bluuebunny/crossref_metadata_2025 huggingface dataset:
The Canadian Alcohol Policy Evaluation project: Findings from a review of provincial and territorial alcohol policies
Authors: Vallance Kate , Stockwell Tim , Wettlaufer Ashley , Chow Clifton , Giesbrecht Norman , April Nicole , Asbridge Mark , Callaghan Russell , Cukier Samantha , Hynes Geoff , Mann Robert , Solomon Robert , Thomas Gerald , Thompson Kara
Published: February 2021

Introduction

Effective alcohol control measures can prevent and reduce alcohol‐related harms at the population level. This study aims to evaluate implementation of alcohol policies across 11 evidence‐based domains in Canada's 13 jurisdictions.

Methods

The Canadian Alcohol Policy Evaluation project assessed all provinces and territories on 11 evidence‐based domains weighted for scope and effectiveness. A scoring rubric was developed with policy and practice indicators and peer‐reviewed by international experts. The 2017 data were collected from publicly‐available regulatory documents, validated by government officials, and independently scored by team members.

Results

The average score for alcohol policy implementation across Canadian provinces and territories was 43.8%; Ontario had the highest (63.9%) and Northwest Territories the lowest (38.4%) jurisdictional scores. Only six of 11 policy domains had average scores above 50% with Monitoring and Reporting scoring the highest (62.8%) and Health and Safety Messaging the lowest (25.7%). A 2017 provincial/territorial current best practice score of 86.6% was calculated taking account of the highest scores for any individual policy indicators implemented in at least one jurisdiction across the country.

Discussion and Conclusions

Most of the evidence‐based alcohol policies assessed by the Canadian Alcohol Policy Evaluation project were not implemented across Canadian provinces and territories as of 2017, and many provinces showed declining scores since 2012. However, the majority of policies assessed have been implemented in at least one jurisdiction. Improved alcohol policies to reduce related harm are therefore achievable and could be implemented consistently across Canada.
Tissue harmonic versus contrast‐enhanced harmonic endoscopic ultrasonography for the diagnosis of pancreatic tumors: Prospective multicenter study
Authors: Omoto Shunsuke , Kitano Masayuki , Fukasawa Mitsuharu , Ashida Reiko , Kato Hironari , Shiomi Hideyuki , Sugimori Kazuya , Kanno Atsushi , Chiba Yasutaka , Takano Shinichi , Yamamoto Naoki , Ezaki Takeshi , Miwa Haruo , Yokomura Akitaka , Hoshikawa Masato , Tanaka Takamitsu , Kudo Masatoshi
Published: February 2021

Objectives

This prospective multicenter study aimed to assess and compare the accuracy of tissue harmonic endoscopic ultrasonography (TH‐EUS) and contrast‐enhanced harmonic endoscopic ultrasonography (CH‐EUS) for differentiating pancreatic carcinoma from other pancreatic tumors.

Methods

Consecutive patients with solid pancreatic tumors were prospectively enrolled between August 2013 and December 2014. To assess the accuracy of TH‐EUS and CH‐EUS, we compared four parameters of TH‐EUS (fuzzy edge, irregular periphery, hypoechogenicity, and heterogeneous internal echogenicity) and four parameters of CH‐EUS (hypoenhancement and heterogeneous enhancement in the early and late phases, respectively) to investigate which parameter of each method was most suitable to diagnose pancreatic carcinomas. Interobserver agreement and the diagnostic ability of pancreatic carcinoma using TH‐EUS and CH‐EUS were assessed and compared.

Results

A total of 204 patients were enrolled. For the diagnosis of pancreatic carcinoma, interobserver agreement by experts and nonexperts was 0.33–0.50 and 0.35–0.50 for TH‐EUS, respectively, and 0.72–0.74 and 0.20–0.54 for CH‐EUS, respectively. Irregular periphery was the most accurate diagnostic parameter among TH‐EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 95.0%, 42.9%, and 78.9%, respectively. Late phase hypoenhancement was the most accurate diagnostic parameter among CH‐EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 90.8%, 74.6%, and 85.8%, respectively. The accuracy of CH‐EUS (late phase hypoenhancement) for diagnosis of pancreatic carcinoma was significantly higher than that of TH‐EUS (irregular periphery) (p < 0.001).

