bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of fibrinogen carbamylation on fibrin clot formation and stability
Authors: Jaisson Stéphane , Gillery Philippe , Scavenius Carsten , Spriet Endy , Nyhaug Anne , Roberts Helen , Chapple Iain , Hellvard Annelie , Delaleu Nicolas , Mydel Piotr , Binder Veronika , Bergum Brith
Published: April 2017

Carbamylation is a non-enzymatic post-translational modification induced upon exposure of free amino groups to urea-derived cyanate leading to irreversible changes of protein charge, structure and function. Levels of carbamylated proteins increase significantly in chronic kidney disease and carbamylated albumin is considered as an important biomarker indicating mortality risk. High plasma concentrations and long half-life make fibrinogen a prime target for carbamylation. As aggregation and cross-linking of fibrin monomers rely on lysine residues, it is likely that carbamylation impacts fibrinogen processing. In this study we investigated carbamylation levels of fibrinogen from kidney disease patients as well as the impact of carbamylation on fibrinogen cleavage by thrombin, fibrin polymerisation and cross-linking in vitro. In conjunction, all these factors determine clot structure and stability and thus control biochemical and mechanical properties. LC-MS/MS analyses revealed significantly higher homocitrulline levels in patient fibrinogen than in fibrinogen isolated from control plasma. In our in vitro studies we found that although carbamylation does not affect thrombin cleavage per se, it alters fibrin polymerisation kinetics and impairs cross-linking and clot degradation. In addition, carbamylated fibrin clots had reduced fiber size and porosity associated with decreased mechanical stability. Using mass spectroscopy, we discovered that N-terminally carbamylated fibrinopeptide A was generated in this process and acted as a strong neutrophil chemoattractant potentially mediating recruitment of inflammatory cells to sites of fibrin(ogen) turnover. Taken together, carbamylation of fibrinogen seems to play a role in aberrant fibrin clot formation and might be involved in haemostatic disorders associated with chronic inflammatory diseases.
On-clopidogrel platelet reactivity as predictor for long-term clinical outcome in patients after planned discontinuation of clopidogrel
Authors: Bömicke Timo , Valina Christian , Stratz Christian , Amann Michael , Neumann Franz-Josef , Hochholzer Willibald
Published: April 2017

It is unknown whether the known association of high on-treatment platelet reactivity (HTPR) with worse clinical outcome in patients on clopidogrel following coronary stent implantation persists after planned discontinuation of clopidogrel. This study investigated the association of HTPR with major ischaemic events after planned discontinuation of clopidogrel. Consecutive patients undergoing elective coronary stent implantation after loading with clopidogrel 600 mg were followed for up to seven years (n=765). Platelet reactivity was tested on day 1 after coronary intervention. Clopidogrel was continued for six months after implantation of drug-eluting stents and for one month if only bare-metal stents were used. The combined primary endpoint was death of any cause or non-fatal myocardial infarction (MACE). HTPR was found in 217 of 765 patients (28%). During a median follow-up of 5.7 years, the primary endpoint occurred in 145 subjects after planned discontinuation of clopidogrel. Patients with HTPR showed a higher incidence of MACE after discontinuation of clopidogrel. There was a significant interaction of HTPR and time following discontinuation of clopidogrel beyond one year (p for interaction 0.08). Landmark analyses confirmed that the association of HTPR and MACE was only significant within the first year (HR: 2.93, 95%-CI 1.13–7.60, p=0.03), but not beyond the first year following discontinuation of clopidogrel (HR: 1.19, 95%-CI 0.82–1.72, p=0.37). In conclusion, patients with HTPR persist to be at high risk for death or myocardial infarction even following planned discontinuation of clopidogrel. However, this association was only significant for the first year following discontinuation of clopidogrel.
Textural Composition: Aesthetics, Techniques, and Spatialization for High-Density Loudspeaker Arrays
Authors: Hagan Kerry L.
Published: April 2017

This article documents a personal journey of compositional practice that led to the necessity for working with high-density loudspeaker arrays (HDLAs). I work with textural composition, an approach to composing real-time computer music arising from acousmatic and stochastic principles in the form of a sound metaobject. Textural composition depends upon highly mobile sounds without the need for trajectory-based spatialization procedures. In this regard, textural composition is an intermediary aesthetic—between “tape music” and real-time computer music, between sound objects and soundscape, and between point-source and trajectory-based, mimetic spatialization.

