bluuebunny/crossref_metadata_2025 huggingface dataset:
Megaprojects as Games of Innovation
Authors: Miller Roger , Lessard Donald , Sakhrani Vivek
Published: September 2017

Megaprojects are intricate solutions shaped over many years to fit specific contexts and market needs. This chapter focuses on megaprojects as games of innovation in which sponsors, experts, and potentially opposing stakeholders interact to shape opportunities into projects and to design and deliver these projects. Each project calls for multiple innovative choices over time in the face of foreseeable and emerging issues, in a design tradespace that reflects multiple dimensions of value. Keeping these trade-offs alive over the life of the project requires that sponsors and experts master the inherent complexity of megaprojects and develop architectures and processes that deliver with requisite complexity.
Innovation and Flexibility in Megaprojects
Authors: Gann David M. , Davies Andrew , Dodgson Mark
Published: September 2017

This chapter examines how organizations responsible for three UK megaprojects—Heathrow Terminal 5, London 2012 Olympics, and Crossrail—have made significant efforts to create a more innovative and flexible delivery model. This new approach recognizes that over the life of a megaproject, new and unexpected options for delivering it will emerge, including opportunities to take advantage of innovative new practices, processes, and efficiencies made possible by new technology. Drawing upon strategy literature and empirical research conducted between 2005 and 2015, five dynamic capabilities or strategic processes are identified associated with a new innovative and flexible project delivery model—search, adaptive problem solving, test and trial, strategic innovation, and balancing—to help managers address the risks and opportunities involved in megaproject management.
Cracking the Code of Megaproject Innovation
Authors: Holzmann Vered , Shenhar Aaron , Zhao Yao , Melamed Benjamin
Published: September 2017

Boeing Corporation launched its 787 Dreamliner development program in the early 2000s, anticipating quick benefits from a growing demand for next-generation, advanced, and highly efficient aircraft. Budgeted at US$20 billion and designed by a global network of more than 700 subcontractors around the world, the Dreamliner had all the characteristics of a megaproject. Boeing expected that a collection of strategic innovations would add substantial business benefits, but that dream led to years of painful delays, cost overruns, and service introduction problems. Boeing’s previous extensive experience in commercial aircraft building was insufficient to deal with new challenges of a highly innovative program, and the Dreamliner’s difficulties typify many modern megaprojects. With accelerated technological growth, increased complexity of systems, and intensified demand for shorter time cycles, the challenge of strategic innovation in megaprojects becomes a universal struggle. This chapter presents a retrospective analysis of Boeing’s experience and offers a collection of global lessons for future megaprojects and programs.
Beyond Managerial Dilemmas
Authors: Tracey Paul , Creed W. E. Douglas
Published: September 2017

This chapter makes the case that institutional and paradox theorists should consider problems stretching beyond managerial concerns and corporate performance to focus attention on the paradoxes that characterize the most deep-rooted and contentious social issues facing societies and economies, suggesting a switch from organizational to institutional paradoxes. To illustrate, two vignettes are described—one focused on the legacy of the University of Georgetown’s slave-trading past, the other on the identity challenges faced by working-class people attending Cambridge University. Drawing from these vignettes, three sets of theoretical insights are presented which are fundamental to institutional paradox: that institutional paradoxes may be rooted in a desire for legitimacy; that temporality is a dynamic at the core of institutional paradox; and that the metaphor of multiple interconnected fault lines better captures the complexity inherent in paradox at the institutional level than the metaphor of dualities.
Naturalization
Authors: Orgad Liav
Published: September 2017

The manner in which new citizens should be created is one of the most complex questions in political theory. The law of naturalization functions as a gatekeeper—it is designed to include the desirable people and exclude the undesirable ones. This chapter explores legal and theoretical aspects of naturalization. Part I addresses the ultimate goal of naturalization—what function does it serve?—by presenting three goals: contract, political test, and nation-building. Part II seeks to present three ways to assess the ethics of naturalization, drawing on conceptual and utilitarian grounds. Part III examines three trends in naturalization policy in the West—legalization, devaluation, and liberalization (followed by a restrictive turn). Naturalization has been internationalized in the direction of creating a right to citizenship; citizenship is becoming a “commodity” whose nature is increasingly influenced by economic considerations; and the process of liberalization in access to the status of citizenship is facing a cultural restrictive turn.
Supranational Citizenship
Authors: Strumia Francesca
Published: September 2017

Supranational citizenship, as a concept, sits somewhat uncomfortably between the regional experience of European citizenship and discourses on global or cosmopolitan citizenship.European citizenship is too narrow to exhaust the concept, and global or cosmopolitan citizenship is too broad to embrace it firmly. Hence the contours of supranational citizenship remain rather fuzzy. This chapter endeavors to dispel this fuzziness. It traces a conceptual definition of supranational citizenship focusing on the re-articulation of citizenship beyond national boundaries on the basis of a norm of mutual recognition of belonging. It then distils from the concrete experience of European citizenship further elements to reinforce this definition. Ultimately, the chapter relies on the reinforced definition to identify contemporary examples of supranational citizenship beyond the EU context - such as Mercosur citizenship or CARICOM citizenship - and to chart the theoretical prospects of the concept.
The Historiography of Islamic Law During the Mamluk Sultanate
Authors: Ingalls Matthew B.
Published: September 2017