Conclusion

In comparison with TH‐EUS, CH‐EUS increased the diagnostic ability and reproducibility for the diagnosis of pancreatic carcinoma. UMIN (000011124).
Communication changes when infants begin to walk
Authors: West Kelsey L. , Iverson Jana M.
Published: February 2021

Learning to walk allows infants to travel faster and farther and explore more of their environments. In turn, walking may have a cascading effect on infants’ communication and subsequent responses from caregivers. We tested for an inflection point—a dramatic shift in the developmental progression—in infant communication and caregiver responses when infants started walking. We followed 25 infants longitudinally over 7 months surrounding the onset of walking (mean walk onset age = 11.76 months, SD = 1.56). After learning to walk, the pace of gesture growth (but not vocalization growth) increased substantially, and infants increasingly coordinated gestures and vocalizations with locomotion (e.g., by walking to a caregiver and showing off a toy bear). Consequently, caregivers had more opportunities to respond contingently to their infants during walking months compared to crawling months (e.g., “What did you find? Is that your bear?”). Changes in communication were amplified for infants who began walking at older ages, compared to younger walkers. Findings suggest that learning to walk marks a point in development when infants actively communicate in new ways, and consequently elicit rich verbal input from caregivers.
UBE3A reinstatement as a disease‐modifying therapy for Angelman syndrome
Authors: Elgersma Ype , Sonzogni Monica
Published: February 2021

Half a century ago, Harry Angelman reported three patients with overlapping clinical features, now well known as Angelman syndrome. Angelman syndrome is caused by mutations affecting the maternally inherited UBE3A gene, which encodes an E3‐ubiquitin ligase that is critical for typical postnatal brain development. Emerging evidence indicates that UBE3A plays a particularly important role in the nucleus. However, the critical substrates that are controlled by UBE3A remain elusive, which hinders the search for effective treatments. Moreover, given the multitude of signalling mechanisms that are derailed, it is unlikely that targeting a single pathway is going to be very effective. Therefore, expectations are very high for approaches that aim to restore UBE3A protein levels. A particular promising strategy is an antisense oligonucleotide approach, which activates the silenced paternal UBE3A gene. When successful, such treatments potentially offer a disease‐modifying therapy for Angelman syndrome and several other neurodevelopmental disorders.

What this paper adds

Loss of UBE3A affects multiple signalling pathways in the brain.

Emerging evidence suggests that UBE3A plays a critical role in the cell nucleus.

Trials using antisense oligonucleotides to restore UBE3A levels are continuing.
On the ability of experimental impact measures to predict tooth injuries in an ex vivo swine model
Authors: Houg Kathryn P. , Adanty Kevin , MacGillivray Samantha R. , McAllister Lowell , Levin Liran , Alexiou Maria , Graf Daniel , Romanyk Dan L. , Dennison Christopher R.
Published: February 2021

Background/Aim

Impact to the orofacial region, in particular teeth, is a frequent incident leading to injury in many sports and can result in health and economic costs for the injured individual. The majority of previous work has applied synthetic models such as plaster or stone, to form analogs of relevant structures to study the potential for impact‐induced injury. Biomechanical studies that have applied tissue models (animal or human) for the purpose of determining the biomechanical measures associated with dental injury are rare. The aim of this study was to apply a simple ex vivo model based on swine dentition to ascertain which of a select list of measurable quantities associated with impact mechanics could predict luxation and fracture of teeth due to impact.

Methods

Mandibular central incisors of ex vivo swine dentitions were impacted using a linear drop tower with heights ranging from 1.20 m to 2.42 m. Seven mechanical predictors were assessed at impact and were then subjected to binary logistic regression techniques to determine which was the best predictor of luxations or fractures of the teeth.

Results

Of the seven mechanical predictors, (1) the velocity of the impacting body (R2 = 0.477), (2) a proxy measure for the change in kinetic energy of the impacting body (R2 = 0.586), and (3) the approximate energy absorbed by the tissue (R2 = 0.722) were found to be statistically significantly different (p < .05), offering the greatest specificity as indicated by receiver operator characteristics. Other measures that are frequently used in impact mechanics, including peak linear acceleration and velocity change, were not statistically significant predictors of tooth injury.

Conclusion

Identifying mechanical predictors for dental injury of unprotected teeth provides a first step in understanding which aspects of an impact event attribute to dental injury and can lay the foundation for future studies that examine alteration in injury mechanics associated with protection devices.
The impact of lenalidomide maintenance on second‐line chemotherapy in transplant eligible patients with multiple myeloma
Authors: Cherniawsky Hannah M. , Kukreti Vishal , Reece Donna , Masih‐Khan Esther , McCurdy Arleigh , Jimenez‐Zepeda Victor H. , Sebag Michael , Song Kevin , White Darrell , Stakiw Julie , LeBlanc Richard , Reiman Anthony , Louzada Martha , Aslam Muhammad , Kotb Rami , Gul Engin , Atenafu Eshetu , Venner Christopher P.
Published: February 2021

Objectives

To understand the impact of therapy sequencing on progression‐free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low‐dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting.

Methods

We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second‐line therapy, 575 patients were included.

Results

Patients treated with LM had statistically similar 2nd PFS when re‐exposed to lenalidomide in second‐line therapy compared to those receiving non‐lenalidomide‐containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second‐line therapy than their non‐LM counterparts.

