bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecast of Road Traffic Accidents grounded on Rolling optimization Grey Markov Model
Authors: Xu Chengzhen , Zhang Heng , Gong Yanan , Sang Huiyun , Sun Guanglin , Chen Jing
Published: December 2020

This paper recommends the rolling optimization strategy based on the initial data of road traffic accidents, and builds the rolling optimization-grey Markov dynamic prediction model, which can effectively resolve the matter that the precision of accident forecast is influenced by the time benefit of the predicted data. In order to predict the development tendency of road traffic accidents and further improve the prediction precision of random time series, this paper uses Markov chain theory to probe into the transition law between different states. The case study shows that this measure has good forecast precision and practicability in a certain period of time, and can offer Reference for road traffic accident forecast and traffic safety warning.
Natural convection in a Square Enclosure with Partially Active Vertical Wall
Authors: Belazizia Abdennacer , Benissaad Smail , Abboudi Said
Published: December 2020

Steady, laminar, natural convection flow in a square enclosure with partially active vertical wall is considered. The enclosure is filled with air and subjected to horizontal temperature gradient. Finite volume method is used to solve the dimensionless governing equations. The physical problem depends on three parameters: Rayleigh number (Ra =103-106), Prandtl number (Pr=0.71), and the aspect ratio of the enclosure (A=1). The active location takes two positions in the left wall: top (T) and middle (M). The main focus of the study is on examining the effect of Rayleigh number on fluid flow and heat transfer rate. The results including the streamlines, isotherm patterns, flow velocity and the average Nusselt number for different values of Ra. The obtained results show that the increase of Ra leads to enhance heat transfer rate. The fluid particles move with greater velocity for higher thermal Rayleigh number. Also by moving the active location from the top to the middle on the left vertical wall, convection and heat transfer rate are more important in case (M). Furthermore for high Rayleigh number (Ra=106), Convection mechanism in (T) case is principally in the top of the enclosure, whereas in the remaining case it covers the entire enclosure.
A literature survey on humidification dehumidification desalination processes
Authors: Zili-Ghedira Leila , Gouider Hana , Ben Nasrallah Sassi
Published: December 2020

Potable water scarcity can be considered as a challenge nowadays and at least in the nearest future. Many factors contribute to such situation. Common techniques for desalination purpose include multistage flash, multi-effect distillation and reverse osmosis dedicated essentially to large scales. Humidification Dehumidification Desalination systems appear as low scale installations mainly powered by renewable or geothermal energy. This paper focuses on the state of the art of such installations. It discusses their types, their composition and the available models treating them and their outputs, the plants optimization procedures as well as productivity and costs of these systems. The study aims also the futures of such installations.
Flow and heat transfer in anisotropic active foam porous media wall
Authors: Deptulski Rafael , Bennacer Rachid , Vieira Gisele
Published: December 2020

The development of positive-energy buildings is nowadays an important societal challenge and the research objective of many laboratories. Working towards this direction, we describe in the present report the development of active and reactive walls, by employing a multi-fiber, volumetrically structured porous medium. Flow and transfer characterization in such a foam structure is not fully understood due to the strong nonlinearities included. These are amplified by heterogeneities and porosity changes, where the local and global flow affect the thermal field and the resulting heat transfer. Thus, a finite volume method with immersed structure interfaces was implemented to study heat transfer through these media, with the aim of obtaining their ratio equivalent to fluid thermal conductivity (i.e.Nusselt number). Furthermore, our analysis shows that in such active wall constituted by two solid phases, under fixed weight constraints, the optimal value is difficult to predict a priori. Thus, different evolution laws of thermal gradient were studied, resulting in the change of the pore size distribution along some new anisotropic structures, in order to achieve the most one predictive.
Management des pulmonalen Rundherdes
Authors: Schaefer-Prokop Cornelia
Published: December 2020

Pulmonale Rundherde sind fokale rundliche Lungenparenchymverdichtungen, die über 3 mm und unter 3 cm groß sind. Sie haben je nach ihrer Größe, Form, Dichte und Lage, aber auch je nach Komorbidität und Alter des Patienten eine unterschiedliche Bedeutung. Dieser Beitrag beschreibt ihre Diagnostik und die ggf. notwendigen Kontrolluntersuchungen.
The Impact of Narrow-band Imaging on the Pre- and Intra- operative Assessments of Neoplastic and Preneoplastic Laryngeal Lesions. A Systematic Review
Authors: Saraniti Carmelo , Chianetta Enzo , Greco Giuseppe , Mat Lazim Norhafiza , Verro Barbara
Published: December 2020

Introduction Narrow-band imaging is an endoscopic diagnostic tool that, focusing on superficial vascular changes, is useful to detect suspicious laryngeal lesions, enabling their complete excision with safe and tailored resection margins.

