylum seekers, refugees, and undocumented or irregular migrants. While often viewed as a single group, the legal status and entitlements of these three groups are different. This has implications for their ability to access health care; in addition, rights and entitlements vary across the 28 countries of the European Union and across different parts of national health systems. The lack of entitlement to receive care, including primary and secondary care, is a significant barrier for many asylum seekers and refugees and an even greater barrier for undocumented migrants. Other barriers include different health profiles and awareness of chronic disease risk amongst migrants; awareness of the organization of health systems in host countries; and language and communication. The use of professional interpreters can help to overcome communication barriers, but entitlement to free interpreting services is highly variable. Host countries need to consider how to ensure their health systems are “migrant-friendly”: solutions include provision of professional interpreters; ensuring that health care staff are aware of migrants’ rights to access health care; and increasing knowledge of migrants in relation to the organization of the health care system in their host country and how to access care, for example through the use of patient navigators. However, perhaps one of the greatest facilitators for migrants will be a more favorable political situation, which stops demonizing people who are forced to migrate due to situations out of their control.
Transnational Actors
Authors: Thiel Markus , Maslanik Jeffrey
Published: December 2017

“Transnational” is a frequently mentioned key word in international relations today; it is used to denote in a simplifying manner an organization working beyond state boundaries and acting independently from traditional state authorities. The scholarly recognition of such actors occurred relatively late in the field and advanced with the acceleration of globalizing economic, political, cultural, and social processes. Despite the appearance of transnational actors as a topical and palpable concern for academics and practitioners alike, questions of conceptual vagueness and relational indeterminacy remain, and the continual proliferation of these entities lend urgency to the need for more scholarly attention to these agents.
Trust and International Organization
Authors: Stiles Kendall W.
Published: December 2017

Trust is the expectation that one’s interests be looked after despite the possibility of exploitation by the one being trusted (trustee). Trusting always involves some risk on the part of the one trusting (truster). The truster is vulnerable—either by choice or by circumstance. One can never be absolutely sure that one’s interests are important to the trustee or that their past performance can allow one to predict future behavior. The trustee retains their agency and even has an incentive for betrayal in the future. Much of the research on trust in international relations is aimed at explaining cooperation amid anarchy. In this context, cooperation begins with a leap of faith by actors who trust generally rather than specifically. Such “generalized trusters” do not require evidence that the trustee in question is even trustworthy with respect to a particular issue, because all actors are assumed to be worthy of trust across all topics (assuming they have the capacity to act). This can be considered “credulity,” and it primarily involves having trustful attitudes, affects, emotions, or motivational structures that are not focused on specific people, institutions, or groups. Furthermore, one cannot speak of trust without some reference to affect, particularly because one can never absolutely calculate the odds of betrayal.
Anarchy in International Relations
Authors: Lechner Silviya
Published: December 2017

The concept of anarchy is seen as the cardinal organizing category of the discipline of International Relations (IR), which differentiates it from cognate disciplines such as Political Science and Political Philosophy. It is important to distinguish between concepts of anarchy and theories where anarchy operates as a central premise. The concept of anarchy can mean (a) a lack of a common superior in an interaction domain; (b) chaos or disorder; or (c) a horizontal relation between nominally equal entities sovereign states. The first and the third senses of “anarchy” are central to IR as a field, and figure as premises within three broad families of IR theory: (a) realism and neorealism, (b) English School theory (international society approach), and (c) Kant’s republican peace. Despite normative and conceptual differences otherwise, all three bodies of theory are ultimately based on Hobbes’s argument for a “state of nature,” and on an understanding that the key actors in international relations are sovereign states. The major challengers to the discourse of international anarchy are theories of international politics that rely on the methodology of economics as well as cognate approaches that prioritize the “global” over the “international” such as theories of globalization, global hierarchy, and global governance.
International Hierarchy
Authors: Barder Alexander D.
Published: December 2017