Conclusion

Our data suggest that patients progressing on LM who receive lenalidomide‐containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non‐lenalidomide‐containing second‐line regimens. Identification of patients mostly likely to benefit from further lenalidomide‐containing therapy is paramount.
A change of mind: Globus pallidus activity and effective connectivity during changes in choice selections
Authors: Fiore Vincenzo G. , Guertler Ann‐Cathrin V. , Yu Ju‐Chi , Tatineni Chandana C. , Gu Xiaosi
Published: February 2021

The basal ganglia are a group of interconnected subcortical nuclei that plays a key role in multiple motor and cognitive processes, in a close interplay with several cortical regions. Two conflicting theories postulate that the basal ganglia pathways can either foster or suppress the cortico–striatal output or, alternatively, they can stabilize or destabilize the cortico–striatal circuit dynamics. These different approaches significantly impact the understanding of observable behaviours and cognitive processes in healthy, as well as clinical populations. We investigated the predictions of these models in healthy participants (N = 28), using dynamic causal modeling of fMRI BOLD activity to estimate time‐ and context‐dependent changes in the indirect pathway effective connectivity, in association with repetitions or changes of choice selections. We used two multi‐option tasks that required the participants to adapt to uncontrollable environmental changes, by performing sequential choice selections, with and without value‐based feedbacks. We found that, irrespective of the task, the trials that were characterized by changes in choice selections (switch trials) were associated with a neural response that mostly overlapped with a network commonly described for the encoding of uncertainty. More interestingly, dynamic causal modeling and family‐wise model comparison identified with high likelihood a directed causal relation from the external to the internal part of the globus pallidus (i.e., the short indirect pathway in the basal ganglia), in association with the switch trials. This finding supports the hypothesis that the short indirect pathway in the basal ganglia drives instability in the network dynamics, resulting in changes in choice selection.
Ecological mechanism of climate‐mediated selection in a rapidly evolving invasive species
Authors: Mushegian Alexandra A. , Neupane Naresh , Batz Zachary , Mogi Motoyoshi , Tuno Nobuko , Toma Takako , Miyagi Ichiro , Ries Leslie , Armbruster Peter A.
Published: February 2021

Recurring seasonal changes can lead to the evolution of phenological cues. For example, many arthropods undergo photoperiodic diapause, a programmed developmental arrest induced by short autumnal day length. The selective mechanisms that determine the timing of autumnal diapause initiation have not been empirically identified. We quantified latitudinal clines in genetically determined diapause timing of an invasive mosquito, Aedes albopictus, on two continents. We show that variation in diapause timing within and between continents is explained by a novel application of a growing degree day (GDD) model that delineates a location‐specific deadline after which it is not possible to complete an additional full life cycle. GDD models are widely used to predict spring phenology by modelling growth and development as physiological responses to ambient temperatures. Our results show that the energy accumulation dynamics represented by GDD models have also led to the evolution of an anticipatory life‐history cue in autumn.
Letter: Trophic interactions regulate peatland carbon cycling
Authors: Wyatt Kevin H. , McCann Kevin S. , Rober Allison R. , Turetsky Merritt R.
Published: February 2021

Peatlands are the most efficient natural ecosystems for long‐term storage of atmospheric carbon. Our understanding of peatland carbon cycling is based entirely on bottom‐up controls regulated by low nutrient availability. Recent studies have shown that top‐down controls through predator‐prey dynamics can influence ecosystem function, yet this has not been evaluated in peatlands to date. Here, we used a combination of nutrient enrichment and trophic‐level manipulation to test the hypothesis that interactions between nutrient availability (bottom‐up) and predation (top‐down) influence peatland carbon fluxes. Elevated nutrients stimulated bacterial biomass and organic matter decomposition. In the absence of top‐down regulation, carbon dioxide (CO2) respiration driven by greater decomposition was offset by elevated algal productivity. Herbivores accelerated CO2 emissions by removing algal biomass, while predators indirectly reduced CO2 emissions by muting herbivory in a trophic cascade. This study demonstrates that trophic interactions can mitigate CO2 emissions associated with elevated nutrient levels in northern peatlands.
Status of clinical research in neurology in Germany—A national survey
Authors: Lohmann Lisa , Lammerskitten Anna , Korsen Melanie , Dodel Richard , Gaul Charly , Hamer Hajo M. , Kleineberg Nina N. , Ludolph Albert C. , Mayer Geert , Poli Sven , Saur Dorothee , Steinhoff Bernhard J. , Timmermann Lars , Klotz Luisa , Meuth Sven G.
Published: February 2021

Background and purpose

To provide an overview on the status of clinical research in neurology in Germany.

Methods

German university hospitals, nonuniversity hospitals, and neurological medical practices were surveyed regarding their clinical research activities during the period 2013 to 2017.

