bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal Amyloid Load in Mild Cognitive Impairment: The Effect of Reducing the PiB‐PET Threshold
Authors: Ismail Rola , Parbo Peter , Hansen Kim V. , Schaldemose Jeppe L. , Dalby Rikke B. , Tietze Anna , Kjeldsen Pernille L. , la Cour Sanne Hage , Qvist Per , Gottrup Hanne , Eskildsen Simon F. , Brooks David J.
Published: May 2019

BACKGROUND AND PURPOSE

In vivo detection of β‐amyloid (Aβ) plaques in Alzheimer's disease (AD) is now possible with 11C‐PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4‐1.5 has been used to categorize at‐risk subjects as “amyloid‐positive” and “amyloid‐negative.” It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11C‐PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally.

METHODS

We serially determined the cortical amyloid load with 11C‐PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases.

RESULTS

Twenty‐four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty‐seven “raised amyloid” MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow‐up period.

CONCLUSION

Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.
Incidence of abutment screw failure of single or splinted implant prostheses: A review and update on current clinical status
Authors: Katsavochristou Anastasia , Koumoulis Dimitrios
Published: May 2019

Osseointegrated implants have been widely used for decades with high survival and success rates. However, mechanical complications continue to be reported in the literature, and their clinical management can be often very challenging for the clinician while there is no consensus on the ideal management. The aim of this manuscript was to review the risk factors of abutment screw complications, to identify the most recent incidence of screw failure in the clinical setting and report on the methodology used and the outcome of intervention. Clinical studies and reports were reviewed that reported on abutment screw looseness and/or fracture. A search of the electronic database PUBMED was conducted in November 2018, including manuscripts published in English from 2004 to 2018. Study selection: animal studies, narrative reviews, expert opinions and communications/letters were excluded. Further exclusion criteria included reports on occlusal prosthetic screws and fracture of abutments, and reports that did not provide adequate data. A total of 12 manuscripts were finally included that reported on single implant crowns or 2‐unit implant fixed dental prosthesis. To conclude, the most current abutment screw loosening incidence ranges between 7% and 11%, while the abutment screw fracture incidence was found to be 0.6%. The majority reported on fracture of the screw body. Screw loosening or fracture was often located at the first molar restored area, while the maxillary central incisor area was also reported as an area that presented screw fracture. No single abutment screw failure management can be identified as the ideal treatment approach.
“Those foreigners ruin everything here”: Interactional functions of ethnic labelling among pupils in the Netherlands
Authors: van de Weerd Pomme
Published: May 2019

This paper contributes to a deeper understanding of ethnic labelling practices by examining their interactional functions among secondary school pupils in Venlo, the Netherlands. Pupils with migration backgrounds often labelled themselves and others “Turk,” “Moroccan,” or “foreigner,” and labelled others “Dutch.” The paper highlights that ethnic labelling can be understood not only as identity construction, but also as interactional work. I build on membership categorization analysis (MCA), complemented by conversation analysis (CA), to analyse how pupils’ use of ethnic labels evoked an expert role which altered interactants’ power positions; and how, often, pupils engaged in jocular mockery with ethnic labels and in that way mitigated the effects of exclusionary and stigmatizing discourses about people with migration backgrounds. Finally, I argue that pupils’ labelling practices had locally occasioned meanings and functions, but that they ultimately reflect wider‐spread systems of categorization and marginalization of people with migration backgrounds in the Netherlands.
Financing Development Projects: An Approach by Civil Society Organizations
Authors: Ochman Marta
Published: May 2019

This article analyzes how financing rules in civil society organizations affect their ability to promote development. The hypothesis proposes that there is a contradiction between the expectations of social innovation, and rules of competition for resources that respond to the efficiency and control paradigms. As a result, Civil Society Organizations have a limited ability to promote projects with a long‐term effect, and civil society’s autonomy is undermined. This study is based on a phenomenological approach and was carried out using semi‐structured interviews with nine organizations working in Mexico.
Having It Both Ways: Can Latin American Spend More Money on Innovation and Reduce Income Inequality?
Authors: Soh Adrian B. L.
Published: May 2019

This article examines if Latin American nations would be helped by a participatory budgeting scheme for science at a time when their traditional exports of commodities are facing low prices; there is a need for industrial diversification; and there are high private‐debt levels, persistent poverty and inequality, and fiscal problems. Attempting to solve these issues has threatened the progress of science and technology policies over the last decade in Latin America at a time when countries such as China, Korea, Israel, and Finland were becoming increasingly competitive in science and technology. The article further examines the political pressures and resource competition that science and technology funding faces in Latin America, showing how a participatory budgeting scheme for science would invest in technology startups, remove reliance on taxation for science and technology funding, manage risk, supplement the incomes of citizens, and grant funds for basic research in Latin America. Finally, the article shows how the scheme would facilitate cooperation between Latin American business, the international science community, the general public, and government through investing in rather than taxing technology startups, while making sure that the general public receives more of a share of the economic gains from scientific discoveries in Latin America.
Legislators and Regional Organizations: The Issue of Legitimacy
Authors: Mace Gordon , Lockhart Nicolas Falomir
Published: May 2019