This article examines the historiography of Islamic law during the reign of the Mamluks. It asks what is specifically “Mamluk” about Islamic law and legal scholarship during the Mamluk sultanate and whether it is fruitful to view legal scholarship and the application of law through the lens of this particular political dynasty. The article first considers the historiography of Mamluk legal institutions from the Mamluk executive to the judiciary and law enforcement before discussing Mamluk madrasas, or Islamic educational institutions. It also explores three larger intellectual trends that would shape the development of medieval Islamic law but which are not readily confined to the Mamluk period alone: the proliferation of commentary works, the institution of the ijaza (license; certification) and encyclopaedism in Mamluk literature. The article concludes by assessing the state of the field and raising some questions for future research.
On History in Southwest Archaeology
Authors: Fowles Severin , Mills Barbara
Published: September 2017

As an introduction to the Handbook, this chapter examines the question of history in Southwest archaeology in two senses. First, it traces the intellectual history of research in the region: from the nineteenth-century inauguration of Southwest archaeology as an extension of American military conquest, to the museum-oriented expeditions of the turn of the century, to the scientific advances and the growth of culture resource management during the twentieth century, to the impacts of Indigenous critiques and the development of collaborative approaches most recently. Second, the chapter explores the shifting status of “history” as a central goal of archaeological practice. How have archaeologists constructed—or resisted—narratives to account for the contingent unfolding of Indigenous and colonial societies in the region? What bodies of method and theory have guided these efforts? In addressing these questions, the chapter marks and participates in a growing historical turn in Southwest archaeology.
Mimbres Archaeology
Authors: Nelson Margaret C. , Gilman Patricia A.
Published: September 2017

The Mimbres cultural tradition once dominated southwestern New Mexico and adjacent areas, and is best known for intricate and beautiful pottery with black designs painted on a white background. The apex of population and tradition—1000–1130 ce—is labeled the Mimbres Classic period. Several major changes distinguish this period from earlier Pithouse periods, including the appearance of the first pueblos in the southern Southwest, increased population, change from enclosed to open ritual spaces, elaboration of black-on-white pottery, and a shift in pan-regional connections from west with the people of the Hohokam region to south into Mesoamerica. This chapter describes these trends and their implications. It then explores three research themes that have contributed to this cultural tradition and to broader understandings of society, ecology, and worldview: human-environment interactions; organizational variation of large pueblos, room layouts, ritual practices, and ceramic production; and the representational and geometric black-on-white pottery.
Preclassic Hohokam
Authors: Craig Douglas B. , Woodson M. Kyle
Published: September 2017

The establishment of the first permanent farming villages in the southern Southwest coincided with the emergence of the Hohokam cultural tradition. This chapter examines the environmental, demographic, and social processes that shaped the development of Hohokam culture. Special attention is paid to the timing and tempo of cultural change across the region. Three periods of rapid change are discussed—the first associated with the establishment of permanent villages (ca. 500 ce), the second associated with the spread of the ball court system (ca. 800 ce), and the third associated with the collapse of the ball court system (ca. 1050–1100 ce). The conditions that affected the operation and management of the largest irrigation works in pre-Hispanic North America are also discussed.
Sonoran Pre-Hispanic Traditions
Authors: Villalpando Elisa , McGuire Randall H.
Published: September 2017

The international border between the United States and Mexico has no meaning for the Aboriginal history of the Southwest/Northwest. It has, however, greatly limited the amount of archaeology done in northern Mexico. Since the 1980s, Mexican and U.S. archaeologists have done increasing amounts of research in the Mexican state of Sonora. Here they have developed an international collaborative practice of archaeology unique in North America. Sonora has a rich archaeological record that includes Paleoindian and Archaic sites. This chapter focuses on the agricultural peoples of Sonora, beginning with the Early Agricultural site of La Playa. Archaeologists have defined six ceramic period archaeological traditions in the state (Central Coast, Trincheras, Casas Grandes, Río Sonora, Huatabampo, and Serrana). Contrary to earlier interpretations of these traditions as extensions of events, processes, and cultures found to the south or the north, contemporary archaeology is demonstrating them to be the results of complex local developments.
The Zuni/Cibola Region
Authors: Peeples Matthew A. , Schachner Gregson , Kintigh Keith W.
Published: September 2017