Results

Fifty percent of university hospitals, 10.6% of nonuniversity hospitals, and 5.2% of medical practices in Germany responded to our questionnaire. More than 80% of the clinical studies conducted have been phase III/IV and noninterventional trials (NISs), whereas <1% have been phase I and 3.5% investigator‐initiated trials (IITs). University hospitals have conducted most of the phase II–IV trials. NISs have been predominantly performed by medical practices. Fifty‐six percent of the university hospitals and less of the nonuniversity institutions confirmed the implementation of standard operating procedures (SOPs). In university hospitals, on average, 11 physicians had acquired a good clinical practice certificate. Overall, 43% of all trials have been performed in neuroimmunology.

Conclusions

The status of clinical research in neurology in Germany is predominated by NISs and late‐phase trials, potentially due to a general lack of easily accessible funding, which leads to a highly competitive environment and fewer opportunities to perform early‐phase clinical trials as well as IITs. Our results indicate that there is substantial need for structured support for creating and implementing SOPs to maintain quality standards and guarantee uniformity of performance. This survey assessed many aspects of clinical research and serves as guidance for providing ideas for structured improvement of clinical research in neurology in Germany.
Morphological variability of the atrioventricular valve cusps in the equine heart
Authors: De Silva Margherita , Tagliavia Claudio , Galiazzo Giorgia , Gifuni Giovanni , Caiazza Michele , Chiocchetti Roberto , Grandis Annamaria
Published: February 2021

Background

The morphometric studies of the atrioventricular valves are still limited in the horse.

Objectives

To investigate the anatomy of the atrioventricular valves in the horse, focusing on the morphometric features of the valvular leaflets and the tendinous cords. We hypothesised that accessory leaflets occur commonly and exist as independent structures in the atrioventricular valves of the horse.

Study design

Descriptive anatomical study.

Methods

Twenty normal hearts from slaughtered half‐bred horses were used. The cardiac weight and circumference were recorded. The atrioventricular valves were exposed by excision of the atria, and the tricuspid and mitral annular diameters and circumferences were measured; the number of leaflets and tendinous cords for each atrioventricular ostium were then counted. The atrioventricular valves were isolated and the width, height and thickness of each leaflet were measured.

Results

In addition to the principal leaflets, accessory leaflets were identified in 39 of 40 cardiac valves, 2 to 6 accessory leaflets for the mitral valve and 1 to 4 for the tricuspid valve. All the accessory leaflets were separated from the adjacent leaflets at their insertion. They were narrower and thinner than the principal leaflets, and were attached to a single papillary muscle; 95% of the accessory leaflets had two tendinous cords shared with the adjacent leaflets while a minority (34%) had their own specific tendinous cord.

Main limitations

Lack of signalment data from the study population.

Conclusions

Supernumerary leaflets occurred commonly in the atrioventricular valves of the horse and appeared as independent structures. The clinical relevance of increased numbers of commissures that result from accessory leaflets and their relationship with valvular regurgitation are currently unknown.
Knowledge representation and acquisition using R‐numbers Petri nets considering conflict opinions
Authors: Mou Xun , Zhang Qi‐Zhen , Liu Hu‐Chen , Zhao Jianshen
Published: February 2021

As a vital modelling technique, fuzzy Petri nets (FPNs) have been widely used in various areas for knowledge representation and reasoning. However, the conventional FPNs have many deficiencies in representing inaccurate knowledge, acquiring knowledge parameters and conducting approximate reasoning when used in the real world. In this article, a new version of FPNs, called R‐numbers Petri nets (RPNs), is proposed to overcome the shortcomings and enhance the effectiveness of FPNs. Based on R‐numbers, expert knowledge is depicted in the form of weighted R‐numbers production rules. The interrelationships among input places (or transitions) are modelled by the R‐numbers Maclaurin symmetric mean operator in the knowledge reasoning process. In addition, the conflict opinions of experts are handled with the proposed RPN model in order to obtain more precise knowledge parameters. Finally, the effectiveness and practicality of the proposed RPNs are illustrated by a realistic example concerning reliability analysis of an electric vehicle motor.
Development of some techniques for solving system of linear and nonlinear equations via hybrid algorithm
Authors: Kumar Nirmal , Shaikh Ali Akbar , Mahato Sanat Kumar , Bhunia Asoke Kumar
Published: February 2021

The objective of this article is to introduce several new methods or techniques for solving simultaneous linear and nonlinear system of equations with the help of a new hybrid algorithm based on advanced quantum behaved particle swarm optimization and the concept of binary tournamenting process. Depending on different options of binary tournamenting, six different variants of hybrid algorithms are proposed. To examine the effectiveness of the proposed hybrid algorithms five well known benchmark bound‐constrained optimization problems are solved. Among the six different variants of hybrid algorithms, the best algorithm is selected on the basis of their performances in these problems. This best algorithm is then applied in solving simultaneous linear and nonlinear system of equations transforming these equations into optimization problems. In case of linear system, just two systems are solved while in case of nonlinear system seven complicated problems are solved and finally a comparison of best found solutions are estimated with the same of existing algorithms provided in the literature.
Classification of Parkinson disease using binary Rao optimization algorithms
Authors: Sharma Suvita Rani , Singh Birmohan , Kaur Manpreet
Published: February 2021