Recent scholarship has argued that there has been an opening up of international and regional organizations toward transnational actors since the end of the Cold War, as a result of increased democratization, which is generally considered as a positive contribution to the legitimacy of these organizations. Yet it remains unclear how generalized the opening up has been in terms of regions and category of actors. The role of legislators, particularly outside the European Union, remains understudied even though their presence in regional organizations has increased over the past three decades. This article seeks to fill this void partially by way of a comparative analysis of the role of legislators using the Organization of American States and the Southern Common Market as case studies. The first part of the article offers an overview of the literature and presents our research design. We then proceed with a comparative analysis of the role of legislators at the input, throughput, and output stages of the legitimation process. We conclude with a general assessment of the contribution of legislators as dispensers of legitimacy for regional organizations in the Americas.
Evolution and Effects of the Legal and Regulatory Framework on Microfinance in Brazil
Authors: Nayak Bhabani Shankar , da Silva Ronaldo Vieira
Published: May 2019

This article argues that a strong legal and regulatory framework can contribute to the expansion of microfinance in Brazil. First, it outlines the regulatory framework in the enhancement of microfinance in the country; it then reviews different patterns of regulation and supervision for the success of this microfinance. The findings suggest mixed results; a stringent regulatory regime and rules have limited the growth of most microfinance institutions, and the segment has become very dependent on public funding. There is a need for the right balance between freedom for the sustainable growth of microfinance institutions, and a correct dosage of monitoring to maintain public confidence in them. The article outlines the defining characteristics of the Brazilian microfinance sector and discusses the possible gaps in the current regulatory framework, as well as the best practices that could contribute to an effective supervision and regulation of microfinance in Brazil.
The Crisis in Venezuela: A New Chapter, or the Final Chapter?
Authors: Briceño-Ruiz José
Published: May 2019

This paper analyses the current political crisis in Venezuela after the proclamation of Juan Guaido as interim President in January 2019. The main argument here is that current crisis is the most recent chapter a long political crisis that began with rise to power of Hugo Chávez in 1999. A brief historical analysis of the previous chapters of the crisis is done as well an evaluation about the extent to which those previous events influence on current ones. The paper ends with an evalution of the possible scenarios of solution of the crisis and the role that Venezuelan domestic actors and international actors will play.
Phylogeographical and cross‐species transmission dynamics of SAT1 and SAT2 foot‐and‐mouth disease virus in Eastern Africa
Authors: Omondi George , Alkhamis Moh A. , Obanda Vincent , Gakuya Francis , Sangula Abraham , Pauszek Steven , Perez Andres , Ngulu Stephen , van Aardt Richard , Arzt Jonathan , VanderWaal Kim
Published: May 2019

Understanding the dynamics of foot‐and‐mouth disease virus (FMDV), an endemic and economically constraining disease, is critical in designing control programmes in Africa. This study investigates the evolutionary epidemiology of SAT1 and SAT2 FMDV in Eastern Africa, as well as between cattle and wild African buffalo. Bayesian phylodynamic models were used to analyse SAT1 and SAT2 VP1 gene segments collected between 1975 and 2016, focusing on the SAT1 and SAT2 viruses currently circulating in Eastern Africa. The root state posterior probabilities inferred from our analyses suggest Zimbabwe as the ancestral location for SAT1 currently circulating in Eastern Africa (p = 0.67). For the SAT2 clade, Kenya is inferred to be the ancestral location for introduction of the virus into other countries in Eastern Africa (p = 0.72). Salient (Bayes factor >10) viral dispersal routes were inferred from Tanzania to Kenya, and from Kenya to Uganda for SAT1 and SAT2, respectively. Results suggest that cattle are the source of the SAT1 and SAT2 clades currently circulating in Eastern Africa. In addition, our results suggest that the majority of SAT1 and SAT2 in livestock come from other livestock rather than wildlife, with limited evidence that buffalo serve as reservoirs for cattle. Insights from the present study highlight the role of cattle movements and anthropogenic activities in shaping the evolutionary history of SAT1 and SAT2 in Eastern Africa. While the results may be affected by inherent limitations of imperfect surveillance, our analysis elucidates the dynamics between host species in this region, which is key to guiding disease intervention activities.
‘Bumping along’: a qualitative metasynthesis of challenges to interprofessional placements
Authors: O'Leary Noreen , Salmon Nancy , Clifford Amanda , O'Donoghue Michelle , Reeves Scott
Published: May 2019

Context

Interprofessional practice is required to manage complex health care needs globally. It is well established that interprofessional placements (IPP) prepare students to work collaboratively, yet IPP implementation remains limited and disjointed.

Objectives

This review synthesised student, educator and service user perspectives in order to better understand challenges of IPP and provide recommendations for sustainable IPP implementation.