Objectives To analyze the applications and benefits of narrow-band imaging in detecting premalignant and malignant laryngeal lesions through a comparison with white-light endoscopy.

Data Synthesis A literature search was performed in the PubMed, Scopus and Web of Science databases using strict keywords. Then, two authors independently analyzed the articles, read the titles and abstracts, and read completely only the relevant studies according to certain eligibility criteria. In total, 14 articles have been included in the present review; the sensitivity, specificity, positive and negative predictive values, and accuracy of pre- and/or intraoperative narrow-band imaging were analyzed. The analysis showed that narrow-band imaging is better than white-light endoscopy in terms of sensitivity, specificity, positive and negative predictive values, and accuracy regarding the ability to identify cancer and/or precancerous laryngeal lesions. Moreover, the intraoperative performance of narrow-band imaging resulted more effective than the in-office performance.

Conclusion Narrow-band imaging is an effective diagnostic tool to detect premalignant and malignant laryngeal lesions and to define proper resection margins. Moreover, narrow-band imaging is useful in cases of leukoplakia that may cover a possible malignant lesion and that cannot be easily assessed with white-light endoscopy. Finally, a shared, simple and practical classification of laryngeal lesions, such as that of the European Laryngological Society, is required to identify a shared lesion management strategy.

Key Points
Recent advances in high-efficiency organic solar cells fabricated by eco-compatible solvents at relatively large-area scale
Authors: Hong Ling , Yao Huifeng , Cui Yong , Ge Ziyi , Hou Jianhui
Published: December 2020

Bulk heterojunction organic solar cells (OSCs) have received considerable attention as a promising clean energy-generating technology because of their low cost and great potential for large-scale commercial manufacturing. With significant advances in new material design, device optimization, and mechanism research, power conversion efficiencies for OSCs continue to increase. However, most top-performing devices are processed by halogenated solvents, which are not suitable for large-area coating technologies. This has become one of the most important barriers to the practical application of OSCs. In this Perspective, we discuss the recent progress in developing highly efficient OSCs via eco-compatible and large-area processing methods, and provide useful guidelines for designing new materials for production applications.
Wettability behavior and anti-icing property of superhydrophobic coating on HTV silicone rubber
Authors: Sun Jiaxiang , He Dongxin , Li Qingquan , Zhang Hongru , Liu Hongshun
Published: December 2020

Composite insulators, which use high temperature vulcanized (HTV) silicone rubber as shed material, are widely applied in transmission lines. Ice accumulation on their surfaces may inflict flashover accident and even massive power outage. In this study, a superhydrophobic (SH) coating on HTV silicone rubber was fabricated by the sol–gel process combined with the plasma jet treatment method. It was found that the as-prepared SH coating exhibited prominent superhydrophobicity and an excellent self-cleaning property with a water contact angle of 160.15°, a contact angle hysteresis of 0.60°, a sliding angle of 1.8°, and a surface free energy of 0.1421 mN/m. The anti-icing behavior of water droplets on the as-prepared SH coating surface was investigated at a low temperature of −30 °C and compared with that of the HTV silicone rubber surface. The results indicated that the freezing time on the SH coating was postponed obviously and was as long as 150 s. The SH coating surface exhibited about 5.6 times delay in freezing at −30 °C compared with the HTV silicone rubber surface. Furthermore, heterogeneous nucleation theory and heat transfer theory were introduced to explain the difference in freezing time between the as-prepared SH coating and HTV silicone rubber. It could be concluded that the SH coating had a large nucleation free energy barrier and a low heat transfer rate between the droplet and the surface and, thus, was able to effectively delay the freezing time.
Magnetization switching depending on magnetic fields applied to ferromagnetic MnAs nanodisks selectively-grown on Si (111) substrates
Authors: Horiguchi Ryoma , Hara Shinjiro , Suzuki Kozaburo , Iida Masaya
Published: December 2020

We report on the applied external magnetic field, B, dependence of a magnetic domain structure and magnetization switching in MnAs nanodisks on AlGaAs nanopillar buffers selectively grown on Si (111) substrates partially covered with dielectric SiO2 thin film mask patterns by selective-area metal–organic vapor phase epitaxy. The results on the B dependence of magnetic domain structures observed by magnetic force microscopy show that the ratio, or percentage, of a single magnetic domain is minimized at B = −1.5 kG in the nanodisks with an area of 4 × 104 nm2 or smaller, although the decrease to the minimum of the ratio is markedly small in the case of the nanodisks with an area of 4 × 104 nm2 or larger at B = −0.5 kG. The angle distribution of magnetization directions shows that the magnetization directions markedly tend to be parallel to the ridge directions of the hexagonal nanodisks, i.e., distribute in steps of ∼60° corresponding to the magnetic easy axes of the hexagonal NiAs-type crystal structure. The results suggest that the magnetic domains and coercive force can be tuned by controlling the MnAs nanodisk size.
Error analysis of cross-shaped magnetic gradient full tensor measurement system
Authors: Xu Lei , Zhang Ning , Fang Liqing , Lin Pengfei , Chen Huadong , Chang Ming
Published: December 2020