Rao algorithms are recently proposed optimization algorithms used to solve optimization problems. These algorithms are based on the best and the worst solutions, which are computed during the optimization process. However, these algorithms apply to continuous problems only. In this article, the binary versions of Rao algorithms are proposed, which can be used for solving feature selection problems. These are applied to four publicly available Parkinson's disease datasets. Besides providing an optimal set of features, the k parameter of the k‐nearest neighbour classifier is also optimized by the proposed approach. The performance of these algorithms has been measured taking an average of 30 independent runs using a 10‐fold cross‐validation procedure. Also, a comparison of the performance has been made with the other state of the art methods. Significance analysis of these algorithms has been made with the Friedman rank test.
Project performance prediction model linking agility and flexibility demands to project type
Authors: de Oliveira Marco Aurélio , Dalla Valentina Luiz V. O. , Futami André Hideto , Possamai Osmar , Flesch Carlos Alberto
Published: February 2021

The main purpose of this work is the development of a performance prediction model of projects, considering the influence of the leadership style and organizational factors on the agility and flexibility of the organization. The motivation of this work is the absence in the literature of a model to establish the relationship among leadership and agility factors, by means of the integration of prediction and sensitivity analysis capacities. The originality of this work lies on the presentation of a general model integrating both capacities, dedicated to the analysis of different kind of projects. The first part of the study deals with a literature review regarding the components of leadership, organizational structure, agility, flexibility and organizational factors and the intrinsic relationship among them. This information is the basis of the framework of this study that serves for the construction of the model. Artificial intelligence (AI) techniques and statistical tools are used for modeling purposes. From the model application, it is possible to identify under which conditions of leadership style and organizational factors there are the highest chances of high project performances. The main results are the characterization of agility and flexibility demands for each type of project, the understanding of how leadership affects agility and flexibility, and the impacts on the project performance.
Cormorant predation effects on fish populations: A global meta‐analysis
Authors: Ovegård Maria K. , Jepsen Niels , Bergenius Nord Mikaela , Petersson Erik
Published: February 2021

This paper provides the results from the first meta‐analysis to examine the impact of cormorant (Phalacrocoracidae) predation on fish. It is based on a systematic search of literature, covering studies using significance‐based hypotheses tests on the relation between fish parameters and cormorant abundance. The results show that extensive research on cormorant diet exists, but few studies use statistical hypotheses testing to examine the effect on fish populations. In total, 603 publications were identified from titles and abstracts, to include the interaction between cormorants and fish. From these, 27 articles tested fish population parameters against cormorant predation, whereof 22 could be included in analyses. The effect size was defined negative in cases when cormorant numbers or presence reduced fish numbers or biomasses, or when individual fish sizes decreased, and vice versa for a positive effect. In a hierarchical dependence model, the combined effect of cormorant predation on fish was negative, but the overall effect was not significant at the 95% confidence level (−0.169, 95% C.L. −0.505 to 0.167, p = .256, df = 5.26). A covariate analysis revealed a difference in predatory effects between fish prey taxa (p =  .006,   df = 5.73), but no difference in effect sizes between study type, foraging habitat, or response variable measured. The meta‐analysis reveals a complex interaction between cormorants and fish, but adds to the consensus on the importance of considering cormorant predatory effects in research, conservation actions, ecosystem‐based management, and environmental monitoring.
Cold offshore area provides a favorable feeding ground with lipid‐rich foods for juvenile Japanese sardine
Authors: Yasuda Tohya , Kitajima Satoshi , Hayashi Akira , Takahashi Motomitsu , Fukuwaka Masa‐aki
Published: February 2021

Japanese sardine (Sardinops melanostictus) in the Sea of Japan expanded their distribution from the coast to offshore with an increase in population biomass; however, little is known about the suitability of the offshore habitat for this species. Using lipid analysis, this study compared the body condition of juvenile sardine between an area off the Noto Peninsula (offshore) and the Tsushima Strait (coast), with respect to habitat conditions during the summer, from 2015 to 2017. Sardine in the offshore area had larger bodies and higher lipid contents than those in the coastal area. Regarding the sardine diet, lipid content of the offshore zooplankton was clearly higher than that of the coastal zooplankton. Hence, we found a positive effect of this dietary lipid content on sardine lipid content, suggesting that these lipid measurements could explain the trophic relationship between sardine and zooplankton. The higher lipid content in offshore zooplankton was mainly attributed to the abundance of large‐sized copepods and lower water temperatures. Such lipid measurements might involve habitat‐specific characteristics of zooplankton assemblage. In conclusion, compared to the coastal area, the offshore area is considered a more favorable habitat for the sardine in terms of lipid availability.
A POI‐Constrained Space‐Time Accessibility Model
Authors: Wu Jing , Zou Qiang , Claramunt Christophe , Cheng Penggen , Gu Huaqi
Published: February 2021