Methods

A systematic metasynthesis of qualitative literature sourced from databases including CINAHL, Embase and PsycINFO was completed. Studies that incorporated student, educator and/or service user perspectives on IPP experiences were included. We focused specifically on factors limiting implementation of IPP. The presage‐process‐product (3P) theory provided the theoretical framework for inductive synthesis of 41 empirical studies. A confidence rating for findings was formulated using CERQual (confidence in evidence from reviews of qualitative research).

Results

We developed three themes, which represent key challenges to IPP becoming embedded in placement culture: (i) thin theoretical foundations underpinned IPP, limiting understanding of the learning processes involved; (ii) implementation relied heavily on individual champions, which curtails investment and sustainability when personnel change, and (iii) students, educators and service users were unsure of the function of IPP and their respective roles, leading to uncertainty along with some negative perceptions of this placement approach.

Conclusions

In line with the 3P theoretical framework, IPP would benefit from explicit connections with educational and change management theories during presage stage IPP requires coordinated leadership and resource investment, and during product stage clear integration of interprofessional learning outcomes in curricula is advised. Addressing the identified challenges across the stages of IPP will support further development of IPP, firmly establishing this approach within placement culture. IPP can them make a significant contribution to the development of a collaborative practice‐ready workforce. This in turn will enhance service user outcomes and safety.
The chemical and visual bases of the pollination of the Neotropical sexually deceptive orchidTelipogon peruvianus
Authors: Martel Carlos , Francke Wittko , Ayasse Manfred
Published: May 2019

Deception of floral visitors in pollination systems is widely distributed among flowering plants. In deceptive systems, the flower (or part of it) or inflorescence mimics either a specific or an unspecific model to attract pollinators.

A previous study showed thatTelipogon peruvianusflowers developed sexual deception for pollination. However, it was unknown which stimuli were playing a role in pollination. Therefore, we aim to throw some light onto these questions using colour and chemical analysis and biotests.

Interestingly, using spectral reflectance, we show here that the flowers present high contrast similar to that produced by a female tachinid fly sitting on a daisy inflorescence, which is used as food resource. We also tested the role of chemical signals in pollinator attraction by collecting floral and female extracts for chemical and electrophysiological analyses, and carried out behavioural tests. For biotests, various treatments, including synthetic mixtures of the electrophysiologically active compounds found in common in females and flowers, have demonstrated thatT. peruvianusflowers mimic the sexual pheromone of their pollinator's females.

Thus, we give evidence thatT. peruvianusflowers mimic a model composed of two organisms. Our study contributes to the understanding of the evolution of deceptive pollination.
Dwelling in the deep – strongly increased root growth and rooting depth enhance plant interactions with thawing permafrost soil
Authors: Blume‐Werry Gesche , Milbau Ann , Teuber Laurenz M. , Johansson Margareta , Dorrepaal Ellen
Published: May 2019

Climate‐warming‐induced permafrost thaw exposes large amounts of carbon and nitrogen in soil at considerable depths, below the seasonally thawing active layer. The extent to which plant roots can reach and interact with these hitherto detached, deep carbon and nitrogen stores remains unknown.

We aimed to quantify how permafrost thaw affects root dynamics across soil depths and plant functional types compared with above‐ground abundance, and potential consequences for plant–soil interactions.

A decade of experimental permafrost thaw strongly increased total root length and growth in the active layer, and deep roots invaded the newly thawed permafrost underneath. Root litter input to soil across all depths was 10 times greater with permafrost thaw. Root growth timing was unaffected by experimental permafrost thaw but peaked later in deeper soil, reflecting the seasonally receding thaw front. Deep‐rooting species could sequester 15N added at the base of the ambient active layer in October, which was after root growth had ceased.

Deep soil organic matter that has long been locked up in permafrost is thus no longer detached from plant processes upon thaw. Whether via nutrient uptake, carbon storage, or rhizosphere priming, plant root interactions with thawing permafrost soils may feed back on our climate both positively and negatively.
The inconspicuous gatekeeper: endophytic Serendipita vermifera acts as extended plant protection barrier in the rhizosphere
Authors: Sarkar Debika , Rovenich Hanna , Jeena Ganga , Nizam Shadab , Tissier Alain , Balcke Gerd U. , Mahdi Lisa K. , Bonkowski Michael , Langen Gregor , Zuccaro Alga
Published: May 2019

In nature, beneficial and pathogenic fungi often simultaneously colonise plants. Despite substantial efforts to understand the composition of natural plant−microbe communities, the mechanisms driving such multipartite interactions remain largely unknown.

Here we address how the interaction between the beneficial root endophyte Serendipita vermifera and the pathogen Bipolaris sorokiniana affects fungal behaviour and determines barley host responses using a gnotobiotic soil‐based split‐root system.