The Zuni/Cibola region of eastern Arizona and western New Mexico was the setting for some of the earliest formal archaeological investigations in the U.S. Southwest. From the outset, research in the region has been regional in scope, focusing in particular on issues of population movement, community organization, and social identity. Importantly, although the Cibola region is often treated as a single unit of analysis, the regional boundaries are crosscut by broader distinctions between the Anasazi or Ancestral Pueblo culture area to the north and the Mogollon culture area to the south. The apparent complexity of social boundaries in the Cibola region reflects a high degree of mobility and fluid social organization. Due in part to this complexity, the Cibola region has played a major role in conceptualizations of social and cultural identity in the Southwest for both archaeological research and cultural heritage legislation.
Ndee (Apache) Archaeology
Authors: Welch John R. , Herr Sarah A. , Laluk Nicholas C.
Published: September 2017

Despite abundant historical interest in Apache subjugation and early reservation periods, Apache persists as a lacuna in Southwest archaeology. Vexing conceptual and practical challenges to site identification and analyses, coupled with a lack of research specifically focused on Apache histories, regions, and material cultures, have retarded the creation of archaeological knowledge comparable or even complementary to the richness and diversity of Apache oral traditions and ethnographies. These challenges are being confronted as archaeologists integrate ethnographic data and collaborations with Apache culture bearers and community leaders to address Apache chronologies, identities and ethnogeneses, landscapes, and heritages. This chapter selectively reviews Southern Athapaskan culture history and previous research, then provides a data-based discussion of pre-reservation Western Apache archaeology. The conclusion recommends problem-focused and collaborative studies of interest to both Apache and academic scholars.
Hunting Technologies
Authors: Whittaker John C. , Bryce William D.
Published: September 2017

The American Southwest has an unusually rich record of pre-colonial hunting. Projectile points reflect technological change, and can serve as chronological and social markers, but dry preservation also allows direct study of bow and atlatl propulsion systems. Other organic artifacts, including nets, snares, and clubs, reflect the importance of mostly small game in pre-colonial diets and society. Faunal remains, coprolites, and iconography enlarge the record, and continuities with descendant cultures allow unusually good interpretation of hunting practices. Using archaeological data and ethnographic parallels, this chapter discusses the various intentional and opportunistic hunting technologies used through time to procure faunal resources.
Iconography
Authors: Munson Marit K. , Hays-Gilpin Kelley
Published: September 2017

Images from archaeological sites are often engaging, sometimes mysterious, and always seem full of potential for insight into the lives and thoughts of people from the past. Unfortunately, most research into archaeological images relies on a narrow range of art historical methods and on parallels with ethnographic information. These approaches are valuable, but unnecessarily limited. In this chapter, we encourage researchers to expand their understanding of images, exploring how perceptual and social theories of pictures shape our understanding of meaning and discussing the benefits and drawbacks of formal, informed, and artifactual approaches to studying pictures. We also review major temporal and cultural patterns in image traditions in the Southwest, illustrating how iconography yields important insights into cosmologies, values, the advent and spread of religious movements, macro regional interactions, and social dynamics in the past.
Agricultural Landscapes
Authors: Anschuetz Kurt , Camilli Eileen L. , Banet Christopher D.
Published: September 2017

The discussion in this chapter is based on the premise that agricultural landscapes are the foundations of the economies, social organizations, and cultural identities of farming communities. It reviews selected archaeological districts between Sonora and the northern Rio Grande in which technologically diverse agricultural features, including trincheras, terraces, rock-bordered grids, gravel mulches, and canals, are well documented. This examination shows that large-scale field complexes, including those dependent on canal irrigation, are widespread throughout the pre-colonial North American Southwest, with some dating to the Late Archaic. Consideration of the Tewa Basin of north-central New Mexico as a case study introduces the idea that shrines are other essential agricultural landscape features, which possess the potential to contribute toward fuller understandings of farming settlement dynamics.
Spirits
Authors: Van Keuren Scott , Walker William H.
Published: September 2017

This chapter explores how the lives of ancient peoples in the Southwest were guided by their engagement with spirit worlds. From artifacts to architecture, the material record reflects visions of the universe, mythological narratives, and otherworldly entities. As archaeology has turned its attention to ancient religion and ritual, Southwest scholars are expanding their interpretations of these central dimensions of ancient ecologies. This theoretical turn reflects broader changes in the field as well as collaborations with descendant communities. The chapter builds on contemporary theory as well as classic ethnographies to show how spirit worlds may have been engaged and materialized in the ancient Southwest.
Path Dependence
Authors: Hegmon Michelle
Published: September 2017

Path dependence concepts, thus far, have seen little application in archaeology, but they have great potential. At a general level, these concepts provide tools for theorizing historical sequences, such as patterns of settlement on a landscape and divergent historical traditions. Potential applications include issues of historical contingency in the late Rio Grande, settlement in the Mesa Verde region, and divergent trajectories in the post-Chaco period. Specific concepts from path dependence theory, including lock-in and critical junctures, are illustrated by an analysis of the growth of Hohokam irrigation, which exhibited a path-dependent trajectory. As archaeological study of path dependence builds awareness of the importance of decision-making on the future, it contributes to difficult decision-making in today’s world.
Use of Electronic Tablets for Patient Education on Flushing Peripherally Inserted Central Catheters
Authors: Petroulias Patricia L.
Published: September 2017