Space‐time accessibility usually denotes the ability or potential to reach some destinations of value according to some given spatial and temporal constraints. While most of space‐time accessibility models so far recognize that space and time dimensions constrain the way humans might perform some activities at some given locations, additional semantics such as the ones exhibited by points of interest (POI) are most often not taken into account within the search space. Relying on concepts behind Time Geography, this article introduces a high‐dimensional space‐time network modelling approach that takes into account a series of POI constraints. We developed an Alternating Direction Method of Multipliers (ADMM) solution search process, and implemented a POI‐constrained accessibility model. The whole framework is practically implemented by an algorithmic approach. The potential of our work is finally illustrated by a practical example applied to the Beijing Happy Valley.
Acquired haemophilia A in the postpartum and risk of relapse in subsequent pregnancies: A systematic literature review
Authors: Dewarrat Natacha , Gavillet Mathilde , Angelillo‐Scherrer Anne , Naveiras Olaia , Grandoni Francesco , Tsakiris Dimitrios A. , Alberio Lorenzo , Blum Sabine
Published: February 2021

Background

About 1%–5% of acquired haemophilia A cases affect mothers in the postpartum setting.

Aims

This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies.

Methods

Report of two cases and literature study (1946–2019), yielding 73 articles describing 174 cases (total 176 cases).

Results

Patients were aged 29.9 years (17–41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0–308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was <1% (range 0%–8%). FVIII inhibitor was documented in 75.4% cases (median titre of 20 BU/ml, range 1–621). Haemostatic treatment was necessary in 57.1% using fresh frozen plasma (16%), factor concentrate (27.6%) and/or bypassing agents (37.4%). Immunosuppressive treatment was administered in 90.8%, mostly steroids (85.3%), alone or combined with immunosuppressants (27%). Rituximab was used mostly as a second line treatment. Only 24 patients (13.6%) had documented subsequent pregnancies and 6 (22.2%) suffered haemophilia recurrence during pregnancy.

Conclusion

This study allows better definition of: (1) clinical and laboratory characteristics of postpartum acquired haemophilia, (2) response to therapy, and (3) the risk of relapse for subsequent pregnancies.
Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures
Authors: Desprez Dominique , Drillaud Nicolas , Flaujac Claire , Volot Fabienne , Pan‐Petesch Brigitte , Beurrier Philippe , Cussac Vincent , Feugeas Olivier , Pailler Yoann , Callegarin Anamaria , Trossaërt Marc , de Raucourt Emmanuelle
Published: February 2021

Introduction

Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma‐derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018.

Aim

Describe real‐world experience of using rVWF in surgical procedures.

Methods

Sixty‐three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres.

Results

During minor surgeries, the median (range) number of infusions was 1 (1–8) with a preoperative loading dose of 35 (19–56) rVWF IU/kg and a total median dose of 37.5 IU (12–288). During major surgeries, the median (range) number of infusions was only 3 (1–14) with a median preoperative loading dose of 36 IU (12–51) rVWF IU/kg, and a total median dose of 108 IU (22–340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti‐VWF antibodies or adverse events were reported.

Conclusion

This French ‘real‐world’ experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns.
Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study
Authors: Måseide Ragnhild J. , Berntorp Erik , Astermark Jan , Hansen Jessica , Olsson Anna , Bruzelius Maria , Frisk Tony , Aspdahl Magnus , Nummi Vuokko , Tjønnfjord Geir E. , Holme Pål A.
Published: February 2021

Introduction

Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB).

Aim

To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD‐US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia.

Methods

A cross‐sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD‐US and HJHS 2.1.

Results

We assessed 693 joints in 118 patients. HEAD‐US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0–0), knees 0 (0–0) and ankles 0 (0–1). Respectively, by HJHS: elbows 0 (0–1), knees 0 (0–1) and ankles 0 (0–1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD‐US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD‐US correlated strongly with HJHS (elbows r = .70, knees r = .60 and ankles r = .65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD‐US ≥1 point. Moreover, 26% had HJHS findings without HEAD‐US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD‐US.