The structural characteristics of the magnetic gradient full tensor measurement system are important factors affecting the accuracy of the magnetic gradient full tensor measurement. In order to analyze the measurement error of the cross-shaped magnetic gradient full tensor measurement system, the theoretical framework and structural configuration of the tensor system that is based on the magnetic dipole model are introduced. Four factors including the resolution, baseline length, target distance, and magnetic moment direction that cause measurement errors are simulated and analyzed. The simulation results show that the resolution, baseline length, and target distance have a great influence on the error of the measurement system. In contrast, the influence caused by the change in the magnetic moment direction is not significant. In a certain area, the resolution increases from 1 nT to 1 fT, and the error percentage of the tensor component Byy decreases the most, reaching 2.1370%. When designing the system structure, it is necessary to comprehensively consider the measurement purpose, design cost, measurement error, and other factors. It is important to select the fluxgate according to actual needs and coordinate the relationship between the baseline length and the measurement distance, which can be effective to decrease the error. The research conclusion can provide theoretical guidance for the design of the cross-shaped magnetic gradient full tensor measurement system.
Exploring cultural heritage through acoustic digital reconstructions
Authors: Katz Brian F. G. , Murphy Damian , Farina Angelo
Published: December 2020

Simulating the acoustics of destroyed or altered amphitheaters, cathedrals, and other architectural sites re-creates their sonic grandeur.
A bacterial cytolinker couples positioning of magnetic organelles to cell shape control
Authors: Pfeiffer Daniel , Toro-Nahuelpan Mauricio , Awal Ram Prasad , Müller Frank-Dietrich , Bramkamp Marc , Plitzko Jürgen M. , Schüler Dirk
Published: December 2020

Significance

The bacterial cytoskeleton is an intricate meshwork of filaments, fundamental for cell shape determination and subcellular organization. An elaborate example is found in magnetotactic bacteria, which employ a distinct cytoskeleton, the “magnetoskeleton,” to align magnetic nanoparticles (magnetosomes) for navigation within the geomagnetic field. Thus far, cytoskeletal determinants for cell shape in magnetotactic bacteria, and whether those are functionally linked to the magnetoskeleton, has remained unknown. Here, we describe the structural protein CcfM (curvature-inducing coiled-coil filament interacting with the magnetoskeleton), which functions as an interconnector (cytolinker) between the magnetoskeleton and cytoskeleton. CcfM not only controls cell curvature, but also formation of coherent cell-spanning magnetosome chains, enhancing magnetic navigation within environmental habitats.
Structure of the
Plasmodium
-interspersed repeat proteins of the malaria parasite
Authors: Harrison Thomas E. , Reid Adam J. , Cunningham Deirdre , Langhorne Jean , Higgins Matthew K.
Published: December 2020

Significance

The
Plasmodium
parasites that cause malaria replicate within blood cells of an infected host. These parasites send a small number of proteins to infected blood cell surfaces, allowing them to bind host molecules but also risking their detection by the host immune system. These proteins have diversified into large families, allowing the parasite to avoid detection by using antigenic variation. The most ubiquitous of these families is the
Plasmodium
-interspersed repeat (PIR) protein family. Here we present the structure of a PIR protein, revealing the architecture of its ectodomain and showing how it has diversified. Finally, we use structure-guided methods to understand which small variant surface antigen families are PIRs and to understand their evolution across malaria parasites.
Cellular proteostasis decline in human senescence
Authors: Sabath Niv , Levy-Adam Flonia , Younis Amal , Rozales Kinneret , Meller Anatoly , Hadar Shani , Soueid-Baumgarten Sharon , Shalgi Reut
Published: December 2020

Significance

Protein homeostasis (proteostasis), the balance between protein synthesis, folding, and degradation, is thought to deteriorate with age, and the prevalence of protein misfolding diseases (e.g., Alzheimer’s, Parkinson’s, etc.) with human aging is increased. However, while in worms this phenomenon has been well established, in humans, it remained unclear. Here, we show that proteostasis is declined in human cellular aging, termed cellular senescence. We found that while stress sensing is enhanced in senescent cells, and their response at the level of protein synthesis is intact, they fail to properly activate multiple programs required for stress adaptation at the level of gene transcription. Our findings support the notion that proteostasis decline may have major implications on human aging.
On three-dimensional rotating polymeric fiber jets with gravity effect
Authors: Riahi D N
Published: December 2020