Recently, international hierarchy has taken center stage in international relations (IR) theory. Hierarchy is typically understood as a feature of domestic institutional stratification; it defines a set of social arrangements that reflects relations of authority. Where anarchy had once dominated IR theory, there are now substantial debates about how to account for hierarchical international relations between nominally sovereign states, as well as a prevalent conflation between hierarchy and hegemony to discuss unequal material and social arrangements. Yet the focus on hierarchy is nothing new. Theories such as Power Transition Theory and Hegemonic Stability Theory had attempted to understand the international system as a consequence of significant material imbalances of power. Moreover, critical theoretical approaches relying on Marxian analysis tended to emphasize the diverse hierarchical forms of international relations in the political-economic realm. More recent literature on international hierarchy is derived from a rationalist ontology, which explains why it would be a legitimate policy choice for states to enter into asymmetric relations. This literature understands hierarchy in its formal-juridical dimensions. In addition, discussions of international hierarchy by critical and postcolonial theorists take different ontological and epistemological starting points, as hierarchy can be understood in broader terms as a way of constituting and demarcating identities, for example. In other words, hierarchy is as much a social concept as a juridical one. However, this raises crucial theoretical questions concerning the differences between hegemony and hierarchy.
Religious Fundamentalist Families in School Social Work
Authors: Yates Jennifer
Published: December 2017

This article describes issues related to culturally competent social work practice with religiously fundamentalist families in public school settings. It addresses the history of religious fundamentalist identities, the complexity inherent in such identities, and the nature of fundamentalism. A review of issues related to culturally competent practice in educational settings is offered. Recommendations informed by spiritually sensitive and strength-based approaches are discussed. Challenges to working effectively with religiously conservative and fundamentalist families in educational settings are also explored. Emphasis is placed upon the practitioner’s role in developing spirituality-sensitive therapeutic relationships by improving religious literacy, developing enhanced self-awareness, and approaching clients from a perspective of cultural humility and a lens of intersectionality.
Conflicts in the coastal zone: human impacts on commercially important fish species utilizing coastal habitat
Authors: Brown Elliot J , Vasconcelos Rita P , Wennhage Håkan , Bergström Ulf , Støttrup Josianne G , van de Wolfshaar Karen , Millisenda Giacomo , Colloca Francesco , Le Pape Olivier
Published: December 2017

Coastal ecosystems are ecologically, culturally, and economically important, and hence are under pressure from diverse human activities. We reviewed the literature for existing evidence of effects of human-induced habitat changes on exploited fish utilizing coastal habitats. We focused on fish species of the Northeast Atlantic for which fisheries advice is provided by International Council for the Exploration of the Sea (ICES) and which utilize coastal habitats for at least one life-history stage (LHS). We found that 92% of these species are impacted by human activity in at least one LHS while utilizing coastal habitat and 38% in multiple stages. Anthropogenic pressures most commonly shown to impact these fish species were toxicants and pollutants (75% of species). Eutrophication and anoxia, invasive species, and physical coastal development affected about half of the species (58, 54, and 42% of species, respectively), while indirect fishing impacts affected a minority (17% of species). Moreover, 71% of the ICES advice species that utilize coastal habitats face impacts from more than one pressure, implying cumulative effects. Given that three-fourths of the commercial landings come from fish species utilizing coastal habitats, there is an obvious need for a better understanding of the impacts that human activities cause in these habitats for the development of ecosystem-based fisheries management.
A snapshot of health information exchange across five nations: an investigation of frontline clinician experiences in emergency care
Authors: Klapman Seth , Sher Emily , Adler-Milstein Julia
Published: December 2017

Objective

Ensuring the ability to exchange patient information among disparate electronic health records systems is a top priority and a domain of substantial public investment across countries. However, we know little about the extent to which current capabilities meet the needs of frontline clinicians.

Materials and Methods

We conducted in-person, semistructured interviews with emergency care physicians and nurses in select hospitals in Canada, Denmark, Finland, Germany, and the USA. We characterized the state of health information exchange (HIE) by country and used thematic analysis to identify the perceived benefits of access to complete past medical history (PMH), the conditions under which PMH is sought, and the challenges to accessing and using HIE capabilities.

Results

HIE approaches, and the information electronically accessible to clinicians, differed by country. Benefits of access to PMH included safer care, reduced patient length of stay, and fewer lab and imaging orders. Conditions under which PMH was sought included moderate-acuity patients, patients with chronic conditions, and instances where accessing PMH was convenient. Challenges to HIE access and use included difficulty knowing where information is located, delay in receiving information, and difficulty finding information within documents.

Discussion

Even with different HIE approaches across countries, all clinicians reported shortcomings in their country’s approach. Notably, challenges were similar and shaped the conditions under which PMH was sought.

Conclusion

As countries continue to pursue broad-based HIE, they appear to be facing similar challenges in realizing HIE value and therefore have an opportunity to learn from one another.
Designing and evaluating an automated system for real-time medication administration error detection in a neonatal intensive care unit
Authors: Ni Yizhao , Lingren Todd , Hall Eric S , Leonard Matthew , Melton Kristin , Kirkendall Eric S
Published: December 2017

Background

Timely identification of medication administration errors (MAEs) promises great benefits for mitigating medication errors and associated harm. Despite previous efforts utilizing computerized methods to monitor medication errors, sustaining effective and accurate detection of MAEs remains challenging. In this study, we developed a real-time MAE detection system and evaluated its performance prior to system integration into institutional workflows.