Conclusion

Overall, the joints attained low scores implying good joint health. HEAD‐US correlated strongly with HJHS. In 5%, HEAD‐US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD‐US, thus not necessarily reflecting arthropathy. HEAD‐US therefore improves the joint assessment in moderate haemophilia.
Exploratory in vitro evaluation of thrombin generation of eptacog beta (recombinant human fviia) and emicizumab in congenital haemophilia A plasma
Authors: Grandoni Jerry , Duretz Véronique , Bonzo Daniel , Evans Sean , Plantier Jean‐Luc
Published: February 2021

Introduction/Aim

Eptacog beta is a recombinant activated human factor VII approved to treat and control bleeding in haemophilia A and B patients with inhibitors. Emicizumab is a factor VIIIa mimetic antibody approved for prophylactic treatment of haemophilia A with and without inhibitors (HAI and HA, respectively). Inhibitor patients treated with emicizumab should expect breakthrough bleeding that requires bypassing agent treatment to restore haemostasis. The aim of this study is to quantify the in vitro thrombin generation induced by the addition of eptacog beta to HAI and HA plasma containing emicizumab.

Methods

Thrombin generation assays were performed using HAI and HA plasma. Thrombin generation parameters were examined using a fixed effects model with inhibitor titre, eptacog beta concentration and emicizumab concentration as main effects, and eptacog beta concentration with inhibitor and emicizumab concentration with inhibitor as interaction effects.

Results

A significant increase in peak thrombin, ETP and velocity was observed when combinations of eptacog beta (0, 1, 2 or 5 µg/ml) and emicizumab (0, 50 or 100 µg/ml) were evaluated in HA and HAI plasma; the effect remained below that observed in Normal Plasma (NP). A small shortening of lag time below that of NP was observed.

Conclusions

Eptacog beta and emicizumab induced thrombin generation in haemophilia A plasma (with and without inhibitors) with the thrombin generation parameters remaining below those of normal plasma. These data provide in vitro proof of concept supporting the concept of use of eptacog beta for the treatment and control of breakthrough bleeding in patients on emicizumab prophylaxis.
Knowledge sharing to support long‐term condition self‐management—Patient and health‐care professional perspectives
Authors: Brand Sarah , Timmons Stephen
Published: February 2021

Background

Increased self‐management is a suggested solution to the burden on health‐care services of long‐term conditions (LTCs). This requires effective sharing of knowledge between health‐care professionals and patients, and is an underexplored area.

Objective

To understand how patients and health‐care professionals (HCPs) share and utilize knowledge in the social context of health‐care interactions within long‐term condition management.

Methods

Thematic analysis of 93 hours of observations of health‐care interactions and 33 semi‐structured interviews involving patients, carers and HCPs.

Results

3 themes were identified: normative social roles, differing professional roles and the value of knowledge. Knowledge sharing was a complex process heavily influenced by social and cultural norms within the health‐care context. Not all knowledge was easily shared within routine health‐care interactions.

Discussion

The social context in which health‐care is practised influences what knowledge is shared and how this is achieved. It favours sharing of clinical knowledge from HCPs to patients and disadvantages patients in their ability to share their unique knowledge based on lived experience of illness. The opportunities for patients to be supported in their knowledge, skills and confidence within routine health‐care interactions are limited.

Conclusion

Both patients and HCPs need support to recognize the characteristics of the social context of health care and their understandings of their roles within this in order for them to move beyond accepted behaviours to develop more effective partnership working.

Patient or Public Contribution

Patients were involved in initial design of the study, particularly ethics of ethnographic observation.
Null effects of the Garcelon harnessing method and transmitter type on soaring raptors
Authors: García Víctor , Iglesias‐Lebrija Juan José , Moreno‐Opo Rubén
Published: February 2021

Tagging wildlife with transmitters is one of the most widely used techniques for research and monitoring. Knowing the possible impact of attaching transmitters to an animal has always concerned researchers; however, most assessments have been directed at the effects of transmitters on behaviour and fitness, and fewer have addressed possible injuries to the individuals. The present study evaluated the physical status of birds tagged with transmitters mounted with a Garcelon‐type backpack harness, from five species of large and medium‐sized soaring raptors in western Europe. The study also assessed the factors determining their duration and outcomes. We sent a survey to the managers of projects involving tagged raptors over a 24‐year period, concerning tracking results and veterinary analyses. We obtained information on 659 birds, of which 196 included clinical evaluation from birds in hand. None of the birds showed marks, injuries or abrasions on their feathers or skin caused by the harness or the transmitter. Therefore, this deployment technique is recommended for soaring birds in general and for others in which the use of a backpack harness is chosen. The duration of the system on the bird depended on the traits of the transmitter, being greater in platform transmitter terminal (PTT) satellites. The device lasted longer in larger species and for a shorter time when tagging nestlings. We propose the need for nestlings to be fitted with harnesses corresponding to the size of their adult conspecifics, distinguishing between males and females. Otherwise, the differential growth between sexes could cause discomfort and more frequent removal attempts of the harness. Our results are especially useful for managers and ethics committees to assess bird welfare risks before issuing official permits.
A laboratory study of the scouting ability of two reciprocating glide path instruments in mesial root canals of extracted mandibular molars
Authors: Pereira R. P. , Alcalde M. P. , Duarte M. A. H. , Vivan R. R. , Bueno C. E. S. , Duque J. A. , Calefi P. H. S. , Bramante C. M.
Published: February 2021

Aim

To evaluate in a laboratory setting the performance of two reciprocating glide path systems, WaveOne Gold Glider (WO) and R‐Pilot (RP), to create a glide path in mesial root canals of mandibular molars and to assess the torsional resistance of instruments after performing the glide path.