I begin with the aesthetics of textural composition, including the musical and sonic spaces it needs to inhabit. I then detail the techniques I use to create textures for this purpose. I follow with the spatialization technique I devised that supports the aesthetic requirements. Finally, I finish with an example of an exception to my techniques, one where computational requirements and the HDLA required me to create a textural composition without my real-time strategies.
Introduction: How Should We Study International Criminal Law? Reflections on the Potentialities and Pitfalls of Interdisciplinary Scholarship
Authors: Burgis-Kasthala Michelle Leanne
Published: April 2017

This introduction explores interdisciplinarity by first considering law as a discipline to account for how international criminal law has emerged as a field of practice and scholarship within the broader epistemic context of law. It then considers the nature of international criminal law scholarship before turning to questions of interdisciplinarity.
The Tower of Babel and Yahweh’s Heavenly Staircase
Authors: Michael Matthew
Published: April 2017

The people of ancient societies and modern times have continually had an unusual fascination for tall structures. In the Hebrew Bible, however, gigantic structures rarely feature in the plotting of its stories. In contrast to this literary norm, the narrator of Genesis places two elevated structures at the center of his story, namely the tower of Babel (Gen 11) and the heavenly staircase at Bethel (Gen 28). In these two locations, the narrator appears to have situated the two structures above all the characters and the architectural landmarks of Genesis. Consequently, the paper engages the theological elevation of these two high-level spots in the creative mapping of Genesis’ subtle representations of human-divine tensions. While past studies have diachronically described the individual significance of these two vertical representations in Genesis, the present paper underscores the intertextual/theological importance of these two elevated structures in the narrative space of Genesis.
Two new Neotropical species of Djalmabatista Fittkau (Diptera: Chironomidae)
Authors: DANTAS GALILEU P. S. , HAMADA NEUSA
Published: April 2017

Two new species of Djalmabatista from northern Brazil are described and illustrated, Djalmabatista patamona sp. nov. based on adult male and pupa and Djalmabatista wapixana sp. nov. based on adult male only.
Reduced-Order Modeling of Stratospheric Winds and Its Application in High-Altitude Balloon Trajectory Simulations
Authors: Ramesh Sai Sudha , Lim Kian Meng , Lee Heow Pueh , Khoo Boo Cheong
Published: April 2017

The knowledge of weather conditions at the stratosphere is important for the planning and execution of high-altitude balloon flights, which require an accurate modeling of weather data over a period of time. Various methods based on statistical analysis, artificial neural networks, and cluster analysis have been employed to model the temporal variation of weather parameters. In the present study, a proper orthogonal decomposition (POD) method has been used to study the spatial as well as temporal variations of wind data in Singapore. The use of POD facilitates a compact representation of the weather dataset and aids in faster computation of wind profiles for use in balloon trajectory simulation. Further, the results reveal the existence of the quasi-biennial oscillation phenomenon, which is characteristic of equatorial easterly–westerly winds. This phenomenon enables the development of a Fourier prediction model, which can be used in real-time balloon trajectory simulations. The Fourier model is observed to be sensitive to wind velocity fluctuations, especially in the vicinity of alternating wind directions. However, it provides a reasonable projection of balloon trajectory, which can be used in preliminary planning and testing of high-altitude flights. Thus, a prior knowledge of wind profiles based on POD or a Fourier model aids in balloon station keeping. A simple case of altitude-controlled balloon flight is presented, and the results highlight the advantages of the present method in balloon station keeping.
Statistics and Meteorology of Air Pollution Episodes over the South African Highveld Based on Satellite–Model Datasets
Authors: Jury Mark R.
Published: April 2017

The meteorological conditions associated with air pollution episodes on South Africa’s Highveld were studied using Ozone Monitoring Instrument (OMI) and Atmospheric Infrared Sounder (AIRS) satellite estimates, MERRA2 reanalysis model products, and in situ weather data. Surface-layer sulfur dioxide (SO2) and nitrogen dioxide (NO2) display high concentrations during winter (May–July) and provide a focus for statistical analysis of monthly and daily time series. Highveld area-averaged monthly model SO2 was temporally correlated with boundary layer height (correlation coefficient of −0.76) and temperature lapse rate (+0.65) for the period of 1980–2015, but relationships with winds were weak. Daily Highveld area-averaged satellite NO2 was related to dewpoint temperature (−0.59) and exhibited pulsing in the range of 7–24 days for 2005–15. High concentrations of these short-lived locally generated air pollutants were found over and southeast of Johannesburg as a result of urban and industrial emissions. The spatial regression of daily NO2 onto regional sea level air pressure fields for May–July over 2005–15 revealed the slow eastward movement of an anticyclone. At the climatic time scale, Pacific Ocean La Niña conditions favored an increase of May–July SO2 concentrations when sea surface temperatures in the equatorial Atlantic Ocean were warmer than normal. The meteorological pattern underlying the highest-ranked air pollution event of 18–25 July 2008 was characterized by sharp anticyclonic curvature of low-level winds that induce subsidence and consequently a stable lapse rate and low dewpoint temperature (−5°C). The wind vorticity exerted a stronger influence on dispersion than did the surface divergence. This new understanding will underpin better air-quality forecasts over the South African Highveld.
Potential Predictability during a Madden–Julian Oscillation Event
Authors: Jones Charles , Dudhia Jimy
Published: April 2017

