bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryopreserved platelets augment the inflammatory response: role of phosphatidylserine‐ and P‐selectin–mediated platelet phagocytosis in macrophages
Authors: Zhao Jingxiang , Xu Bocong , Chen Gan , Zhang Yuhua , Wang Quan , Zhao Lian , Zhou Hong
Published: February 2019

BACKGROUND

Cryopreservation in dimethyl sulfoxide and storage at −80 °C extends the shelf life of platelets to at least 2 years, allowing greater availability in rural and military areas. While cryopreserved platelets (CPPs) have been extensively characterized for coagulation and thrombin generation, reports on the mechanism of adverse reactions to CPPs transfusion are scarce. Here, we tested the hypothesis that CPPs facilitate phagocytosis by Kupffer cells and subsequently promote the inflammatory response in Kupffer cells.

STUDY DESIGN AND METHODS

P‐selectin expression, glycoprotein Ibα clustering and phosphatidylserine (PS) surface exposure on platelets stored at 22 °C, 4 °C and − 80 °C for 3 days were examined by flow cytometry. The phagocytosis of mepacrine‐labeled platelets coincubated with THP‐1 cells was examined by flow cytometry and confocal microscopy, and the release of cytokines from THP‐1 cells was measured by enzyme‐linked immunosorbent assay.

RESULTS

CPPs showed a marked enhancement of exposed PS but dramatically reduced glycoprotein Ibα expression and clustering compared with platelets stored at 4 °C. Activation of THP‐1 cells was stronger by CPPs than by platelets stored at 22 °C and 4 °C. CPP interference tests using annexin V and anti–P‐selectin showed that CPPs induced increases in PS‐ and P‐selectin–mediated phagocytosis, as well as secretion of the proinflammatory cytokine tumor necrosis factor‐α, and interleukins IL‐1β and IL‐6, but a decrease in transforming growth factor‐β production in THP‐1 cells. Surface‐exposed PS was more effective than P‐selectin for the activation of THP‐1 cells.

CONCLUSION

CPPs triggered PS and P‐selectin–mediated phagocytosis by macrophages and stimulated the inflammatory response of macrophages.
Nitrification via microorganism‐immobilized media using polyvinyl alcohol (PVA)
Authors: Shin Dong‐chul , Seo Jeong‐mi , Park Chul‐hwi
Published: February 2019

This study was conducted to investigate the nitrification of wastewater using polyvinyl alcohol (PVA) media immobilized with nitrifying bacteria. The microorganism‐immobilized media used in this study was prepared by mixing 10% (v/v) PVA, 6% (v/v) polyethylene glycol (PEG) and nitrifying microorganism culture solution. Analysis revealed that the nitrification rate when using the microorganism‐immobilized media increased to 49.1, 80.0 and 83.9% as the filling rate increased to 5, 15 and 25%, respectively. The mass transfer rate of the prepared microorganism‐immobilized media was estimated to be 37.69 mg/L·h maximum. The respiration rate was measured in order to compare with the microorganism‐immobilized media and the conventional biological treatment process of anaerobic‐anoxic‐oxic (A2O). Respiration time of sludge and the media were similar, but the respiration rate of the microorganism‐immobilized media (initial 20.8 mg O2/(L·h)) was higher than that of the activated sludge (initial 12.4 mg O2/(L·h)).
Relative Calabi–Yau structures
Authors: Brav Christopher , Dyckerhoff Tobias
Published: February 2019

We introduce relative noncommutative Calabi–Yau structures defined on functors of differential graded categories. Examples arise in various contexts such as topology, algebraic geometry, and representation theory. Our main result is a composition law for Calabi–Yau cospans generalizing the classical composition of cobordisms of oriented manifolds. As an application, we construct Calabi–Yau structures on topological Fukaya categories of framed punctured Riemann surfaces.
Farmers and Archaeologists: any shared interests? Best practice from the Dutch countryside
Authors: Groenendijk Henny A.
Published: February 2019

Farming in a country like the Netherlands, which has a limited surface area, high land value and critical customers, is like walking a tightrope: a farmer is always the scapegoat when it comes to the societal consequences of the job. Archaeologists, for example, have problems with modern cultivation techniques, because they can demonstrably harm archaeological sites, yet the farming community is reluctant to accede to the archaeologists' requests, since it has many more (larger) issues to overcome.