Fungal confrontation in soil resulted in induction of B. sorokiniana genes involved in secondary metabolism and a significant repression of genes encoding putative effectors. In S. vermifera, genes encoding hydrolytic enzymes were strongly induced. This antagonistic response was not activated during the tripartite interaction in barley roots. Instead, we observed a specific induction of S. vermifera genes involved in detoxification and redox homeostasis. Pathogen infection but not endophyte colonisation resulted in substantial host transcriptional reprogramming and activation of defence. In the presence of S. vermifera, pathogen infection and disease symptoms were significantly reduced despite no marked alterations of the plant transcriptional response.

The activation of stress response genes and concomitant repression of putative effector gene expression in B. sorokiniana during confrontation with the endophyte suggest a reduction of the pathogen's virulence potential before host plant infection.
Peptide receptors as cancer drug targets
Authors: Moody Terry W.
Published: May 2019

Neuropeptides function as neuromodulators in the brain, whereby they are released in a paracrine manner and activate G protein–coupled receptors (GPCRs) in adjacent cells. Because neuropeptides are made in, and secreted from, cancer cells, then bind to cell surface receptors, they function in an autocrine manner. Bombesin (BB)‐like peptides synthesized by neuroendocrine tumor small cell lung cancer (SCLC) bind to BB receptors (BBRs), causing phosphatidylinositol turnover and phosphorylation of extracellular signal–regulated kinase (ERK). Phosphorylated ERK enters the nucleus and alters gene expression of SCLC cells, stimulating growth. Vasoactive intestinal peptide (VIP) addition to SCLC cells increases their release rate of BB‐like peptides via activation of VIP receptors (VIPR), leading to activation of adenylyl cyclase and subsequent elevation of cAMP. Protein kinase A is then stimulated, leading to phosphorylation of cyclic AMP response element binding protein (CREB), which alters gene expression and stimulates proliferation. The growth of SCLC is inhibited by BBR and VIPR antagonists. This review will focus on how GPCRs for VIP and BB are molecular targets for early detection and treatment of cancer.
Evolutionary origins and impacts of genome architecture in ciliates
Authors: Maurer‐Alcalá Xyrus X. , Nowacki Mariusz
Published: May 2019

Genome architecture is well diversified among eukaryotes in terms of size and content, with many being radically shaped by ancient and ongoing genome conflicts with transposable elements (e.g., the large transposon‐rich genomes common among plants). In ciliates, a group of microbial eukaryotes with distinct somatic and germ‐line genomes present in a single cell, the consequences of these genome conflicts are most apparent in their developmentally programmed genome rearrangements. This complicated developmental phenomenon has largely overshadowed and outpaced our understanding of how germ‐line and somatic genome architectures have influenced the evolutionary dynamism and potential in these taxa. In our review, we highlight three central concepts: how the evolution of atypical ciliate germ‐line genome architectures is linked to ancient genome conflicts; how the complex, epigenetically guided transformation of germline to soma during development can generate widespread genetic variation; and how these features, coupled with their unusual life cycle, have increased the rate of molecular evolution linked to genome architecture in these taxa.
Influence of the regulatory peptide galanin on cytokine expression in human monocytes
Authors: Ramspacher Andrea , Neudert Magdalena , Koller Andreas , Schlager Sandra , Kofler Barbara , Brunner Susanne Maria
Published: May 2019

Current research into neuropeptides is bringing to light many remarkable functions of these endocrine/neurocrine/paracrine factors, such as their roles in modulating immune responses. Galanin is a neuropeptide expressed in both neural and non‐neural tissues and exerts its effects through three G protein–coupled receptors, GAL1,2,3‐R. It has been demonstrated that galanin has modulatory effects on immune cells, including neutrophils and natural killer cells. Because monocytes express GAL2‐R, and therefore are expected to be a target of galanin, we analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Galanin increased the expression of IL‐1β up to 1.5‐fold, TNF‐α, IL‐10, IL‐18, and CCL3 up to twofold, and CXCL8 up to fourfold in nonactivated monocytes, but had no major effect on activated monocytes. A cross‐correlation analysis of cytokine expression profiles, irrespective of the activation status of the monocytes, revealed that galanin changed the cross‐correlation of the expression of certain cytokines. Galanin abolished several significant correlations in IFN‐γ–stimulated monocytes. For example, treatment with 10 nM galanin changed the Spearman's rank coefficient of IL‐18 and CXCL8 from 0.622 (P ≤ 0.01) to 0.126. These results further emphasize the importance of neuroregulatory peptides, such as galanin and their therapeutic potential to treat inflammatory diseases.
Identification of biomarkers indicative of functional skeletal stem cells
Authors: Qiryaqoz Zeena , Timilsina Suraj , Czarnowski Daniel , Krebsbach Paul H. , Villa‐Diaz Luis G.
Published: May 2019

Structured Abstract

Objectives

Skeletal stem cells (SSCs) are characterized by expression of cell surface biomarkers and their ability to differentiate into bone, cartilage and fat. However, the current biomarkers used to identify these cell populations are not cell‐type‐specific or indicative of the differentiation status of these cells and are therefore unreliable. Our objective was to identify alternative cell surface biomarkers and transcription factors shared between SSCs isolated from the bone marrow (BM) and those derived from pluripotent stem cells (PSC).