Methods

Our prospective observational study included automated MAE detection of 10 high-risk medications and fluids for patients admitted to the neonatal intensive care unit at Cincinnati Children’s Hospital Medical Center during a 4-month period. The automated system extracted real-time medication use information from the institutional electronic health records and identified MAEs using logic-based rules and natural language processing techniques. The MAE summary was delivered via a real-time messaging platform to promote reduction of patient exposure to potential harm. System performance was validated using a physician-generated gold standard of MAE events, and results were compared with those of current practice (incident reporting and trigger tools).

Results

Physicians identified 116 MAEs from 10 104 medication administrations during the study period. Compared to current practice, the sensitivity with automated MAE detection was improved significantly from 4.3% to 85.3% (P = .009), with a positive predictive value of 78.0%. Furthermore, the system showed potential to reduce patient exposure to harm, from 256 min to 35 min (P < .001).

Conclusions

The automated system demonstrated improved capacity for identifying MAEs while guarding against alert fatigue. It also showed promise for reducing patient exposure to potential harm following MAE events.
International Cognition and Cancer Task Force Recommendations for Neuroimaging Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients
Authors: Deprez Sabine , Kesler Shelli R , Saykin Andrew J , Silverman Daniel H S , de Ruiter Michiel B , McDonald Brenna C
Published: December 2017

Cancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 the International Cognition and Cancer Task Force (ICCTF) published consensus recommendations for core neuropsychological tests for studies of cancer populations. Over the past decade, studies have used neuroimaging techniques, including structural and functional magnetic resonance imaging (fMRI) and positron emission tomography, to examine the underlying brain basis for cancer- and treatment-related cognitive declines. As yet, however, there have been no consensus recommendations to guide researchers new to this field or to promote the ability to combine data sets. We first discuss important methodological issues with regard to neuroimaging study design, scanner considerations, and sequence selection, focusing on concerns relevant to cancer populations. We propose a minimum recommended set of sequences, including a high-resolution T1-weighted volume and a resting state fMRI scan. Additional advanced imaging sequences are discussed for consideration when feasible, including task-based fMRI and diffusion tensor imaging. Important image data processing and analytic considerations are also reviewed. These recommendations are offered to facilitate increased use of neuroimaging in studies of cancer- and treatment-related cognitive dysfunction. They are not intended to discourage investigator-initiated efforts to develop cutting-edge techniques, which will be helpful in advancing the state of the knowledge. Use of common imaging protocols will facilitate multicenter and data-pooling initiatives, which are needed to address critical mechanistic research questions.
Profound hearing loss following surgery in pediatric patients with posterior fossa low-grade glioma
Authors: Ghazwani Yahya , Qaddoumi Ibrahim , Bass Johnnie K , Wu Shengjie , Chiang Jason , Boop Frederick , Gajjar Amar , Sadighi Zsila
Published: December 2017

Background

Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery.

Methods

We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology.

Results

Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02).

Conclusions

Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.
Molecular and Morphological Characterization of Colletotrichum Species in the Colletotrichum gloeosporioides Complex Associated with Persimmon Anthracnose in South Korea
Authors: Hassan Oliul , Jeon Jong Yeob , Chang Taehyun , Shin Jun Sung , Oh Nam Kwon , Lee Yong Se
Published: December 2017

Anthracnose is a major disease of persimmon in the pre- and postharvest phase. Several species of Colletotrichum (Colletotrichum gloeosporioides, C. acutatum, and C. horii) have been reported as causal agents of persimmon anthracnose in South Korea. In this study, a collection of 50 isolates associated with persimmon anthracnose were collected from Sangju (n = 25) and Cheongdo-gun (n = 25), South Korea. The morphological characteristics of all 50 Colletotrichum isolates were similar, and it was difficult to identify the isolates to the species level. A subsample of eight isolates was characterized phylogenetically to ascertain species. BLAST search and phylogenetic analysis of the internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and actin (ACT) genes revealed two species: C. horii as well as a previously unreported persimmon anthracnose causal agent C. siamense. C. siamense isolates were confirmed again by phylogenetic analysis of the ITS, ACT, GAPDH, calmodulin, and Apn2-Mat1-2 intergenic spacer partial mating type genes. Koch’s postulates for C. horii and C. siamense were fulfilled, confirming the pathogenicity of the two species in persimmon fruit. Morphological characteristics (colony morphology and size and shape of conidia and appressoria) from two representative isolates support results of the phylogenetic analysis and match those of previous descriptions of C. horii and C. siamense.
Identification of Subsets of Genetic Alterations in KRAS-mutant Lung Cancer using Association Rule Mining
Authors: Tayou Junior
Published: December 2017