The purpose of this study was to examine the efficacy of using an electronic tablet to provide patient education for flushing peripherally inserted central catheters (PICCs) as a way to reduce the incidence of occlusion. Eleven patients, newly diagnosed with cancer, participated in a pilot study that used a video on PICC flushing and remote coaching using FaceTime (Apple, Cupertino, CA) to teach patients how to maintain their PICCs in their homes. At the end of the 6-week intervention, no adverse outcomes (occlusions or infections) were noted among the patients who participated in the study.
Clinicopathologic Diversity of Undifferentiated Sarcoma With BCOR-CCNB3 Fusion
Authors: Matsuyama Atsuji , Shiba Eisuke , Umekita Yoshihisa , Nosaka Kanae , Kamio Takihiro , Yanai Hiroyuki , Miyasaka Chika , Watanabe Reiko , Ito Ichiro , Tamaki Tomoko , Hayashi Shinichi , Hisaoka Masanori
Published: September 2017

Undifferentiated sarcoma harboring the BCOR-CCNB3 fusion is characterized by its predilection to affect skeletons of adolescent males, cellular small round/spindle cell morphology, and CCNB3 immunoreactivity. We analyzed 11 cases of BCOR-CCNB3 sarcoma, 10 of which were identified in a reverse transcription-polymerase chain reaction–based screen of 85 patient samples recorded in our database as unclassified small round or spindle cell sarcomas. BCOR rearrangements were confirmed by fluorescence in situ hybridization in 8 tumors. All patients were males aged between 6 and 31 years. In addition to 5 tumors in soft tissue and 4 in the axial or appendicular skeletons, which are typical locations, a tumor was located in the paranasal sinus and another in the lung. Microscopically, the tumors comprised proliferating atypical spindle and/or small round cells with diverse morphologic features such as small concentric whorls, myxoid stroma, a hemangiopericytomatous appearance, and/or hyalinized collagen resembling a solitary fibrous tumor, and angiomatous or slit-like spaces containing extravasated erythrocytes. Tumor cells were immunoreactive to CCNB3 (9/11), BCOR (10/10), TLE1 (6/10), bcl-2 (9/11), CD99 (8/10), CD56 (8/10), c-kit (4/10), and cyclin D1 (10/10). In an immunohistochemical analysis of an additional 412 small round or spindle cell tumors, CCNB3 was detected in 6 (1.5%) and BCOR in 18 (4.4%). Our analysis highlights the varying clinicopathologic features of this tumor, which partially overlap with other small round or spindle cell tumors, including solitary fibrous tumor and vascular tumors. Because CCNB3 and BCOR immunohistochemistry lacks adequate sensitivity and specificity, a molecular genetic approach remains essential for diagnosis.
PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma
Authors: Chapel David B. , Husain Aliya N. , Krausz Thomas , McGregor Stephanie M.
Published: September 2017

Distinguishing malignant peritoneal mesothelioma (MPM) from serous carcinoma involving the peritoneum remains a diagnostic challenge, particularly in small biopsy and cytology specimens. In this distinction, PAX8 expression has been regarded as a specific marker of serous carcinoma. In addition, BAP1 loss is reportedly specific to MPM, in the distinction from both benign mesothelial lesions and ovarian serous tumors (OSTs). Using immunohistochemistry, we examined PAX8 and BAP1 expression in 27 MPMs, 25 cases of benign mesothelium, and 45 OSTs. Five MPMs were PAX8+ (5/27, 18%), while 8 cases of benign mesothelium expressed PAX8 (8/25, 32%). PAX8 expression in mesothelium was significantly more common in women than in men (P=0.01). Sixteen MPMs exhibited BAP1 loss (16/25, 64%), while BAP1 was retained in all benign mesothelium and all OSTs. All cases of PAX8+ mesothelium were negative for expression of estrogen receptor. These data show that PAX8 is expressed in both benign and malignant mesothelium, and that BAP1 loss is highly specific for MPM, in the differential with both benign mesothelial proliferations and OTSs. These results also have implications for primary diagnosis and for pathologic staging of OST. Caution should be applied when PAX8 expression is used to distinguish mesothelial and serous proliferations, and BAP1 loss may be confirmatory in cases where mesothelioma is favored.
“Atypical” Pleomorphic Lipomatous Tumor
Authors: Creytens David , Mentzel Thomas , Ferdinande Liesbeth , Lecoutere Evelyne , van Gorp Joost , Atanesyan Lilit , de Groot Karel , Savola Suvi , Van Roy Nadine , Van Dorpe Jo , Flucke Uta
Published: September 2017