We consider rotationally driven three-dimensional nonlinear polymeric fiber jets with the effect of gravity force. We implement an empirical viscosity model for the polymeric fluid of such flows to investigate the properties of the three-dimensional polymeric fiber jets generated by the imposed rotational forces. We apply theoretical and numerical techniques to determine the expressions for the leading order nonlinear solutions for the jet quantities such as radius, speed, stretching rate, strain rate and jet centerline versus arc length, and we calculate these quantities for different values of the parameters that represent the effects due to gravity, rotation, viscosity, surface tension and relaxation time. We find, in particular, that three-dimensionality of the jet system and the presence of the gravity force on the curved polymeric fiber jet can be significant in the sense that the values of the jet speed, strain rate, stretching rate and the centerline curvature are notably raised up and the jet radius size is notably dropped down and more so with increasing the arc length and the parameters due to gravity, rotation and the relaxation time of the polymeric jet.
Developing a predictive signature for two trial endpoints using the cross-validated risk scores method
Authors: Cherlin Svetlana , Wason James M S
Published: December 2020

The existing cross-validated risk scores (CVRS) design has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using high-dimensional data (such as genetic data). The design is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure. In some settings, it is desirable to consider the tradeoff between two outcomes, such as efficacy and toxicity, or cost and effectiveness. With this motivation, we extend the CVRS design (CVRS2) to consider two outcomes. The design employs bivariate risk scores that are divided into clusters. We assess the properties of the CVRS2 using simulated data and illustrate its application on a randomized psychiatry trial. We show that CVRS2 is able to reliably identify the sensitive group (the group for which the new treatment provides benefit on both outcomes) in the simulated data. We apply the CVRS2 design to a psychology clinical trial that had offender status and substance use status as two outcomes and collected a large number of baseline covariates. The CVRS2 design yields a significant treatment effect for both outcomes, while the CVRS approach identified a significant effect for the offender status only after prefiltering the covariates.
Seasonal variation of health in Asian elephants
Authors: Franco dos Santos Diogo J , Berger Vérane , Cristofari Robin , Htut Win , Nyein U Kyaw , Aung Htoo Htoo , Reichert Sophie , Lummaa Virpi
Published: December 2020

Long-lived species are often predicted to be buffered against seasonal variation: longevity means low annual mortality and reproductive rates and annual variability in climate may therefore have a smaller impact on population growth rates of long-lived species in comparison to short-lived ones. However, little is known of the physiological mechanisms underlying such patterns in long-lived species. In this study, we investigated seasonal variation in the health of Asian elephants living in a seasonal monsoon climate. We used two complementary methods: (i) global and (ii) trait-by-trait analyses of seasonal effects on 23 health parameters of 225 individually marked elephants with known age and reproductive and health history, with repeated measures per individual over a 26-month period. The global analysis highlighted the biggest differences in health between the hot and monsoon seasons. Our trait-specific analyses identified the physiological functions underlying such health variation in different ecological settings, including haematological, immunological, muscular, kidney and liver functions, as well as protein balance and electrolytes. Overall, the results suggest that even long-lived, large mammals may experience physiological changes in response to seasonal variation that in extreme circumstances can pose a significant health risk.
Diagnosis and management of male urinary tract infections: a need for new guidelines. Study from a French general practice electronic database
Authors: Soudais Benjamin , Lacroix-Hugues Virginie , Meunier François , Gillibert André , Darmon David , Schuers Matthieu
Published: December 2020

Background

The definition and the treatment of male urinary tract infections (UTIs) are imprecise. This study aims to determine the frequency of male UTIs in consultations of general practice, the diagnostic approach and the prescribed treatments.

Methods

We extracted the consultations of male patients, aged 18 years or more, during the period 2012–17 with the International Classification of Primary Care, version 2 codes for UTIs or associated symptoms from PRIMEGE/MEDISEPT databases of primary care. For eligible consultations in which all symptoms or codes were consistent with male UTIs, we identified patient history, prescribed treatments, antibiotic duration, clinical conditions, additional examinations and bacteriological results of urine culture.

Results

Our study included 610 consultations with 396 male patients (mean age 62.5 years). Male UTIs accounted for 0.097% of visits and 1.44 visits per physician per year. The UTIs most commonly identified were: undifferentiated (52%), prostatitis (36%), cystitis (8.5%) and pyelonephritis (3.5%). Fever was recorded in 14% of consultations. Urine dipstick test was done in 1.8% of consultations. Urine culture was positive for Escherichia coli in 50.4% of bacteriological tests. Fluoroquinolones were the most prescribed antibiotics (64.9%), followed by beta-lactams (17.4%), trimethoprim-sulfamethoxazole (11.9%) and nitrofurantoin (2.6%).