Methodology

A total of 60 mesial root canals of extracted human mandibular molars were divided into two groups (n = 30) according to the glide path system to be used. The data from the volume of each canal, acquired by microcomputed tomography (micro‐CT), were validated statistically for the anatomical pairing of the groups. Preparation time, frequency in gaining apical patency, plastic deformation rate of instruments, and canal transportation and centring ability were recorded and compared statistically. The torsional fatigue of the instruments after use was also evaluated. Data were analysed using Fisher’s exact test and Mann–Whitney U‐test with a 5% significance level.

Results

No significant differences were found between groups regarding the time required to perform the glide path, the frequency distributions of the canals classified as patent and the instruments with plastic deformation after use (P > 0.05). No significant differences were found between groups regarding the degree of canal transportation and centring ability at the cervical, middle and apical thirds (P > 0.05). The RP groups had significantly greater maximum torsional strength values compared with the WO groups (P < 0.05). The used WO group had greater angular deflection to fracture when compared to the new WO group (P < 0.05). A significant difference was also found in the percentage of loss of angular deflection in a comparison of the WO group with the RP group (P < 0.05).

Conclusions

The WO and RP instruments performed the same in terms of preparation time, plastic deformation, gaining apical patency, degree of canal transportation and centring ability. The RP instruments had greater torsional strength, less angular deflection and lower percentage of loss in angular deflection than the WO. The used WO group had the greatest angular deflection values.
RETRACTED: Prediction of arrhythmia recurrence after atrial fibrillation ablation in patients with normal anatomy of the left atrium
Authors: Baimbetov Adil K. , Bizhanov Kenzhebek A. , Abzaliyev Kuat B. , Bairamov Binali A. , Yakupova Ilinara A.
Published: February 2021

Background

Enlarged left atrium is an established predictor of atrial fibrillation recurrence after pulmonary vein isolation but arrhythmia recurrence is also observed in patients with normal anatomy of the left atrium. The aim of the study is to evaluate arrhythmia recurrence predictors in patients with normal anatomy of the left atrium.

Methods

The study included 182 patients with normal anatomy of the left atrium who underwent pulmonary vein isolation using catheter ablation. Various parameters were also compared, including age, gender, history of arrhythmia, arterial hypertension, concomitant coronary pathology, echocardiography findings, such as mitral valve and tricuspid valve regurgitation and procedure parameters, between patients with and without relapses. Statistical analysis was performed using the IBM SPSS Statistics‐19 software.

Results

Transthoracic echocardiography was performed by independent specialists with extensive experience. Trans‐esophageal echocardiography was performed before each ablation procedure. Standard trans‐septal puncture was performed under fluoroscopic control. Radiofrequency ablation was performed in the ipsilateral pulmonary vein antrum with a wide capture of nearby lung tissue.

Conclusions

It was concluded that the tricuspid valve regurgitation and arterial hypertension correlate with atrial fibrillation recurrence after pulmonary vein isolation in patients with normal left atrial anatomy.
Non‐pharmacologic treatment of insomnia in primary care settings
Authors: Hrehová Laura , Mezian Kamal
Published: February 2021

Introduction

Prevalence of insomnia is higher in females and increases with higher age. Besides primary insomnia, comorbid sleep disorders are also common, accompanying different conditions. Considering the possible adverse effects of commonly used drugs to promote sleep, a non‐pharmacologic approach should be preferred in most cases. Although generally considered first‐line treatment, the non‐pharmacologic approach is often underestimated by both patients and physicians.

Objective

To provide primary care physicians an up‐to‐date approach to the non‐pharmacologic treatment of insomnia.

Methods

PubMed, Web of Science, and Scopus databases were searched for relevant articles about the non‐pharmacologic treatment of insomnia up to December 2020. We restricted our search only to articles written in English.

Main message

Most patients presenting with sleep disorder symptoms can be effectively managed in the primary care setting. Primary care physicians may use pharmacologic and non‐pharmacologic approaches, while the latter should be generally considered first‐line treatment. A primary care physician may opt to refer the patient to a subspecialist for refractory cases.

Conclusions

This paper provides an overview of current recommendations and up‐to‐date evidence for the non‐pharmacologic treatment of insomnia. This article emphasizes the importance of cognitive‐behavioral therapy for insomnia, likewise, exercise and relaxation techniques. Complementary and alternative approaches are also covered, eg, light therapy, aromatherapy, music therapy, and herbal medicine.