The Madden–Julian oscillation (MJO) is an important source of predictability. The boreal 2004/05 winter is used as a case study to conduct predictability experiments with the Weather Research and Forecasting (WRF) Model. That winter season was characterized by an MJO event, weak El Niño, strong North Atlantic Oscillation, and extremely wet conditions over the contiguous United States (CONUS). The issues investigated are as follows: 1) growth of forecast errors in the tropics relative to the extratropics, 2) propagation of forecast errors from the tropics to the extratropics, 3) forecast error growth on spatial scales associated with MJO and non-MJO variability, and 4) the relative importance of MJO and non-MJO tropical variability on predictability of precipitation over CONUS.

Root-mean-square errors in forecasts of normalized eddy kinetic energy (NEKE) (200 hPa) show that errors in initial conditions in the tropics grow faster than in the extratropics. Potential predictability extends out to about 4 days in the tropics and 9 days in the extratropics. Forecast errors in the tropics quickly propagate to the extratropics, as demonstrated by experiments in which initial conditions are only perturbed in the tropics. Forecast errors in NEKE (200 hPa) on scales related to the MJO grow slower than in non-MJO variability over localized areas in the tropics and short lead times. Potential predictability of precipitation extends to 1–5 days over most of CONUS but to longer leads (7–12 days) over regions with orographic precipitation in California. Errors in initial conditions on small scales relative to the MJO quickly grow, propagate to the extratropics, and degrade forecast skill of precipitation.
Sensitivities of 1-km Forecasts of 24 May 2011 Tornadic Supercells to Microphysics Parameterizations
Authors: Stratman Derek R. , Brewster Keith A.
Published: April 2017

On 24 May 2011, Oklahoma experienced an outbreak of tornadoes, including one rated EF5 on the enhanced Fujita (EF) scale and two rated EF4. The extensive observation network in this area makes this an ideal case to examine the impact of using five different microphysics parameterization schemes, including single-, double-, and triple-moment microphysics, in an efficient high-resolution data assimilation system suitable for nowcasting and short-term forecasting with low latencies. Additionally, the real-time configuration of the 1-km ARPS, which assimilated increments produced by 3DVAR with cloud analysis using incremental analysis updating (IAU), had success providing a good baseline forecast. ARPS forecasts of 0–2 h are verified using observation-point, neighborhood, and object-based verification techniques. The object-based verification technique uses updraft helicity fields to represent mesocyclone centers, which are verified against tornado locations from three supercells of interest. Varying levels of success in the forecasts are found and appear to be dependent on the complexity of the storm interaction, with early forecasts of isolated storms exhibiting the most success. Verification scores indicate that the multimoment microphysics schemes tend to produce better forecasts of tornadic supercells. However, some of the forecasts from the single-moment microphysics schemes perform as well as or better than the forecasts from the multimoment microphysics schemes.
Career Implications of Having a Female-Friendly Supervisor
Authors: Bednar Steven , Gicheva Dora
Published: April 2017

The authors study how variations in supervisors’ attitudes toward working with females generate gender differences in workers’ observed career outcomes. The employment records of athletic directors and head coaches in a set of NCAA Division I programs provide longitudinal matched employer–worker data. Supervisors are observed at multiple establishments, which allows the authors to construct a measure of revealed type and to examine its role for the performance and turnover of lower-level employees. The authors observe that the careers of male and female workers progress differently depending on supervisor type in a way that is consistent with a type-based mentoring model. The results suggest that more focus should be placed on managerial attitudes revealed through actions in addition to observable attributes such as gender.
Effects of needle-punched nonwoven structure on the properties of sandwich flexible composites under static loading and low-velocity impact
Authors: Yan Ruosi , Huang Shih-Yu , Huang Chen-Hung , Hsieh Chien-Teng , Lou Ching-Wen , Lin Jia-Horng
Published: April 2017

The current study fabricated nylon/high-resilience bonding polyester (HRPET) nonwoven fabric with various needle-punching parameters and investigated the effect of these variations on the response of high-density flexible foam under static loading and low-velocity impact. The needle-punching depth and frequency are selected as variations. The HRPET fiber generates bonding-points when being thermally treated, which provides resilience properties on the sandwich flexible composites. The results find a substantial relationship between the temperature of thermal treatment and the absorption of low-velocity impact energy which is mainly because of the increase of fiber connection force. The impact force is eliminated by 8255 N at most. Needle-punching depth contributes to resistance to static loading and the highest resistance was 2043 N.
Accelerating Innovation in the Creation of Biovalue
Authors: Gardner John , Webster Andrew
Published: April 2017