Conclusions

Male UTIs are rare in general practice and have different presentations. The definition of male UTIs needs to be specified by prospective studies. Diagnostic evidence of male cystitis may reduce the duration of antibiotic therapy and spare critical antibiotics.
Ultrastructural evidence for an unusual mode of ciliogenesis in mouse multiciliated epithelia
Authors: Narita Keishi , Takeda Sen
Published: December 2020

Multiciliogenesis is a cascading process for generating hundreds of motile cilia in single cells. In vertebrates, this process has been investigated in the ependyma of brain ventricles and the ciliated epithelia of the airway and oviduct. Although the early steps to amplify centrioles have been characterized in molecular detail, subsequent steps to establish multicilia have been relatively overlooked. Here, we focused on unusual cilia-related structures previously observed in wild-type mouse ependyma using transmission electron microscopy and analyzed their ultrastructural features and the frequency of their occurrence. In the ependyma, $\sim$5% of cilia existed as bundles; while the majority of the bundles were paired, bundles of more than three cilia were also found. Furthermore, apical protrusions harboring multiple sets of axonemes were occasionally observed (0–2 per section), suggesting an unusual mode of ciliogenesis. In trachea and oviduct epithelia, ciliary bundles were absent, but protrusions containing multiple axonemes were observed. At the base of such protrusions, certain axonemes were completely enwrapped by membranes, whereas others remained incompletely enwrapped. These data suggested that the late steps of multiciliogenesis might include a unique process underlying the development of cilia, which is distinct from the ciliogenesis of primary cilia.
Public health emergencies of international concern: a historic overview
Authors: Wilder-Smith Annelies , Osman Sarah
Published: December 2020

Rationale

The International Health Regulations (IHR) have been the governing framework for global health security since 2007. Declaring public health emergencies of international concern (PHEIC) is a cornerstone of the IHR. Here we review how PHEIC are formally declared, the diseases for which such declarations have been made from 2007 to 2020 and justifications for such declarations.

Key findings

Six events were declared PHEIC between 2007 and 2020: the 2009 H1N1 influenza pandemic, Ebola (West African outbreak 2013–2015, outbreak in Democratic Republic of Congo 2018–2020), poliomyelitis (2014 to present), Zika (2016) and COVID-19 (2020 to present). Poliomyelitis is the longest PHEIC. Zika was the first PHEIC for an arboviral disease. For several other emerging diseases a PHEIC was not declared despite the fact that the public health impact of the event was considered serious and associated with potential for international spread.

Recommendations

The binary nature of a PHEIC declaration is often not helpful for events where a tiered or graded approach is needed. The strength of PHEIC declarations is the ability to rapidly mobilize international coordination, streamline funding and accelerate the advancement of the development of vaccines, therapeutics and diagnostics under emergency use authorization. The ultimate purpose of such declaration is to catalyse timely evidence-based action, to limit the public health and societal impacts of emerging and re-emerging disease risks while preventing unwarranted travel and trade restrictions.
Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study
Authors: Van den Bosch Ines , Bouillon Thomas , Verhamme Peter , Vanassche Thomas , Jacquemin Marc , Coemans Maarten , Kuypers Dirk , Meijers Björn
Published: December 2020

Background

Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population.

Methods

We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day.

Results

Apixaban 5 mg resulted in higher area under the curve (AUC0–48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0–48 pre-dialysis were on average 48% (2.5 mg) and 26% (5 mg) lower than the AUC0–48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0–48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg group pre-dialysis (P = 0.02).

Conclusions

Our data suggest that exposure to apixaban in patients on maintenance haemodialysis is dependent not only on drug dose but also on timing of intake relative to the haemodialysis procedure.
Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease
Authors: Roodenrijs Nadia M T , van der Goes Marlies C , Welsing Paco M J , Tekstra Janneke , Lafeber Floris P J G , Jacobs Johannes W G , van Laar Jacob M
Published: December 2020

Objectives

Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease.

Methods

Consecutive RA patients were enrolled and categorized as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis.

Results

Fifty-two RA patients were classified as D2T and 100 as non-D2T. Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA [odds ratio (OR) 1.97 (95%CI 1.08–3.61)]. Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than in non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient’s and rheumatologist’s wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: (i) ‘non-adherent dissatisfied patients’; (ii) patients with ‘pain syndromes and obesity’; (iii) patients closest to the concept of ‘true refractory RA’.