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma–like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term “atypical” pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related lesions that form a spectrum (atypical spindle cell/pleomorphic lipomatous tumor).
Desmoplastic Pattern at the Tumor Front Defines Poor-prognosis Subtypes of Colorectal Cancer
Authors: Ueno Hideki , Kanemitsu Yukihide , Sekine Shigeki , Ishiguro Megumi , Ito Eisaku , Hashiguchi Yojiro , Kondo Fukuo , Shimazaki Hideyuki , Mochizuki Satsuki , Kajiwara Yoshiki , Shinto Eiji , Yamamoto Junji
Published: September 2017

Although recent findings of cancer biology research indicate that prognostic power arises from genes expressed by stromal cells rather than epithelial cells, desmoplastic reaction (DR) has not been completely examined as a prognostic marker for colorectal cancer. A pathologic review of 821 stage II and III patients who underwent R0 resection for colorectal cancer at 4 independent institutions was conducted. DR was classified as mature, intermediate, or immature based on the existence of hyalinized keloid-like collagen and myxoid stroma at the extramural desmoplastic front. Totally, 325, 282, and 214 patients were classified as having mature, intermediate, and immature DR, respectively. DR significantly influenced the recurrence rate in the liver, lung, and peritoneum (P≤0.0001 to 0.01). Five-year relapse-free survival (RFS) rate was the highest in the mature group (85.7%), followed by the intermediate (77.3%) and immature (50.4%) groups. A significant adverse impact of immature stroma on RFS was observed in subset analyses of the 4 institutions. Multivariate analysis revealed that DR, along with T and N stages, is an independent prognostic factor. On the basis of Harrell’s concordance index, the prognostic power of DR categorization (0.67) in stratifying RFS was greater than any other conventional prognostic factors, including TNM (0.64), N (0.62) and T stages (0.59), venous invasion (0.59), and tumor grade (0.54). Characterizing DR based on the histologic products of activated fibroblasts is valuable for evaluating prognostic outcomes. To our knowledge, this is the first study reporting a greater prognostic power of histology of the fibrotic stroma than that of tumor factors.
Effectiveness of Shortwave Diathermy for Subacromial Impingement Syndrome and Value of Night Pain for Patient Selection
Authors: Yilmaz Kaysin Meryem , Akpinar Pinar , Aktas Ilknur , Unlü Ozkan Feyza , Silte Karamanlioglu Duygu , Cagliyan Hartevioglu Hulya , Vural Nazan
Published: September 2017

Objective

The aim of this study was to investigate the effectiveness of short wave diathermy (SWD) in patients with subacromial impingement syndrome.

Design

In this double-blinded, randomized, placebo-controlled trial, 57 patients (aged 35–65 yrs) were classified into night pain positive (NP[+]) (n = 28) and night pain negative (NP[−]) (n = 29) groups. Both groups were randomly assigned to SWD (NP[+], n = 14; NP[−], n = 14) and sham (NP[+], n = 15; NP[−], n = 14) subgroups. Visual analog scale, Constant-Murley Scale (CS), and Shoulder Disability Questionnaire (SDQ) scores were used for evaluation.

Results

There was only a significant difference in pain with activity at 1-mo (mean difference [MD], −1.65; 95% confidence interval, −3.01 to −0.28]) and 2-mo evaluations (MD, −2.1; 95% confidence interval, −3.51 to −0.69) between SWD versus sham groups. In the NP(+) SWD group, the CS pain score was significantly higher than in the NP(+) sham group at all evaluations after treatment. At 1 mo, the NP(−) SWD group showed significantly better pain, strength, total CS, and SDQ scores than the NP(−) sham group. At 2 mos, the pain, range of motion, strength, and total CS and SDQ scores were better in the NP(−) SWD group than in the NP(−) sham group (P < 0.05).

Conclusions

Short wave diathermy is more effective in subacromial impingement syndrome without NP.
Application of Transcranial Color Doppler Ultrasonography for Assessing Middle Cerebral Arteries in Rheumatoid Arthritis
Authors: Chen Qiuyue , Li Shilin , Lv Guorong , Zhao Yanchun
Published: September 2017