The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to “accelerate” innovation. This article examines in detail one such agency, the United Kingdom’s Cell and Gene Therapy Catapult (CGTC). We describe CGTC’s role as an accelerator agency and its value narrative, which combines both “health and wealth.” Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field.
Elucidating and Modulating the Neural Correlates of Visuospatial Working Memory via Noninvasive Brain Stimulation
Authors: Juan Chi-Hung , Tseng Philip , Hsu Tzu-Yu
Published: April 2017

Visuospatial working memory refers to the short-term memory mechanism that enables humans to remember visual information across visual blackout periods such as eyeblinks or eye movements. In recent years, neuroscientific studies have made great progress in uncovering the brain regions that support visuospatial working memory. In this review, we focus on the role of the posterior parietal cortex in forming and maintaining visual information, and use it as an example to highlight how noninvasive brain-stimulation techniques, particularly transcranial magnetic, direct current, and alternating current stimulation, can shed light on this topic because of their unique strengths in modulating brain activities.
On the Origins of Phonology
Authors: Berent Iris
Published: April 2017

Why do humans drink and drive but fail to rdink and rdive? Here, I suggest that these regularities could reflect abstract phonological principles that are active in the minds and brains of all speakers. In support of this hypothesis, I show that (a) people converge on the same phonological preferences (e.g., dra over rda) even when the relevant structures (e.g., dra, rda) are unattested in their language and that (b) such behavior is inexplicable by purely sensorimotor pressures or experience with similar syllables. Further support for the distinction between phonology and the sensorimotor system is presented by their dissociation in dyslexia, on the one hand, and the transfer of phonological knowledge from speech to sign, on the other. A detailed analysis of the phonological system can elucidate the functional architecture of the typical mind/brain and the etiology of speech and language disorders.
Where Health and Death Intersect
Authors: Arndt Jamie , Goldenberg Jamie L.
Published: April 2017

This article offers an integrative understanding of the intersection between health and death from the perspective of the terror management health model. After highlighting the potential for health-related situations to elicit concerns about mortality, we turn to the question, how do thoughts of death influence health-related decision making? Across varied health domains, the answer depends on whether these cognitions are in conscious awareness or not. When mortality concerns are conscious, people form healthy intentions and engage in healthy behavior if efficacy and coping resources are present. In contrast, when contending with accessible but nonconscious thoughts of death, health-relevant decisions are guided more by the implications of the behavior for the individual’s sense of cultural value. Finally, we present research suggesting how these processes can be leveraged to facilitate health promotion and reduce health risk
Competitive Selection and Age-Related Changes in Visual Attention
Authors: McCarley Jason S. , Mounts Jeffrey R. W.
Published: April 2017

Healthy aging entails selective losses in visual attention, including the ability to filter clutter, divide attention between inputs, and search for configurations or conjunctions of features. A model of attention as a competition to influence neurons in the visual brain provides a framework for understanding these effects. Under the model, competition is necessary to disambiguate neural responses and resolve object details when multiple stimuli fall within the same visual receptive fields. A pattern of perceptual interference between attended stimuli in close spatial proximity with one another appears to be a psychophysical marker of this competition. Studies of divided visual attention in young and older adults show pronounced age-related increases in the strength of spatial interference between attended items, but only in the presence of clutter. Results suggest that inefficient competition for selection contributes to older adults’ visual attentional difficulties, compromising the ability to resolve details of multiple stimuli within small regions of the visual field. The conceptualization of attention as a competition for selection may thus provide a framework for understanding and assessing age-related attention losses.
Triptolide inhibits the growth of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro
Authors: Jiang Chunming , Fang Xiang , Zhang Hongxu , Wang Xuepeng , Li Maoqiang , Jiang Wu , Tian Fei , Zhu Liulong , Bian Zhenyu
Published: April 2017