Background

Lung cancer is the leading cause of all cancer death accounting for 1 out of 4 cancer-related death in both men and women. KRAS mutations occur in ~ 25% of patients with lung cancer, and the presence of these mutations is associated with poor prognosis. Efforts to directly target KRAS or associated downstream MAPK or the PI3K/AKT/mTOR pathways have seen little or no benefits. One probable reason for the lack of progress in targeting KRAS-mutant tumors is the co-occurrence of other cell survival pathways and mechanisms.

Method and results

To identify other potential cell survival pathways in subsets of KRAS-mutant tumors, I performed unsupervised machine learning on somatic mutations in metastatic lung cancer from 725 patient samples. I identified 67 other genes that were mutated in at least 10% of the samples with KRAS alterations. This gene list was enriched with genes involved in the MAPK, AKT and STAT3 pathways, cell-cell adhesion, DNA repair, chromatin remodeling, and the Wnt/beta-catenin pathway. I also identified 160 overlapping subsets of 3 or more genes that code for oncogenic or oncosuppressive proteins that were mutated in at least 10% of KRAS-mutant tumors.

Conclusions

In this study, I identified genes that are co-mutated in KRAS-mutant lung cancer. I also identify subpopulations of KRAS-mutant lung cancer based on the set of genes that were also altered in the tumor samples. The design of research models that captures these subsets of KRAS-mutant tumors would enhance our understanding of the disease and facilitate personalized treatment for lung cancer patients with KRAS alterations.
A cytoplasmic Argonaute protein promotes the inheritance of RNAi
Authors: Xu Fei , Feng Xuezhu , Chen Xiangyang , Weng Chenchun , Yan Qi , Xu Ting , Hong Minjie , Guang Shouhong
Published: December 2017

RNAi-elicited gene silencing is heritable and can persist for multiple generations after its initial induction in C. elegans. However, the mechanism by which parental-acquired trait-specific information from RNAi is inherited by the progenies is not fully understood. Here, we identified a cytoplasmic Argonaute protein, WAGO-4, necessary for the inheritance of RNAi. WAGO-4 exhibits asymmetrical translocation to the germline during early embryogenesis, accumulates at the perinuclear foci in the germline, and is required for the inheritance of exogenous RNAi targeting both germline- and soma-expressed genes. WAGO-4 binds to 22G-RNAs and their mRNA targets. Interestingly, WAGO-4-associated endogenous 22G-RNAs target the same cohort of germline genes as CSR-1 and contain untemplated addition of uracil at the 3’ ends. The poly(U) polymerase CDE-1 is required for the untemplated uridylation of 22G-RNAs and inheritance of RNAi. Therefore, we conclude that, in addition to the nuclear RNAi pathway, the cytoplasmic RNAi machinery also promotes RNAi inheritance.
Electron and photon diagnostics for plasma acceleration-based FELs
Authors: Labat Marie , El Ajjouri Moussa , Hubert Nicolas , Andre Thomas , Loulergue Alexandre , Couprie Marie-Emmanuelle
Published: December 2017

It is now well established that laser plasma acceleration (LPA) is an innovative and good candidate in the beam acceleration field. Relativistic beams are indeed produced up to several GeV but their quality remains to be demonstrated in the highly demanding case of free-electron lasers (FELs). Several experiments have already shown the feasibility of synchrotron radiation delivery based on LPA but free-electron lasing has still to be achieved. Since the quality of the LPA beam inside the undulator is the critical issue, any LPA-based FEL experiment requires a refined characterization of the beam properties along the transport line and of the photon beam at the undulator exit. This characterization relies on diagnostics which must be adapted to the LPA specificities. Here, the electron and photon diagnostics already used on LPAs and required for LPA-based FELs are reviewed, and the critical points are illustrated using recent experiments performed around the world.
Single-shot arrival timing diagnostics for a soft X-ray free-electron laser beamline at SACLA
Authors: Owada Shigeki , Nakajima Kyo , Togashi Tadashi , Kayatama Tetsuo , Yabashi Makina
Published: December 2017