Conclusions

This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.
The Moderating Effect of Age on the Association Between High-Performance Work Systems and Employee Performance in Different Work Roles
Authors: Pahos Nikolaos , Galanaki Eleanna , Van der Heijden Beatrice I J M , de Jong Jeroen
Published: December 2020

High performance work systems (HPWS) have been shown to associate with performance at diverse levels. In this article, we study the effects of employee age on the relationship between HPWS and employee performance. We use a role-based measurement of employee performance, which introduces five roles that an employee can hold within an organization, namely the roles of Job holder, Career seeker, Innovator, Team member, and Organization member. Integrating social exchange theory with lifespan theories (i.e., future time perspective and socio-emotional selectivity theory), we propose that HPWS have different associations with job roles for older employees. Using 342 pairs of supervisors and their subordinates, that are nested in 111 service organizations, multilevel analyses show that HPWS positively associate with employee performance in the Organization member role. Moreover, the relationships between HPWS and performance in the Job holder and the Career seeker roles are weaker for older than for younger employees. The results are discussed in the light of the challenges they pose for the management of an aging workforce.
Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality
Authors: Solcà Marco , Krishna Vibhor , Young Nicole , Deogaonkar Milind , Herbelin Bruno , Orepic Pavo , Mange Robin , Rognini Giulio , Serino Andrea , Rezai Ali , Blanke Olaf
Published: December 2020

Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, requiring sometimes the addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatiotemporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, 15 patients with severe chronic pain and an SCS implant underwent congruent SCS-VR (personalized visual feedback of the perceived SCS-induced paresthesia displayed on the patient's virtual body) and 2 control conditions (incongruent SCS-VR and VR alone). We demonstrate the efficacy of neuromodulation-enhanced VR for the treatment of chronic pain by showing that congruent SCS-VR reduced pain ratings on average by 44%. Spinal cord stimulation–VR analgesia was stronger than that in both control conditions (enabling stronger analgesic effects than incongruent SCS-VR analgesia or VR alone) and kept increasing over successive stimulations, revealing the selectivity and consistency of the observed effects. We also show that analgesia persists after congruent SCS-VR had stopped, indicating carry over effects and underlining its therapeutic potential. Linking latest VR technology with recent insights from the neuroscience of body perception and SCS neuromodulation, our personalized new SCS-VR platform highlights the impact of immersive digiceutical therapies for chronic pain.

Registration: clinicaltrials.gov, Identifier: NCT02970006.
Rallying All Resources
Authors: O'Glasser Avital Y. , Stroup Scott , Merkel Matthias J. , Lahti Elizabeth , Kubik Sharon , Vaughn Kristi , Reback Erin , Rumberger Ruth , Hayes Mariah , Backer Jennifer , Solani Tee , Halvorson Stephanie
Published: December 2020

Background:

The COVID-19 pandemic resulted in the need for hospitals to plan for a potential “surge” of COVID-19 patients.

Problem:

Prior to the onset of the COVID-19 pandemic, our hospital adult acute care capacity ranged 90% to 100%, and a potential hospital surge was projected for Oregon that would exceed existing capacity.

Approach:

A multidisciplinary team with stakeholders from nursing leadership, nursing units, nurse-led case management, and physicians from hospital medicine was convened to explore the conversion of an ambulatory surgical center to overflow patient acute care capacity.

Outcomes:

A protocol was rapidly created and implemented, ultimately transferring 12 patients to an ambulatory surgery unit.

Conclusions:

This project highlighted the ability for stakeholders and innovators to work together in an interprofessional, multidisciplinary way to rapidly create an overflow unit. While this innovation was designed to address COVID-19, the lessons learned can be applied to any other emerging infectious disease or acute care capacity crisis.
Technical Report: A New Method for Determining Image Distance for Stand Magnifiers
Authors: Lewerenz David , Hanson Kara , Hopkins Gregory
Published: December 2020

SIGNIFICANCE

Low vision rehabilitation clinicians must sometimes evaluate stand magnifiers to determine their true optical properties. A novel method is described for measuring the image distance of stand magnifiers.

PURPOSE

We describe a new method for determining the image distance of stand magnifiers, which has some advantages over previously described methods.

METHODS

Diverging light emerging from a stand magnifier is brought to a focus on the ceiling or other flat surface using convex lenses placed on the top of the stand magnifier lens. Knowing the power of this convex lens and the distance from the magnifier lens to the imaging surface, one can calculate the degree to which the emerging light is diverging and, from that, the image distance. Each author evaluated three stand magnifiers using this method and compared our results with each other and with the values for image distance published by the manufacturer.

RESULTS

Our method produced measurements that were consistent between three clinicians, with emerging divergence values differing by no more than 0.37 D and image distance differing by 0.6 to 3.1 cm for the three magnifiers evaluated. Our measured values also corresponded favorably with the published image distances listed in the manufacturer's catalog, deviating by a maximum of 3.7 cm and a mean of 1.3 cm. When the manufacturer's image distances were converted to dioptric divergence, our measurements varied by a maximum of 0.48 D and a mean of 0.17 D.