We aimed to study the anti-tumor effects of triptolide on osteosarcoma and the related molecular mechanisms. The cell viability, apoptosis portion, tumor size, tumor weight, and invasion of osteosarcoma cells were determined. The relative level of microRNA-181 in osteosarcoma tissues and the adjacent tissues was determined by quantitative real-time reverse transcription polymerase chain reaction. The target gene of microRNA-181a was determined and verified by luciferase report assay. At last, osteosarcoma cells were treated with triptolide and triptolide + microRNA-181a mimics to verify the relationship between triptolide and microRNA-181a. Triptolide inhibited the cell viability, promoted the apoptosis, decreased the tumor size and weight, and reduced the invasion of osteosarcoma cells. The level of microRNA-181a in osteosarcoma cells decreased significantly after treating with triptolide, and the relative level of microRNA-181a in osteosarcoma tissues was markedly higher than that in the adjacent tissues. PTEN was reported and verified the direct target gene of microRNA-181a. The overexpression of microRNA-181a decreased the inhibition of triptolide on osteosarcoma proliferation and promotion on osteosarcoma apoptosis. In conclusion, triptolide inhibited cell growth and invasion of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.
The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic biomarkers in lung adenocarcinoma
Authors: Qixing Mao , Juqing Xu , Yajing Wang , Gaochao Dong , Wenjie Xia , Run Shi , Anpeng Wang , Lin Xu , Feng Jiang , Jun Wang
Published: April 2017

Lung adenocarcinoma remains to be a high-mortality disease with few effective prognostic biomarkers. Novel biomarkers are urgently demanded to supplement the current prognostic biomarkers. Here, we explored the prognostic value of CYP3A4 and CYP3A5 in lung adenocarcinoma. The tissue microarray was made up of lung adenocarcinoma samples and corresponding normal lung tissues from Nanjing Medical University affiliated Cancer Hospital Tissue Bank. The expression of CYP3A4, together with CYP3A5, was detected by the chip data from Gene Expression Omnibus datasets and immunohistochemistry staining of the tissue microarray. Then, we assessed the relationships between CYP3A4 or CYP3A5 expression level and clinicopathological factors to estimate the clinical significance. Kaplan–Meier curves were applied to analyze the prognosis. Univariate and multivariate Cox analyses were subsequently applied to identify the independent prognostic factors. Immunohistochemistry staining results showed that by comparison with matched normal tissues, CYP3A4 was frequently hyper-expressed in lung adenocarcinoma tissues while CYP3A5 was hypo-expressed, which was consistent with the Gene Expression Omnibus analysis. Kaplan–Meier analysis indicated that high-CYP3A4 or low-CYP3A5 expression level predicted poor survival in lung adenocarcinoma patients. Multivariate Cox analysis found that hypo-expression of CYP3A5 was an independent prognostic factor. Further study revealed that combination of these two markers exhibited a more powerful predictor of poor prognosis, which could target to more accurate survival of lung adenocarcinoma. Our findings indicate that combination of CYP3A4 and CYP3A5 may serve as a novel prognostic biomarker in lung adenocarcinoma, which contribute to the precision of predicting the survival in lung adenocarcinoma.
Rat Models of Ventricular Fibrillation Following Acute Myocardial Infarction
Authors: Hundahl Laura A. , Tfelt-Hansen Jacob , Jespersen Thomas
Published: April 2017

A number of animal models have been designed in order to unravel the underlying mechanisms of acute ischemia-induced arrhythmias and to test compounds and interventions for antiarrhythmic therapy. This is important as acute myocardial infarction (AMI) continues to be the major cause of sudden cardiac death, and we are yet to discover safe and effective treatments of the lethal arrhythmias occurring in the acute setting. Animal models therefore continue to be relevant for our understanding and treatment of acute ischemic arrhythmias. This review discusses the applicability of the rat as a model for ventricular arrhythmias occurring during the acute phase of AMI. It provides a description of models developed, advantages and disadvantages of rats, as well as an overview of the most important interventions investigated and the relevance for human pathophysiology.
“No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis
Authors: Giovannoni Gavin , Tomic Davorka , Bright Jeremy R , Havrdová Eva
Published: April 2017

Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the “new normal” state of disease control for patients with MS.
Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis
Authors: Cohen Jeffrey A , Imrey Peter B , Planchon Sarah M , Bermel Robert A , Fisher Elizabeth , Fox Robert J , Bar-Or Amit , Sharp Susan L , Skaramagas Thomai T , Jagodnik Patricia , Karafa Matt , Morrison Shannon , Reese Koc Jane , Gerson Stanton L , Lazarus Hillard M
Published: April 2017

Background:

Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest.

Objective:

To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS.

Methods:

Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0–6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1–2 × 106 MSCs/kg were thawed and administered IV.

Results:

In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1–3 passages) was 1.9 × 106 MSCs/kg (range, 1.5–2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation.