Arrival timing diagnostics performed at a soft X-ray free-electron laser (FEL) beamline of SACLA are described. Intense soft X-ray FEL pulses with one-dimensional focusing efficiently induce transient changes of optical reflectivity on the surface of GaAs. The arrival timing between soft X-ray FEL and optical laser pulses was successfully measured as a spatial position of the reflectivity change. The temporal resolution evaluated from the imaging system reaches ∼10 fs. This method requires only a small portion of the incident pulse energy, which enables the simultaneous operation of the arrival timing diagnostics and experiments by introducing a wavefront-splitting scheme.
Effect of reflection and refraction on NEXAFS spectra measured in TEY mode
Authors: Filatova Elena , Sokolov Andrey
Published: December 2017

The evolution of near-edge X-ray absorption fine structure in the vicinity of the K-absorption edge of oxygen for HfO2 over a wide range of incidence angles is analyzed by simultaneous implementation of the total-electron-yield (TEY) method and X-ray reflection spectroscopy. It is established that the effect of refraction on the TEY spectrum is greater than that of reflection and extends into the angular region up to angles 2θc. Within angles that are less than the critical angle, both the reflection and refraction strongly distort the shape of the TEY spectrum. Limitations of the technique for the calculation of optical constants from the reflection spectra using the Kramers–Kronig relation in the limited energy region in the vicinity of thresholds are discussed in detail.
Timing methodologies and studies at the FERMI free-electron laser
Authors: Mincigrucci Riccardo , Bencivenga Filippo , Principi Emiliano , Capotondi Flavio , Foglia Laura , Naumenko Denys , Simoncig Alberto , Dal Zilio Simone , Gessini Alessandro , Kurdi Gabor , Mahne Nicola , Manfredda Michele , Matruglio Alessia , Nikolov Ivaylo , Pedersoli Emanuele , Raimondi Lorenzo , Sergo Rudi , Zangrando Marco , Masciovecchio Claudio
Published: December 2017

Time-resolved investigations have begun a new era of chemistry and physics, enabling the monitoring in real time of the dynamics of chemical reactions and matter. Induced transient optical absorption is a basic ultrafast electronic effect, originated by a partial depletion of the valence band, that can be triggered by exposing insulators and semiconductors to sub-picosecond extreme-ultraviolet pulses. Besides its scientific and fundamental implications, this process is very important as it is routinely applied in free-electron laser (FEL) facilities to achieve the temporal superposition between FEL and optical laser pulses with tens of femtoseconds accuracy. Here, a set of methodologies developed at the FERMI facility based on ultrafast effects in condensed materials and employed to effectively determine the FEL/laser cross correlation are presented.
Temperature-induced pseudopolymorphism of molecular salts from a pyridyl bis-urea macrocycle and naphthalene-1,5-disulfonic acid
Authors: Som Bozumeh , Shue Jessica R. , Smith Mark D. , Shimizu Linda S.
Published: December 2017

Molecular salts, often observed as cocrystals, play an important role in the fields of pharmaceutics and materials science, where salt formation is used to tune the properties of active pharmaceutical ingredients (APIs) and improve the stability of solid-state materials. Salt formation via a proton-transfer reaction typically alters hydrogen-bonding motifs and influences supramolecular assembly patterns. We report here the molecular salts formed by the pyridyl bis-urea macrocycle 3,5,13,15,21,22-hexaazatricyclo[15.3.1.17,11]docosa-1(21),7(22),8,10,17,19-hexaene-4,14-dione, (1), and naphthalene-1,5-disulfonic acid (H2NDS) as two salt cocrystal solvates, namely 4,14-dioxo-3,5,13,15,21,22-hexaazatricyclo[15.3.1.17,11]docosa-1(21),7(22),8,10,17,19-hexaene-21,22-diium naphthalene-1,5-disulfonate dimethyl sulfoxide disolvate, C16H20N6O2
2+·C10H6O6S2
2−·2C2H6OS, (2), and the corresponding monosolvate, C16H20N6O2
2+·C10H6O6S2
2−·C2H6OS, (3). This follows the ΔpK
a rule such that there is a proton transfer from H2NDS to (1), forming the reported molecular salts through hydrogen bonding. Prior to salt formation, (1) is relatively planar and assembles into columnar structures. The salt cocrystal solvates were obtained upon slow cooling of dimethyl sulfoxide–acetonitrile solutions of the molecular components from two temperatures (363 and 393 K). The proton transfer to (1) significantly alters the conformation of the macrocycle, changing the formerly planar macrocycle into a step-shaped conformation with trans–cis urea groups in (2) or into a bowl-shape conformation with trans–trans urea groups in (3).