Materials and Methods

Human PSCs were induced into SSCs. FACS and qRT‐PCR were used to determine differences in expression of cell surface biomarkers and transcription factors between SSCs derived from PSCs and isolated from BM, in differentiating cells, in cells from early and late passage, and in fibroblasts.

Results

A significant reduction in proliferation and capacity of SSCs to differentiate into adipocytes and osteoblasts was observed after 3 passages. Protein and mRNA analysis indicated that commonly used biomarkers remain highly expressed in cells that lost capacity for differentiation. However, integrin α6 (CD49f) and transcription factors GATA6, PRDM16, SIM2 and SOX11 were significantly upregulated in SSCs compared to fibroblasts. In early stages of adipogenic and osteogenic differentiation, the expression of CD49f, GATA6 and SIM2 was reduced in later passage cells, which have limited proliferation and differentiation capabilities.

Conclusions

Our results suggest that CD49f and transcription factors GATA6 and SIM2 identify functional SSCs.
Mechanobiology of bone and suture – Results from a pig model
Authors: Rafferty Katherine L. , Baldwin Michael C. , Soh Shean Han , Herring Susan W.
Published: May 2019

Structured Abstract

Objective

To compare the morphology and mechanical function of sutures in normal pigs and minipigs to those of Yucatan minipigs, a natural model for midfacial hypoplasia.

Setting and Sample Population

Research took place at the Department of Orthodontics at the University of Washington and used varying sample sizes of normal‐snouted pigs and Yucatan minipigs.

Material and Methods

Skulls and heads were examined for morphology of the nasofrontal suture using computed tomography and histology. Strain gauge recordings were made of sutural strain during mastication and during cyclic tensile loading of the nasofrontal suture.

Results

Sutures in Yucatans had narrower gaps than same‐age normal pigs. The nasofrontal suture was simpler in construction and had more active osteoblasts on the bone fronts in Yucatans. The sutural ligament was less well organized, and based on a small sample, masticatory strain appeared to be lower than in normal minipigs. However, sutures were not fused and showed similar strains in response to the cyclic loading procedure.

Conclusion

Midfacial hypoplasia in Yucatan pigs has the likely proximate cause of hyperossification. Yet prior to fusion, the sutures appear to be amenable to treatment that would promote their growth rate.
3D superimposition of craniofacial imaging—The utility of multicentre collaborations
Authors: Yatabe Marilia , Prieto Juan Carlos , Styner Martin , Zhu Hongtu , Ruellas Antonio Carlos , Paniagua Beatriz , Budin Francois , Benavides Erika , Shoukri Brandon , Michoud Loic , Ribera Nina , Cevidanes Lucia
Published: May 2019

Structured Abstract

Clinical applications of 3D image registration and superimposition have contributed to better understanding growth changes and clinical outcomes. The use of 3D dental and craniofacial imaging in dentistry requires validate image analysis methods for improved diagnosis, treatment planning, navigation and assessment of treatment response. Volumetric 3D images, such as cone‐beam computed tomography, can now be superimposed by voxels, surfaces or landmarks. Regardless of the image modality or the software tools, the concepts of regions or points of reference affect all quantitative of qualitative assessments. This study reviews current state of the art in 3D image analysis including 3D superimpositions relative to the cranial base and different regional superimpositions, the development of open source and commercial tools for 3D analysis, how this technology has increased clinical research collaborations from centres all around the globe, some insight on how to incorporate artificial intelligence for big data analysis and progress towards personalized orthodontics.
Osteocytes and mechanical loading: The Wnt connection
Authors: Bullock Whitney A. , Pavalko Frederick M. , Robling Alexander G.
Published: May 2019

Structured Abstract

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility.
Extracellular vesicle identification in tooth movement models
Authors: Holliday L. Shannon , Truzman Estella , Zuo Jian , Han Guanghong , Torres‐Medina Rosemarie , Rody Wellington J.
Published: May 2019

Structured Abstract

Extracellular vesicles (EVs) are 30‐150 nm in diameter vesicles released by cells that serve important intercellular regulatory functions. EVs include exosomes and microvesicles. Exosomes form in multivesicular bodies and are released extracellularly as the multivesicular bodies fuse with the plasma membrane. Microvesicles bud directly from the plasma membrane. Here, we examine methods that are available or emerging to detect and study EVs during orthodontic tooth movement (OTM). EV's involvement in regulating bone remodelling associated with OTM may be demonstrated by adding isolated EVs to an animal model to change the rate of tooth movement. Exosomes in multivesicular bodies might be detected by immunogold labelling of markers in sections from the tooth and jaw and detection by electron microscopy. Gingival crevicular fluid (GCF) is enriched in EVs. Detection and characterization of EVs released by osteoclasts during resorption have been described, and this information could be used to analyse EVs in OTM models. Regulatory EVs may be enriched in the GCF from teeth that are being moved or are undergoing root resorption. Emerging approaches, including nanoparticle tracking, ExoView and micro‐ and nanofluidics, show promise for studying EVs in the GCF. Techniques that amplify signal, including polymerase chain reaction (PCR), provide the sensitivity necessary to utilize EVs from GCF as biomarkers. Studies of the role of EVs in OTM will provide fresh insight that may identify means for enhancing OTM procedures. EVs in GCF may include biomarkers for bone remodelling during OTM, orthodontic‐associated root resorption, and other dental pathologies.
Locating and Representing Pain
Authors: Gozzano Simone
Published: May 2019