Conclusion:

Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
How do international medical graduates and colleagues perceive and deal with difficulties in everyday collaboration? A qualitative study
Authors: Skjeggestad Erik , Norvoll Reidun , Sandal Gro M , Gulbrandsen Pål
Published: April 2017

Aims: Many medical doctors work outside their countries of origin. Consequently, language barriers and cultural differences may result in miscommunication and tension in the workplace, leading to poor performance and quality of treatment and affecting patient safety. However, there is little information about how foreign doctors and their colleagues perceive their collaboration and handle situations that can affect the quality of health services. Methods: Individual, semi-structured in-depth interviews were conducted with two groups of informants: 16 doctors who had recently started working in Norway and 12 unrelated Norwegian-born healthcare providers who had extensive experience of working with doctors from foreign countries. The interviews were analysed according to the systematic text condensation method. Results: The foreign doctors described themselves as newcomers and found it difficult to speak with their colleagues about their shortcomings because they wanted to be seen as competent. Their Norwegian colleagues reported that many new foreign doctors had demanding work schedules and therefore they were reluctant to give them negative feedback. They also feared that foreign doctors would react negatively to criticism. All participants, both the new foreign doctors and their colleagues, reported that they took responsibility for the prevention of misunderstandings and errors; nevertheless, they struggled to discuss such issues with each other. Conclusions: Silence was the coping strategy adopted by both the foreign doctors and native healthcare professionals when facing difficulties in their working relationships. In such situations, many foreign doctors are socialized into a new workplace in which uncertainty and shortcomings are not discussed openly. Effective leadership and procedures to facilitate communication may alleviate this area of concern.
Bee SAFE, a Skill-Building Intervention to Enhance CAM Health Literacy: Lessons Learned
Authors: Shreffler-Grant Jean , Nichols Elizabeth G. , Weinert Clarann
Published: April 2017

The purpose is to describe a feasibility study of a skill-building intervention to enhance health literacy about complementary and alternative (CAM) therapies among older rural adults and share lessons learned. A study was designed to examine the feasibility of an intervention to enhance CAM health literacy. The theme was “Bee SAFE” for Be a wise user of CAM, Safety, Amount, From where, and Effect. Modules were presented face to face and by webinar with older adults at a senior center in one small rural community. The team achieved its purpose of designing, implementing, and evaluating the intervention and assessing if it could be implemented in a rural community. The implementation challenges encountered and lessons learn are discussed. By improving CAM health literacy, older rural adults with chronic health conditions can make well-reasoned decisions about using CAM for health promotion and illness management. The goal is to implement the Bee SAFE intervention in other rural communities; thus team members were attentive to lessons to be learned before investing time, effort, and expense in the larger intervention. It is hoped that the lessons learned can be instructive to others planning projects in rural communities.
Development of a Pharmacist REferral Program in a primary cARE clinic (PREPARE): A prospective cross-sectional study
Authors: Barry Arden R.
Published: April 2017

Background:

Increasing demand for ambulatory health care services has led to the development of primary care multidisciplinary teams that include pharmacists. The objective of this study was to characterize referrals to a pharmacist in a primary care clinic (PCC) based in Chilliwack, British Columbia.

Methods:

This prospective cross-sectional study included all patients referred to the PCC pharmacist over 12 months (May 2015 to April 2016). Data regarding the source/reason for referral, patient demographics, medical problems/medications and number/category of identified drug therapy concerns (DTCs) were collected.

Results:

A total of 137 referrals were received. Mean age was 60 years and 59% were female. Twenty patients (15%) did not attend their appointment. Fifty-eight percent were new clinic patients identified using a Medication Risk Assessment Questionnaire (MRAQ), 30% were from PCC clinicians and 12% were from community family physicians. The most common reason for referral was for a medication review (82%). Median number of medical problems and medications per patient were 7 (interquartile range [IQR] 5) and 11 (IQR 7.5), respectively. A total of 460 DTCs were identified (median 4 per patient, IQR 3.5), of which 34% were medication without an indication and 28% an untreated indication.

Discussion and Conclusion:

The most common source of referrals to a PCC pharmacist was for medication reviews of new patients using an MRAQ. Most referred patients had multiple medical problems and polypharmacy, and few were referred for disease-specific management. The number of DTCs per patient was variable and, despite polypharmacy being commonplace, almost one-third of patients had an untreated indication.
Demonstration of therapeutic window of Cerebrolysin in embolic stroke: A prospective, randomized, blinded, and placebo-controlled study
Authors: Zhang Li , Chopp Michael , Lu Mei , Zhang Talan , Li Chao , Winter Stefan , Brandstaetter Hemma , Doppler Edith , Meier Dieter , Pabla Pardeep , Zhang Zheng G
Published: April 2017

Background and aims

In an effort to characterize the effects of Cerebrolysin for treatment of stroke that are essential for successful clinical translation, we have demonstrated that Cerebrolysin dose dependently enhanced neurological functional recovery in experimental stroke. Here, we conduct a prospective, randomized, placebo-controlled, blinded study to examine the therapeutic window of Cerebrolysin treatment of rats subjected to embolic stroke.