To assess the role of ultrasonography for assessing middle cerebral arteries (MCAs) in rheumatoid arthritis (RA). Middle cerebral arteries of 32 RA patients and 32 healthy volunteers were examined by ultrasonography. Peak systolic blood flow velocity (PSV), end-diastolic velocity, and resistance index (RI) of MCA were measured using Doppler ultrasound. Results were expressed as mean ± SD. No significant difference in peak systolic velocity was obtained between RA patients (52.44 ± 19.56 cm/s) and healthy volunteers (51.59 ± 16.83 cm/s, P > 0.05). End-diastolic velocity in RA patients was significantly lower (15.41 ± 5.44 cm/s vs 24.54 ± 8.45 cm/s, P < 0.01) and RI markedly higher (0.66 ± 0.10 vs 0.60 ± 0.06, P < 0.05) compared with control values. Resistance index in 32 RA patients increased with disease duration (2 months to 31 years), from a median value of 0.350 to 0.830; there was a strong correlation between RI and disease duration (r = 0.965, P < 0.05). A point of 0.64 in receiver operating characteristic curve was chosen as the cutoff point, and the area under the curve was 0.918. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 90.6%, 87.5%,87.9%, 90.3%, and 89.1%, respectively. Color Doppler ultrasound in RA patients with hemodynamic changes of MCAs could be a relatively sensitive tool for the detection of cerebral atherosclerotic lesions. This could enable timely intervention for early clinical reference.
Effect of aspirin on tumour cell colony formation and evolution
Authors: Wodarz Dominik , Goel Ajay , Boland C. Richard , Komarova Natalia L.
Published: September 2017

Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the
in vitro
growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to
in vivo
settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection.
The rapid
in vivo
evolution of
Pseudomonas aeruginosa
in ventilator-associated pneumonia patients leads to attenuated virulence
Authors: Wang Ke , Chen Yi-qiang , Salido May M. , Kohli Gurjeet S. , Kong Jin-liang , Liang Hong-jie , Yao Zi-ting , Xie Yan-tong , Wu Hua-yu , Cai Shuang-qi , Drautz-Moses Daniela I. , Darling Aaron E. , Schuster Stephan C. , Yang Liang , Ding Yichen
Published: September 2017

Pseudomonas aeruginosa
is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways,
P. aeruginosa
could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat
P. aeruginosa
infections. In this study, 25
P. aeruginosa
isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the
in vivo
evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped
P. aeruginosa
genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of
lasR
and
mpl
, and a pyoverdine-deficient phenotype. Specifically,
lasR
encodes one of the major transcriptional regulators in quorum sensing, whereas
mpl
encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that
P. aeruginosa
isolated at late stages of VAP infections produce less elastase and are less virulent
in vivo
than their earlier isolated counterparts, suggesting the short-term
in vivo
evolution of
P. aeruginosa
leads to attenuated virulence.
Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression
Authors: Perland Emelie , Bagchi Sonchita , Klaesson Axel , Fredriksson Robert
Published: September 2017

Solute carriers (SLCs) are vital as they are responsible for a major part of the molecular transport over lipid bilayers. At present, there are 430 identified SLCs, of which 28 are called atypical SLCs of major facilitator superfamily (MFS) type. These are MFSD1, 2A, 2B, 3, 4A, 4B, 5, 6, 6 L, 7, 8, 9, 10, 11, 12, 13A, 14A and 14B; SV2A, SV2B and SV2C; SVOP and SVOPL; SPNS1, SPNS2 and SPNS3; and UNC93A and UNC93B1. We studied their fundamental properties, and we also included CLN3, an atypical SLC not yet belonging to any protein family (Pfam) clan, because its involvement in the same neuronal degenerative disorders as MFSD8. With phylogenetic analyses and bioinformatic sequence comparisons, the proteins were divided into 15 families, denoted atypical MFS transporter families (AMTF1-15). Hidden Markov models were used to identify orthologues from human to
Drosophila melanogaster
and
Caenorhabditis elegans
. Topology predictions revealed 12 transmembrane segments (for all except CLN3), corresponding to the common MFS structure. With single-cell RNA sequencing and
in situ
proximity ligation assay on brain cells, co-expressions of several atypical SLCs were identified. Finally, the transcription levels of all genes were analysed in the hypothalamic N25/2 cell line after complete amino acid starvation, showing altered expression levels for several atypical SLCs.
Interactions of the
Bacillus subtilis
DnaE polymerase with replisomal proteins modulate its activity and fidelity
Authors: Paschalis Vasileios , Le Chatelier Emmanuelle , Green Matthew , Képès François , Soultanas Panos , Janniere Laurent
Published: September 2017

During
Bacillus subtilis
replication two replicative polymerases function at the replisome to collectively carry out genome replication. In a reconstituted
in vitro
replication assay, PolC is the main polymerase while the lagging strand DnaE polymerase briefly extends RNA primers synthesized by the primase DnaG prior to handing-off DNA synthesis to PolC. Here, we show
in vivo
that (i) the polymerase activity of DnaE is essential for both the initiation and elongation stages of DNA replication, (ii) its error rate varies inversely with PolC concentration, and (iii) its misincorporations are corrected by the mismatch repair system post-replication. We also found that the error rates in cells encoding mutator forms of both PolC and DnaE are significantly higher (up to 15-fold) than in PolC mutants.
In vitro
, we showed that (i) the polymerase activity of DnaE is considerably stimulated by DnaN, SSB and PolC, (ii) its error-prone activity is strongly inhibited by DnaN, and (iii) its errors are proofread by the 3′ > 5′ exonuclease activity of PolC in a stable template-DnaE–PolC complex. Collectively our data show that protein–protein interactions within the replisome modulate the activity and fidelity of DnaE, and confirm the prominent role of DnaE during
B. subtilis
replication.
Architecture of crossed-lamellar bivalve shells: the southern giant clam (Tridacna derasa, Röding, 1798)
Authors: Agbaje O. B. A. , Wirth R. , Morales L. F. G. , Shirai K. , Kosnik M. , Watanabe T. , Jacob D. E.
Published: September 2017