Two views on the nature and location of pain are usually contrasted. According to the first, experientialism, pain is essentially an experience, and its bodily location is illusory. According to the second, perceptualism or representationalism, pain is a perceptual or representational state, and its location is to be traced to the part of the body in which pain is felt. Against this second view, the cases of phantom, referred and chronic pain have been marshalled: all these cases apparently show that one can be in pain while not having anything wrong in her body. Pain bodily location, then, would be illusory. I this paper I shall defend the representational thesis by presenting an argument against experientialism while conceding that the appearance/reality distinction collapses. A crucial role in such identification is played by deictics. In reporting that we feel pain here, the deictic directly refers to the bodily part as coinciding with the part as represented. So, pain location is not illusory. The upshot is that the body location is part and parcel of the representational content of pain states, a representation build up from the body map.
Tracing the Boundaries of Motivated Reasoning: How Deliberative Minipublics Can Improve Voter Knowledge
Authors: Már Kristinn , Gastil John
Published: May 2019

A large body of work shows that reasoning motivated by partisan cues and prior attitudes leads to unreflective decisions and disparities in empirical beliefs across groups. Surprisingly little research, however, has tested the limits of motivated reasoning. We argue that the publicly circulated findings of deliberative minipublics can spark a more reflective motivation in voters when these bodies provide policy‐relevant factual information. To test that proposition, we conducted a survey experiment using information generated by one such minipublic during an election. Results showed that exposure to the minipublic's findings improved the accuracy of voters' empirical beliefs regarding a ballot proposition on the regulation of genetically modified seeds. This treatment effect transcended voters' partisan identities and prior environmental attitudes. In some instances, the respondents showing the greatest knowledge gains were those who a directional motivated‐reasoning account would have expected to resist the treatment most effectively, owing to party identity or prior attitudes.
Exercise‐based cardiac rehabilitation is associated with a normalization of the heart rate performance curve deflection
Authors: Heber Stefan , Sallaberger‐Lehner Marina , Hausharter Maria , Volf Ivo , Ocenasek Helmuth , Gabriel Harald , Pokan Rochus
Published: May 2019

The heart rate (HR) rises with increased power output, whereby in most healthy individuals, the slope of HR levels off with higher intensity. This corresponds to a downward deflection of the heart rate performance curve (HRPC). Conversely, in patients after myocardial infarction, an upward HRPC deflection is frequently observed that is especially pronounced in patients with compromised left ventricular ejection fraction. To investigate whether regular endurance training during cardiac rehabilitation might normalize HRPC, data of 128 male patients were analyzed. All patients performed three exercise tests: at baseline, after 6 weeks, and after 1 year. Ninety‐six patients exercised regularly according to guidelines for 1 year (training group, TG), and 32 stopped after 6 weeks (control group, CG). Similarly, upward‐deflected HRPCs were observed at baseline and after 6 weeks in both groups. After 1 year, TG patients had less upward‐deflected HRPCs compared with CG ones, corresponding to a partial normalization. Greater changes in HRPC deflection were associated with larger improvements in cardiorespiratory fitness. Our results might indicate improved myocardial function due to long‐term rehabilitation. Further, HRPC alterations over time should be considered when prescribing exercise intensities using a target HR, as deflection flattening might render the intensity of corresponding exercise insufficient.
The identification of a novel HLA‐B allele, HLA‐B*27:05:38
Authors: Gareau Alison J. , Mostafa Ahmed A. , Stamm Luz , Khan Faisal , Berka Noureddine
Published: May 2019

HLA‐B*27:05:38 differs from HLA‐B*27:05:02:01 by 2 mismatches in exon 3, resulting in 2 synonymous mutations.
Challenges in an X + Y ambulatory model
Authors: Ibrahim Walid , Adam Omeralfaroug , Mohamed Abdelaziz , Subahi Ahmed , Osman Lubna , Hassan Abubaker AI , Yassin Ahmed S , Thati Neelima , Weinberger Jarrett , Levine Diane
Published: May 2019

Background

Internal medicine training requires significant exposure to ambulatory practice. Ensuring continuity of patient care is challenging, especially with intermittent ambulatory resident assignments. A popular scheduling model is an X + Y block system where residents rotate for X weeks on inpatient rotations followed by Y weeks on ambulatory clinics. Although benefits exist with the X + Y model, it has drawbacks, particularly for continuity of care: residents struggle to obtain follow‐up test results and return patient calls promptly. To provide patients with seamless continuity the programme assigned two Managing Clinic Continuity Care Residents (MCCCRs) to cover all tasks. The MCCCRs were soon overwhelmed by the number of tasks and became dissatisfied with the workflow, however, resulting in a low task‐completion rate.