Methods

Male Wistar rats age 3–4 months (n = 100) were subjected to embolic middle cerebral artery occlusion. Animals were randomized to receive saline or Cerebrolysin daily for 10 consecutive days starting 4, 24, 48, and 72 h after middle cerebral artery occlusion. Neurological outcome was measured weekly with a battery of behavioral tests (adhesive removal test, modified neurological severity score (mNSS), and foot-fault test). Global test was employed to assess Cerebrolysin effect on neurological recovery with estimation of mean difference between Cerebrolysin and control-treated groups and its 95% confidence interval in the intent-to-treat population, where a negative value of the mean difference and 95% confidence interval < 0 indicated a significant treatment effect. All rats were sacrificed 28 days after middle cerebral artery occlusion and infarct volume was measured.

Results

Cerebrolysin treatment initiated within 48 h after middle cerebral artery occlusion onset significantly improved functional outcome; mean differences and 95% confidence interval were −11.6 (−17.7, −5.4) at 4 h, −7.1 (−13.5, −0.8) at 24 h, −8.4 (−14.2, −8.6) at 48 h, and −4.9 (−11.4, 1.5) at 72 h. There were no differences on infarct volume and mortality rate among groups.

Conclusions

With a clinically relevant rigorous experimental design, our data demonstrate that Cerebrolysin treatment effectively improves stroke recovery when administered up to 48 h after middle cerebral artery occlusion.
Segmenting subregions of the human hippocampus on structural magnetic resonance image scans: An illustrated tutorial
Authors: Dalton Marshall A. , Zeidman Peter , Barry Daniel N. , Williams Elaine , Maguire Eleanor A.
Published: April 2017

Background:

The hippocampus plays a central role in cognition, and understanding the specific contributions of its subregions will likely be key to explaining its wide-ranging functions. However, delineating substructures within the human hippocampus in vivo from magnetic resonance image scans is fraught with difficulties. To our knowledge, the extant literature contains only brief descriptions of segmentation procedures used to delineate hippocampal subregions in magnetic resonance imaging/functional magnetic resonance imaging studies.

Methods:

Consequently, here we provide a clear, step-by-step and fully illustrated guide to segmenting hippocampal subregions along the entire length of the human hippocampus on 3T magnetic resonance images.

Results:

We give a detailed description of how to segment the hippocampus into the following six subregions: dentate gyrus/Cornu Ammonis 4, CA3/2, CA1, subiculum, pre/parasubiculum and the uncus. Importantly, this in-depth protocol incorporates the most recent cyto- and chemo-architectural evidence and includes a series of comprehensive figures which compare slices of histologically stained tissue with equivalent 3T images.

Conclusion:

As hippocampal subregion segmentation is an evolving field of research, we do not suggest this protocol is definitive or final. Rather, we present a fully explained and expedient method of manual segmentation which remains faithful to our current understanding of human hippocampal neuroanatomy. We hope that this ‘tutorial’-style guide, which can be followed by experts and non-experts alike, will be a practical resource for clinical and research scientists with an interest in the human hippocampus.
Adjunctive ketamine in electroconvulsive therapy: Updated systematic review and meta-analysis
Authors: McGirr Alexander , Berlim Marcelo T. , Bond David J. , Chan Peter Y. , Yatham Lakshmi N. , Lam Raymond W.
Published: April 2017

Background

Ketamine has emerged as a novel therapeutic agent for major depressive episodes, spurring interest in its potential to augment electroconvulsive therapy (ECT).

Aims

We sought to update our preliminary systematic review and meta-analysis, focusing on randomised controlled trials (RCTs) involving an index course of ECT, and testing the hypothesis that lack of efficacy is due to barbiturate anaesthetic co-administration.

Method

We searched EMBASE, CENTRAL and Medline to identify RCTs examining the efficacy of ketamine during a course of ECT. Data were synthesised from ten trials (ketamine group n = 333, comparator group n = 269) using pooled random effects models.

Results

Electroconvulsive therapy with ketamine was not associated with greater improvements in depressive symptoms or higher rates of clinical response or remission, nor did it result in pro-cognitive effects. This held true when limiting analysis to trials without barbiturate anaesthetic co-administration. Increased rates of confusion were reported.

Conclusions

Overall, our analyses do not support using ketamine over other induction agents in ECT.
Comparison of Metabolic Risk Factors for Liver Cancer Among Men and Women in Guatemala
Authors: Rivera-Andrade Alvaro , Kroker-Lobos Maria Fernanda , Lazo Mariana , Freedman Neal , Groopman John , Guallar Eliseo , Mendoza-Montano Carlos , McGlynn Katherine , Smith Josh , Ramirez-Zea Manuel
Published: April 2017

Abstract 13

Background:

The proportion of liver cancer (LC) that is linked to metabolic risk factors has been increasing in many countries. Guatemala has the highest reported incidence of LC in the Americas, 1 but the prevalence of metabolic risk factors is not clear. We undertook this work to examine the prevalence of metabolic risk factors for LC in Guatemala by sex and residence.