Predictive modelling as part of the development-led Dutch archaeology has not contributed to the desired mutual understanding. Yet there are signs of a growing willingness to listen to each other's needs, paralleled by developments in the environmental sector and the management of natural resources. Tentative projects to create a win-win situation for both farmers and archaeologists have been launched and even successfully carried out, but that is not enough. Archaeological heritage management requires permanent provisions, because the loss of information from the soil archive is irreversible. Attempts are being made to re-open the dialogue between farmers and archaeologists and bring about a more positive attitude on both sides. It is argued that severe actions are not effective in the Dutch polder.
Archaeоlogical Map of Bulgaria – Transport and Pipeline Infrastructure Projects
Authors: Kecheva Nadezhda
Published: February 2019

When the European Union began to finance transport and pipeline infrastructure constructions in Bulgaria, large-scale development-led archaeological projects emerged. After 2011, many 'polluter pays' projects were executed with the outlined workflow containing preliminary reports and fieldwork activities in accordance with Bulgarian legislation and a defined price list. As part of the process the national 'sites and monuments' archaeological information system 'Archaeological Map of Bulgaria' (AIS AKB) plays an important part as a source of archaeological data for the territory of Bulgaria. This centralised structure controls the quality of the archaeological fieldwork and data standardisation. The aim is to transform the 'sites and monuments' information system to an archaeological geographic information system (GIS) based on geospatial features, largely using an accumulation of standardised data.
Exact Solutions to H∞ and H2 Optimizations of Passive Resonant Shunt Circuit for Electromagnetic or Piezoelectric Shunt Damper
Authors: Ikegame Toru , Takagi Kentaro , Inoue Tsuyoshi
Published: February 2019

In this work, exact closed-form solutions are derived for optimizing the resonant shunt circuits of electromagnetic shunt dampers (EMSDs), which use an electromagnetic transducer, and piezoelectric shunt dampers (PZSDs), which use a piezoelectric element, shunted with an electric circuit. Modeling of the EMSD and PZSD is unified by nondimensional parameters. The optimization criteria selected for the EMSD and PZSD are H∞-norm minimization, H2-norm minimization, and exponential time-decay rate maximization. The aim of this study is to derive for the first time the exact solutions that have not previously been investigated, including cases that consider the inherent damping of the primary system. This paper comprehensively summarizes the exact solutions based on the optimization criteria together with approximated solutions obtained by the fixed-point method, which is commonly used to optimize the dynamic vibration absorber (DVA).
Discrete Energy-Conservation Properties in the Numerical Simulation of the Navier–Stokes Equations
Authors: Coppola Gennaro , Capuano Francesco , de Luca Luigi
Published: February 2019

Nonlinear convective terms pose the most critical issues when a numerical discretization of the Navier–Stokes equations is performed, especially at high Reynolds numbers. They are indeed responsible for a nonlinear instability arising from the amplification of aliasing errors that come from the evaluation of the products of two or more variables on a finite grid. The classical remedy to this difficulty has been the construction of difference schemes able to reproduce at a discrete level some of the fundamental symmetry properties of the Navier–Stokes equations. The invariant character of quadratic quantities such as global kinetic energy in inviscid incompressible flows is a particular symmetry, whose enforcement typically guarantees a sufficient control of aliasing errors that allows the fulfillment of long-time integration. In this paper, a survey of the most successful approaches developed in this field is presented. The incompressible and compressible cases are both covered, and treated separately, and the topics of spatial and temporal energy conservation are discussed. The theory and the ideas are exposed with full details in classical simplified numerical settings, and the extensions to more complex situations are also reviewed. The effectiveness of the illustrated approaches is documented by numerical simulations of canonical flows and by industrial flow computations taken from the literature.
Adjoint Methods as Design Tools in Thermoacoustics
Authors: Magri Luca
Published: February 2019

In a thermoacoustic system, such as a flame in a combustor, heat release oscillations couple with acoustic pressure oscillations. If the heat release is sufficiently in phase with the pressure, these oscillations can grow, sometimes with catastrophic consequences. Thermoacoustic instabilities are still one of the most challenging problems faced by gas turbine and rocket motor manufacturers. Thermoacoustic systems are characterized by many parameters to which the stability may be extremely sensitive. However, often only few oscillation modes are unstable. Existing techniques examine how a change in one parameter affects all (calculated) oscillation modes, whether unstable or not. Adjoint techniques turn this around: They accurately and cheaply compute how each oscillation mode is affected by changes in all parameters. In a system with a million parameters, they calculate gradients a million times faster than finite difference methods. This review paper provides: (i) the methodology and theory of stability and adjoint analysis in thermoacoustics, which is characterized by degenerate and nondegenerate nonlinear eigenvalue problems; (ii) physical insight in the thermoacoustic spectrum, and its exceptional points; (iii) practical applications of adjoint sensitivity analysis to passive control of existing oscillations, and prevention of oscillations with ad hoc design modifications; (iv) accurate and efficient algorithms to perform uncertainty quantification of the stability calculations; (v) adjoint-based methods for optimization to suppress instabilities by placing acoustic dampers, and prevent instabilities by design modifications in the combustor's geometry; (vi) a methodology to gain physical insight in the stability mechanisms of thermoacoustic instability (intrinsic sensitivity); and (vii) in nonlinear periodic oscillations, the prediction of the amplitude of limit cycles with weakly nonlinear analysis, and the theoretical framework to calculate the sensitivity to design parameters of limit cycles with adjoint Floquet analysis. To show the robustness and versatility of adjoint methods, examples of applications are provided for different acoustic and flame models, both in longitudinal and annular combustors, with deterministic and probabilistic approaches. The successful application of adjoint sensitivity analysis to thermoacoustics opens up new possibilities for physical understanding, control and optimization to design safer, quieter, and cleaner aero-engines. The versatile methods proposed can be applied to other multiphysical and multiscale problems, such as fluid–structure interaction, with virtually no conceptual modification.
Usefulness of contrast-enhanced ultrasound using perfluorobutanecontaining microbubbles as a planning for percutaneous biopsies of focal hepatic lesions: a prospective feasibility study
Authors: Lee Sang Min , Kim Jung Hoon , Yang Hyun Kyung , Kang Hyo-Jin , Han Joon Koo
Published: February 2019