Method

In our 4 + 1 model residents are divided into five cohorts, we created mini‐practice groups (MPGs) consisting of one resident from each cohort. Each week the resident in the clinic is assigned to act as the Practice Clinic Continuity of Care Resident (PCCCR) for the MPG. This individual is responsible for addressing the patient tasks of the other four residents in the MPG. For optimal performance, the previous two MCCCRs are now assigned for oversight only each week. We tracked task‐completion rates weekly and surveyed residents for satisfaction.

Results

Following the redistribution of responsibilities, the task‐completion rates improved from 75 to 97%. The MCCCR satisfaction rate for the workflow increased from zero to 63%, and the on‐time note completion rates increased from 21 to 67%.

Conclusion

Modification of the X + Y model using the MPG structure ensured the timely completion of patient‐related tasks, and improved the overall experience for both patients and providers.

Modification of the X + Y model using the MPG structure ensured the timely completion of patient‐related tasks, and improved the overall experience for both patients and providers
Robust abnormality detection methods for spatial search of radioactive materials
Authors: Jeong Myeong‐Hun , Sullivan Clair J. , Gao Yizhao , Wang Shaowen
Published: May 2019

Radiological dirty bombs and improvised nuclear devices pose a significant threat to both public health and national security. Growing networks of radiation sensors have been deployed by a number of offices within the U.S. and international agencies. Detecting such threats while minimizing false alarm rates presents a considerable challenge to homeland security and public health. This research aims to achieve a higher probability of detection with a lower probability of false alarms. It focuses on the local spatial instability of radiation levels in order to detect radioactive materials based on robust outlier detection methods. Our approach includes a three‐step abnormality detection method consisting of one‐dimensional robust outlier detection for all gamma‐ray counts, a density‐based clustering analysis, and a two‐dimensional robust outlier detection method using a bagplot, based on spatial associations. The effectiveness of the method proposed is demonstrated through a case study, wherein radioactive materials are detected in urban environments, and its performance is compared with alternative methods employing ak‐sigma approach, local Getis–Ord () statistic, and the goodness of fit of the Poisson distribution.
GIS&T pedagogies and instructional challenges in higher education: A survey of educators
Authors: Mathews Adam J. , Wikle Thomas A.
Published: May 2019

Anyone involved in teaching the principles and applications of geographic information science and technology (GIS&T) understands the challenges of effective instruction within an environment subject to nearly constant change. Indeed, the dynamic nature of GIS&T introduces both new paradigms and increasingly powerful tools for exploring spatial relationships. However, while past efforts among educators and practitioners have identified knowledge and competencies important to GIS&T learning, less attention has been directed at methods used to teach GIS&T. For example, while some instructors employ traditional approaches such as lectures and structured laboratory exercises, others have shifted to active learning strategies such as “flipped classrooms” and collaborative, project‐oriented assignments. In this article, we assess the pedagogical approaches used to teach GIS&T courses through an Internet‐based survey of 318 college and university faculty. Our findings demonstrate that active learning pedagogies are becoming more firmly established, supplementing or replacing traditional teaching approaches. Contrary to our assumptions, age and teaching experience are not factors that influence the adoption of active learning strategies. Along with assessing instructional approaches, our survey identifies the challenges associated with teaching GIS&T, as identified by survey respondents.
A comparison of lancets and evaluation of various manoeuvres in reducing finger prick pain during pre‐donation haemoglobin estimation
Authors: Dubey A. , Sonker A. , Agarwal P.
Published: May 2019

Objectives

Three different types of lancets have been compared to identify and implement the one that causes the least pain. Simple manoeuvres during the lancing procedure have been evaluated to determine their effectiveness in reducing the intensity of perceived pain.

Background

Pre‐donation haemoglobin estimation is performed by pricking the donor's finger with a lancet. Pain associated with the procedure causes fear and anxiety, which dissuades the donors from donating blood.

Methods

In 100 subjects, finger prick was performed using three different lancets, and the subjects were asked to score their pain on a numerical rating scale (NRS). A further 150 blood donors were subjected to routine finger pricking for Hb estimation and were asked to score their pain on an NRS. After 15 min, they underwent a second prick with application of a manoeuvre (breath holding, coughing trick or looking away) and again marked their pain scores on the NRS.

Results

Participants reported the least pain scores with lancing devices that have a spring mechanism to retract the lancets soon after penetration into the skin. Breath holding and the cough trick manoeuvre reduced the perceived pain scores significantly.