Tridacna derasashells show a crossed lamellar microstructure consisting of three hierarchical lamellar structural orders. The mineral part is intimately intergrown with 0.9 wt% organics, namely polysaccharides, glycosylated and unglycosylated proteins and lipids, identified by Fourier transform infrared spectrometry. Transmission electron microscopy shows nanometre-sized grains with irregular grain boundaries and abundant voids. Twinning is observed across all spatial scales and results in a spread of the crystal orientation angles. Electron backscatter diffraction analysis shows a strong fibre texture with the [001] axes of aragonite aligned radially to the shell surface. The aragonitic [100] and [010] axes are oriented randomly around [001]. The random orientation of anisotropic crystallographic directions in this plane reduces anisotropy of the Young's modulus and adds to the optimization of mechanical properties of bivalve shells.
Huygens’ clocks revisited
Authors: Willms Allan R. , Kitanov Petko M. , Langford William F.
Published: September 2017

In 1665, Huygens observed that two identical pendulum clocks, weakly coupled through a heavy beam, soon synchronized with the same period and amplitude but with the two pendula swinging in opposite directions. This behaviour is now called anti-phase synchronization. This paper presents an analysis of the behaviour of a large class of coupled identical oscillators, including Huygens' clocks, using methods of equivariant bifurcation theory. The equivariant normal form for such systems is developed and the possible solutions are characterized. The transformation of the physical system parameters to the normal form parameters is given explicitly and applied to the physical values appropriate for Huygens' clocks, and to those of more recent studies. It is shown that Huygens' physical system could only exhibit anti-phase motion, explaining why Huygens observed exclusively this. By contrast, some more recent researchers have observed in-phase or other more complicated motion in their own experimental systems. Here, it is explained which physical characteristics of these systems allow for the existence of these other types of stable solutions. The present analysis not only accounts for these previously observed solutions in a unified framework, but also introduces behaviour not classified by other authors, such as a synchronized toroidal breather and a chaotic toroidal breather.
Interacting effects of wildlife loss and climate on ticks and tick-borne disease
Authors: Titcomb Georgia , Allan Brian F. , Ainsworth Tyler , Henson Lauren , Hedlund Tyler , Pringle Robert M. , Palmer Todd M. , Njoroge Laban , Campana Michael G. , Fleischer Robert C. , Mantas John Naisikie , Young Hillary S.
Published: September 2017

Both large-wildlife loss and climatic changes can independently influence the prevalence and distribution of zoonotic disease. Given growing evidence that wildlife loss often has stronger community-level effects in low-productivity areas, we hypothesized that these perturbations would have interactive effects on disease risk. We experimentally tested this hypothesis by measuring tick abundance and the prevalence of tick-borne pathogens (
Coxiella burnetii
and
Rickettsia
spp
.
) within long-term, size-selective, large-herbivore exclosures replicated across a precipitation gradient in East Africa. Total wildlife exclusion increased total tick abundance by 130% (mesic sites) to 225% (dry, low-productivity sites), demonstrating a significant interaction of defaunation and aridity on tick abundance. When differing degrees of exclusion were tested for a subset of months, total tick abundance increased from 170% (only mega-herbivores excluded) to 360% (all large wildlife excluded). Wildlife exclusion differentially affected the abundance of the three dominant tick species, and this effect varied strongly over time, likely due to differences among species in their host associations, seasonality, and other ecological characteristics. Pathogen prevalence did not differ across wildlife exclusion treatments, rainfall levels, or tick species, suggesting that exposure risk will respond to defaunation and climate change in proportion to total tick abundance. These findings demonstrate interacting effects of defaunation and aridity that increase disease risk, and they highlight the need to incorporate ecological context when predicting effects of wildlife loss on zoonotic disease dynamics.
Exceptional preservation and the fossil record of tetrapod integument
Authors: Eliason Chad M. , Hudson Leah , Watts Taylor , Garza Hector , Clarke Julia A.
Published: September 2017