Methods:

We conducted a cross-sectional study of 461 adults older than 40 years who resided in rural and urban areas. Risk factors were defined by using physical exam and laboratory data, including anthropometry, blood pressure, fasting plasma glucose, serum liver enzymes, and lipids. Fatty liver disease (FLD) was defined as a fatty liver index score of > 60 and liver fibrosis (LF) as defined by a FIB-4 score of > 2.67. 2 , 3

Results:

Among participants, 66% resided in rural areas and 57% were women. Mean ages of men and women were 58.0 ± 11.3 and 53.4 ± 9.8 years, respectively. Compared with men, women had higher prevalence of obesity (15% v 41%; P ≤ .001), metabolic syndrome (46% v 74%; P < .001), and FLD (67% v 52%; P < .001), but not LF (6% v 4%; P = .238). Compared with men and women from rural areas, those from urban areas had higher prevalence of diabetes (10% v 27%; P = .002; and 14% v 32%; P < .001) FLD (42% v 67%; P < .001; and 59% v 79%; P < .001), and metabolic syndrome (37% v 58%; P = .005; and 69% v 81%; P = .032), respectively. There was no difference in prevalence of LF by area among either men (6% v 6%; P = .86) or women (3% v 4%; P = .75).

Conclusion:

This study highlights a high prevalence of metabolic risk factors for LC in Guatemala, especially among women in urban areas.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Alvaro Rivera-Andrade No relationship to disclose Maria Fernanda Kroker-Lobos No relationship to disclose Mariana Lazo No relationship to disclose Neal Freedman No relationship to disclose John Groopman No relationship to disclose Eliseo Guallar No relationship to disclose Carlos Mendoza-Montano No relationship to disclose Katherine McGlynn No relationship to disclose Josh Smith Research Funding: Abbott Nutrition Manuel Ramirez-Zea No relationship to disclose
Incidence, Persistence, and Determinants of Human Papillomavirus: A Prospective Cohort Study of HIV-Negative Nigerian Women
Authors: Adebamowo Sally N. , Odutola Michael , Famooto Ayotunde , Dareng Eileen , Adebayo Amos , Achara Peter , Alabi Bunmi , Obende Kayode , Offiong Richard , Ologun Sanni , Adebamowo Clement A. ,   ACCME Research Group
Published: April 2017

Abstract 63

Background:

Cervical cancer is the second most common cancer in Africa. Persistent high-risk human papillomavirus (HRHPV) infection is a necessary cause but little is known about the persistence and associated risk factors of HRHPV infection in African women. We undertook this work to determine risk factors and the incidence of HPV infection in Nigerian women.

Methods:

ACCME is a multicenter, prospective cohort study of host germline, cervical somatic and HRHPV genomics, epigenomics, and vaginal microenvironment and their association with HPV. From February 2014 to January 2016, 10,000 HIV-negative women were enrolled in the cohort and are being observed every 6 months. We used SPF25/LiPA10 to characterize HPV infection and defined persistent infection as two consecutive positive tests performed at least 12 months apart. Logistic regression models were used to estimate associations between risk factors and persistent HPV.

Results:

The mean (± standard deviation) age of study participants at baseline was 40 (± 10) years, and mean (± standard deviation) vaginal pH was 5.2 (± 0.6). Approximately 42% of participants were positive for any HPV and 21% had persistence of any HPV infection. Some (35%) participants had multiple infections with any HPV. Approximately 54% of those with persistent any HPV infection had HRHPV—HPV type 52 (25%) and type 18 (15%) were the most prevalent and persistent HRHPV types. Incidence of any HPV infection was 6.6 per 1,000 person-months, whereas that of HRHPV was 2.6 per 1,000 person-months. Age, body mass index, education level, marital and socioeconomic status, and total number of lifetime sexual partners were associated with HPV infection in these women.

Conclusion:

We defined the incidence, risk factors, and most common types of HRHPV in a large cohort of women in West Africa.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Sally N. Adebamowo No relationship to disclose Michael Odutola No relationship to disclose Ayotunde Famooto No relationship to disclose Eileen Dareng No relationship to disclose Amos Adebayo No relationship to disclose Peter Achara No relationship to disclose Bunmi Alabi No relationship to disclose Kayode Obende No relationship to disclose Richard Offiong No relationship to disclose Sanni Ologun No relationship to disclose Clement A. Adebamowo Speakers' Bureau: Merck