Conclusion

Lancing devices merit consideration for routine use, and a simple manoeuvre may be applied to reduce perceived pain.
Red blood cells donated by smokers: A pilot investigation of recipient transfusion outcomes
Authors: DeSimone Robert A. , Hayden Joshua A. , Mazur Chase A. , Vasovic Ljiljana V. , Sachais Bruce S. , Zhao Zhen , Goel Ruchika , Hsu Yen‐Michael S. , Racine‐Brzostek Sabrina E. , Cushing Melissa M.
Published: May 2019

BACKGROUND

Current regulations do not require blood collection facilities to ask donors about cigarette smoking, and the prevalence of nicotine and its metabolites in blood products is not well established. Although smokers have higher hemoglobin (Hb) levels, smoking may adversely affect the quality of donated red blood cells through higher carboxyhemoglobin (COHb) content and premature hemolysis.

STUDY DESIGN AND METHODS

Red blood cell (RBC) unit segments from 100 unique donors were tested for nicotine and its metabolite cotinine by mass spectrometry and for COHb spectrophotometrically. Outcomes were evaluated retrospectively in adult non‐bleeding patients receiving single RBC units.

RESULTS

Thirteen of 100 RBC segments (13%) were positive for cotinine at levels consistent with current smoking (> 10 ng/mL). The cotinine positive RBCs showed significantly greater COHb content compared to cotinine negative units (median 3.0% vs. 0.8%, p = 0.007). For patients transfused cotinine‐positive units, there was no significant change in their vital signs following transfusion and no transfusion reactions were observed. However, patients transfused cotinine‐positive units showed significantly reduced hematocrit and hemoglobin increments (median +1.2% and +0.4 g/dL) following transfusion compared to patients receiving cotinine negative units (median +3.6% and +1.4 g/dL) (p = 0.014).

CONCLUSION

Thirteen percent of RBC units tested positive for cotinine at levels consistent with active smoking, accordant with the estimated national smoking rate of 15.5%. Cotinine‐positive RBC units had greater COHb content and showed reduced hematocrit and hemoglobin increments following transfusion. These preliminary results should be validated in a larger cohort.
Enhancement of mouse diaphragm contractility in the presence of antagonists of GABAA and GABAB receptors
Authors: Lenina Oksana , Petrov Konstantin , Kovyazina Irina , Malomouzh Artem
Published: May 2019

New Findings

What is the central question of this study?

Do GABA receptors play any role at the neuromuscular junction?

What is the main finding and its importance?

In the presence of either ionotropic or metabotropic GABA receptor antagonists, diaphragm muscle force production elicited by stimulating the motor nerve at ≥50 Hz was increased. Our data indicate the presence of GABAergic signalling at the neuromuscular junction.

Despite the signalling role of GABA in the brain and spinal cord, the role of this molecule in the peripheral nervous system and, in particular, at the neuromuscular junction remains practically unexplored. In the present work, the force of mouse diaphragm contractions was measured in the presence of blockers of metabotropic GABAB receptors (CGP 55845) and ionotropic GABAA receptors (picrotoxin) with various patterns of indirect and direct stimulation of muscle by trains of 40 pulses delivered at 10, 20, 50 and 70 Hz. It was found that neither blocker affected the diaphragm contractility caused by indirect stimulation through the motor nerve at 10 and 20 Hz. However, when the stimulation frequency was increased to 50 or 70 Hz, the force of subsequent contractions in the train (when compared with the amplitude of contraction in response to the first pulse) was increased by both CGP 55845 and picrotoxin. With direct stimulation of the diaphragm, no significant changes in the contraction force were detected at any frequency used. The results obtained support the following conclusions: (i) pharmacological inhibition of GABA receptors increases the contractile activity of skeletal muscle; and (ii) frequency‐dependent enhancement of GABA receptor activation takes place in the region of the neuromuscular junction.
Benchmark Investigation of Welding-Induced Buckling and Its Critical Condition During Thin Plate Butt Welding
Authors: Wang Jiangchao , Yi Bin
Published: May 2019

Welding-induced buckling is a special type of welding distortion occurring during thin plate butt welding and was investigated using both experimental and computational approaches for this benchmark investigation. In addition, the characteristic parameter and its magnitude for the occurrence of welding-induced buckling were also presented. Fundamental theories of the inherent deformation, finite strains, and eigenvalues of the structure stiffness matrix were considered to investigate welding-induced buckling. A series of experiments on thin plate butt welding with different heat inputs were conducted, and buckling behavior was observed from the deformed shape and the distribution of out-of-plane welding distortion. Transient nonlinear thermal elastic–plastic finite element (TEP FE) and elastic finite element (FE) analyses were conducted to predict welding-induced buckling, and the results were in good agreement with the measurement data. Criteria for the occurrence of welding-induced buckling were proposed and discussed. Inherent deformation was considered as a characteristic parameter of buckling behavior during welding, and its critical magnitude was calculated using a loading incremental method and eigenvalue analysis with good agreement.