The fossil record of exceptionally preserved soft tissues in Konservat-Lagerstätten provides rare yet significant insight into past behaviours and ecologies. Such deposits are known to occur in bursts rather than evenly through time, but reasons for this pattern and implications for the origins of novel structures remain unclear. Previous assessments of these records focused on marine environments preserving chemically heterogeneous tissues from across animals. Here, we investigate the preservation of skin and keratinous integumentary structures in land-dwelling vertebrates (tetrapods) through time, and in distinct terrestrial and marine depositional environments. We also evaluate previously proposed biotic and abiotic controls on the distribution of 143 tetrapod Konservat-Lagerstätten from the Permian to the Pleistocene in a multivariate framework. Gap analyses taking into account sampling intensity and distribution indicate that feathers probably evolved close to their first appearance in the fossil record. By contrast, hair and archosaur filaments are weakly sampled (five times less common than feathers), and their origins may significantly pre-date earliest known occurrences in the fossil record. This work suggests that among-integument variation in preservation can bias the reconstructed first origins of integumentary novelties and has implications for predicting where, and in what depositional environments, to expect further discoveries of exquisitely preserved tetrapod integument.
Fearful but not happy expressions boost face detection in human infants
Authors: Bayet Laurie , Quinn Paul C. , Laboissière Rafael , Caldara Roberto , Lee Kang , Pascalis Olivier
Published: September 2017

Human adults show an attentional bias towards fearful faces, an adaptive behaviour that relies on amygdala function. This attentional bias emerges in infancy between 5 and 7 months, but the underlying developmental mechanism is unknown. To examine possible precursors, we investigated whether 3.5-, 6- and 12-month-old infants show facilitated
detection
of fearful faces in noise, compared to happy faces. Happy or fearful faces, mixed with noise, were presented to infants (
N
= 192), paired with pure noise. We applied multivariate pattern analyses to several measures of infant looking behaviour to derive a criterion-free, continuous measure of face detection evidence in each trial. Analyses of the resulting psychometric curves supported the hypothesis of a detection advantage for fearful faces compared to happy faces, from 3.5 months of age and across all age groups. Overall, our data show a readiness to detect fearful faces (compared to happy faces) in younger infants that developmentally precedes the previously documented attentional bias to fearful faces in older infants and adults.
Sox4drivesAtoh1-independent intestinal secretory differentiation toward tuft and enteroendocrine fates
Authors: Gracz Adam D , Samsa Leigh Ann , Fordham Matthew J , Trotier Danny C , Zwarycz Bailey , Lo Yuan-Hung , Bao Katherine , Starmer Joshua , Shroyer Noah F , Reinhardt R. Lee , Magness Scott T
Published: September 2017

Background & Aims

The intestinal epithelium is maintained by intestinal stem cells (ISCs), which produce post-mitotic absorptive and secretory epithelial cells. Initial fate specification toward enteroendocrine, goblet, and Paneth cell lineages is dependent onAtoh1, a master regulator of secretory differentiation. However, the origin of tuft cells, which participate in Type II immune responses to parasitic infection, is less clear and appears to occur in anAtoh1-independent manner. Here we examine the role ofSox4in ISC proliferation and differentiation.

Methods

We used mice with intestinal epithelial-specific conditional knockout ofSox4(Sox4fl/fl:vilCre; Sox4cKO) to study the role ofSox4in the small intestine. Crypt- and single cell-derived organoids were used to assay proliferation and ISC potency between control and Sox4cKO mice. Lineage allocation and genetic consequences ofSox4ablation were studied by immunofluorescence, RT-qPCR, and RNA-seq.In vivoinfection with helminths andin vitrocytokine treatment in primary intestinal organoids were used to assess tuft cell hyperplasia in control and Sox4cKO samples.Atoh1GFPreporter mice and single cell RNA-seq (scRNA-seq) were used to determine co-localization of SOX4 andAtoh1. Wild-type and inducibleAtoh1knockout (Atoh1fl/fl:vilCreER; Atoh1iKO) organoids carrying an inducibleSox4overexpression vector (Sox4OE) were used to determine the role ofAtoh1inSox4driven secretory differentiation.

Results

Loss ofSox4impairs ISC function and secretory differentiation, resulting in decreased numbers of enteroendocrine and tuft cells. In wild-type mice, SOX4+ cells are significantly upregulated following helminth infection coincident with tuft cell hyperplasia.Sox4is activated by IL13in vitroand Sox4cKO knockout mice demonstrate impaired tuft cell hyperplasia and parasite clearance following infection with helminths. A subset ofSox4-expressing cells colocalize withAtoh1and enteroendocrine markers by scRNA-seq, whileSox4+/Atoh1-cells correlate strongly with tuft cell populations. Gain-of-function studies in primary organoids demonstrate thatSox4is sufficient to drive both enteroendocrine and tuft cell differentiation, and can do so in the absence ofAtoh1.

Conclusion

Our data demonstrate thatSox4promotes enteroendocrine and tuft cell lineage allocation independently ofAtoh1. These results challenge long-standing views ofAtoh1as the sole regulator of secretory differentiation in the intestine and are relevant for understanding host epithelial responses to parasitic infection.