CONCLUSIONS

Our method provides an expedient and clinically accurate way to evaluate the divergence and image distance of a stand magnifier. Knowing the image distance is valuable by itself, but the divergence of the emerging light is also critical in determining the stand magnifier's enlargement ratio.
Use of Magnetic Resonance Imaging for Orthopedic Trauma and Infection in the Emergency Department
Authors: Huntley Joseph H. , Huntley Samuel R. , Greif Dylan N. , Marshall Danielle C. , Desai Sohil , Rodriguez Jose , Jose Jean
Published: December 2020

Conditions affecting the musculoskeletal system constitute a significant portion of medical emergencies in the United States, with traumatic injury and infection being two of the most common etiologies. Although physical examination and plain radiographs are often sufficient to guide diagnosis and treatment, there are myriad traumatic and infectious pathologies that are commonly missed or simply not detectable on plain radiographs. Advanced imaging is subsequently warranted for additional workup.

Magnetic resonance imaging (MRI) has become an increasingly used imaging modality for musculoskeletal complaints in the emergency department due to its superior visualization of soft tissues, focal edematous changes, and occult osseous insults often not visible on plain radiographs. Although multiple studies have evaluated its utility in the workup of emergency musculoskeletal complaints, there remains a dearth of literature examining the use of MRI for certain occult diagnoses.

Radiologists, emergency clinicians, and orthopedic surgeons must be knowledgeable of the indications for MRI in the emergency setting, as delayed diagnosis may contribute to increased morbidity and possibly mortality. This review summarizes the use of MRI in diagnoses relating to trauma or infection among patients presenting to the emergency department with a musculoskeletal complaint.
H3K4 trimethylation is required for postnatal pancreatic endocrine cell functional maturation
Authors: Campbell Stephanie A. , Bégin Jocelyn , McDonald Cassandra L. , Vanderkruk Ben , Stephan Tabea L. , Hoffman Brad G.
Published: December 2020

During pancreas development, endocrine progenitors differentiate into the islet-cell subtypes, which undergo further functional maturation in postnatal islet development. In islet β-cells, genes involved in glucose-stimulated insulin secretion are activated and glucose exposure increases the insulin response as β-cells mature. Here, we investigated the role of H3K4 trimethylation in endocrine cell differentiation and functional maturation by disrupting TrxG complex histone methyltransferase activity in mouse endocrine progenitors. In the embryo, genetic inactivation of TrxG componentDpy30in NEUROG3+ cells did not affect the number of endocrine progenitors or endocrine cell differentiation. H3K4 trimethylation was progressively lost in postnatal islets and the mice displayed elevated random and fasting glycemia, as well as impaired glucose tolerance by postnatal day 24. Although postnatal endocrine cell proportions were equivalent to controls, islet RNA-sequencing revealed a downregulation of genes involved in glucose-stimulated insulin secretion and an upregulation of immature β-cell genes. Comparison of histone modification enrichment profiles in NEUROG3+ endocrine progenitors and mature islets suggested that genes downregulated by loss of H3K4 trimethylation more frequently acquire active histone modifications during maturation. Taken together, these findings suggest that H3K4 trimethylation is required for the activation of genes involved in the functional maturation of pancreatic islet endocrine cells.
Deletion of INPP5E in the murine retina impairs axoneme formation and prevents photoreceptor disc morphogenesis
Authors: Sharif Ali S. , Gerstner Cecilia D. , Cady Martha A. , Arshavsky Vadim Y. , Mitchell Christina , Ying Guoxin , Frederick Jeanne M. , Baehr Wolfgang
Published: December 2020

INPP5E (pharbin) is a ubiquitously-expressed, farnesylated phosphatidylinositol polyphosphate 5’-phosphatase which modulates the phosphoinositide composition of membranes. INPP5E resides in primary cilia, and mutations or loss of INPP5E are associated with ciliary dysfunction. INPP5E missense mutations of the phosphatase catalytic domain cause Joubert syndrome in humans, a syndromic ciliopathy affecting multiple tissues including brain, liver, kidney and retina. We show that, differing from other primary cilia, INPP5E is present in the wildtype photoreceptor inner segment and absent in the outer segment--a modified primary cilium dedicated to phototransduction. We generatedInpp5eF/F;Six3Cre (in short,retInpp5e-/-) mice which exhibit a rapidly progressing rod-cone degeneration nearly completed by postnatal day 21 (P21) in the central retina. Mutant cone outer segments contain vesicles instead of discs as early as P8. While P10 mutant outer segments contain phototransduction and structural proteins, they do not form axonemes and fail to elaborate disc membranes. Connecting cilia ofretInpp5e-/-rods appear normal, although IFT-B/A particles accumulate at their distal ends suggesting disrupted intraflagellar transport. These results show that ablation of INPP5E does not impair the secretory pathway responsible for delivery of outer segment-specific proteins, but blocks axonemal extension and prevents disc morphogenesis.
Leveraging a surrogate outcome to improve inference on a partially missing target outcome
Authors: McCaw Zachary R. , Gaynor Sheila M. , Sun Ryan , Lin Xihong
Published: December 2020

Sample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray) for leveraging information from a correlated surrogate outcome (e.g. expression in blood) to improve inference on a partially missing target outcome (e.g. expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Sprayjointly models the target and surrogate outcomes within a bivariate regression framework. Unobserved values of either outcome are treated as missing data. We describe and implement an expectation conditional maximization algorithm for performing estimation in the presence of bilateral outcome missingness. Sprayestimates the same association parameter estimated by standard eQTL mapping and controls the type I error even when the target and surrogate outcomes are truly uncorrelated. We demonstrate analytically and empirically, using simulations and GTEx data, that in comparison with marginally modeling the target outcome, jointly modeling the target and surrogate outcomes increases estimation precision and improves power.
Association versus Prediction: the impact of cortical surface smoothing and parcellation on brain age
Authors: Zeighami Yashar , Evans Alan C.
Published: December 2020

Association and prediction studies of the brain target the biological consequences of aging and their impact on brain function. Such studies are conducted using different smoothing levels and parcellations at the preprocessing stage, on which their results are dependent. However, the impact of these parameters on the relationship between association values and prediction accuracy is not established. In this study, we used cortical thickness and its relationship with age to investigate how different smoothing and parcellation levels affect the detection of age-related brain correlates as well as brain age prediction accuracy. Our main measures were resel numbers - resolution elements - and age-related variance explained. Using these common measures enabled us to directly compare parcellation and smoothing effects in both association and prediction studies. In our sample of N=608 participants with age range 18-88, we evaluated age-related cortical thickness changes as well as brain age prediction. We found a negative relationship between prediction performance and correlation values for both parameters. Our results also quantify the relationship between delta age estimates obtained based on different processing parameters. Furthermore, with the direct comparison of the two approaches, we highlight the importance of correct choice of smoothing and parcellation parameters in each task, and how they can affect the results of the analysis in opposite directions.
Change point detection with multiple alternatives reveals parallel evaluation of the same stream of evidence along distinct timescales
Authors: Booras Alexa , Stevenson Tanner , McCormack Connor N. , Rhoads Marie E. , Hanks Timothy D.
Published: December 2020

In order to behave appropriately in a rapidly changing world, individuals must be able to detect when changes occur in that environment. However, at any given moment, there are a multitude of potential changes of behavioral significance that could occur. Here we investigate how knowledge about the space of possible changes affects human change point detection. We used a stochastic auditory change point detection task that allowed model-free and model-based characterization of the decision process people employ. We found that subjects can simultaneously apply distinct timescales of evidence evaluation to the same stream of evidence when there are multiple types of changes possible. Informative cues that specified the nature of the change led to improved accuracy for change point detection through mechanisms involving both the timescales of evidence evaluation and adjustments of decision bounds. These results establish three important capacities of information processing for decision making that any proposed neural mechanism of evidence evaluation must be able to support: the ability to simultaneously employ multiple timescales of evidence evaluation, the ability to rapidly adjust those timescales, and the ability to modify the amount of information required to make a decision in the context of flexible timescales.
Intein-assisted bisection mapping systematically splits proteins for Boolean logic and inducibility engineering
Authors: Ho Trevor Y. H. , Shao Alexander , Lu Zeyu , Savilahti Harri , Menolascina Filippo , Wang Lei , Dalchau Neil , Wang Baojun
Published: December 2020

Split inteins are powerful tools for seamless ligation of synthetic split proteins. Yet, their use remains limited because the already intricate split site identification problem is often complicated by the requirement of extein junction sequences. To address this, we augmented a mini-Mu transposon-based screening approach and devised the intein-assisted bisection mapping (IBM) method. IBM robustly revealed clusters of split sites on five proteins, converting them into AND or NAND logic gates. We further showed that the use of inteins expands functional sequence space for splitting a protein. We also demonstrated the utility of our approach over rational inference of split sites from secondary structure alignment of homologous proteins. Furthermore, the intein inserted at an identified site could be engineered by the transposon again to become partially chemically inducible, and to some extent enabled post-translational tuning on host protein function. Our work offers a generalizable and systematic route towards creating split protein-intein fusions and conditional inteins for protein activity control.