Aims: To determine whether contrast-enhanced US using perfluorobutane-containing microbubbles (SEUS) would be helpful for planning a hepatic biopsy.Material and methods: This prospective study included 40 patients who planned to undergo hepatic biopsy for focal hepatic lesions. All patients underwent B-mode US followed by SEUS. The radiologist evaluated the number of detected lesions, presence of necrosis, conspicuity of target lesion and technical feasibility using 4-point scale. Technical failure and occurrence of change of the target were also assessed. Computer tomography (CT) or magnetic resonance (MR) images were the reference techniques. Results: The mean number of lesions detected on CT and MR images was 6.5±8.4. In 20 (50%) of 40 patients, more focal lesions were detected on SEUS. Targeted lesion was changed in sixpatients (15%) on SEUS. Mean number of detected lesions on SEUS was significantly higher comparing with B-US (5.1±6.2 vs. 2.8±3.8, p<0.001). Conspicuity of the targeted lesion was improved in 67.5% (27 of 40) on SEUS and significantly more visualized than B-US (3.6±0.8 vs. 2.8±0.9, p<0.001). In 7 more patients the necrosis within the lesion was visualized (17.5%) using SEUS. The technical feasibility on SEUS was significantly higher than B-US (2.3±1.0 vs. 3.3±0.9, p<0.001). Technical failure was observed in only one patient (2.5%).Conclusions: SEUS is a helpful technique for planning the hepatic biopsyin terms of detection, improving lesion conspicuity, tumor viable portion assessment and consequently higher operator confidence, compared with B-US.
Visual versus automatic ultrasound scoring of lung B-lines: reliability and consistency between systems
Authors: Short Jorge , Acebes Carlos , Rodriguez-de-Lema Guido , La Paglia Giuliana Maria Concetta , Pavón Maria , Sánchez-Pernaute Olga , Vazquez Julio Cesar , Romero-Bueno Fredeswinda , Garrido Jesús , Naredo Esperanza
Published: February 2019

Aims. To evaluate the agreement between a visual and an automatic counting system of lung B-lines by ultrasound (US) as well as to test the inter- and intra-observer reliability of both systems in patients with lung diseases.Material and methods. We included four patients with different lung conditions. Four ultrasonographers expert in lung US blindly, independently and consecutively performed, in two rounds, a US B-mode assessment of 8 lung intercostal spaces of each patient. Each US assessment consisted of a visual and an automatic counting of B-lines.Results. Agreement between visual and automatic counting of B-lines was good to excellent [intraclass correlation coefficient (ICC) 0.79-0.84, p<0.001]. Intra-observer reliability was good to excellent [ICC 0.62-0.99, p<0.001] except for one investigator in whom it was close to moderate for the automatic system [ICC 0.49, p<0.05]. Inter-observer reliability was excellent for both systems in both rounds [ICC 0.86-0.90, p<0.001].Conclusions. US automatic counting was consistent with US visual counting of lung B-lines, as performed by experts in the field. Both systems showed a high intra- and interobserver reliability.
A new species of the genus Saniosulus Summers (Acari: Eupalopsellidae) from Turkey
Authors: Doğan Salih , Bingül Meryem , Doğan Sibel
Published: February 2019

Diagnosis and description of a new mite species Saniosulus deliquus sp. nov. (Acari: Eupalopsellidae) are presented with illustrations based on specimens collected from Erzincan and Pülümür Valley, Turkey. An updated key to Saniosulus species is provided.
Purpose, Frequency, and Mode of Transport by Which Older Adults Leave Their Home—A Cross-Sectional Analysis
Authors: Mikolaizak A. Stefanie , Klenk Jochen , Rothenbacher Dietrich , Denkinger Michael D. , Rapp Kilian , _ _
Published: February 2019

Time spent out-of-home can increase physical activity (PA) levels. However, the association between the purpose for leaving home and the mode of transport on time out-of-home and PA are not straightforward. In a large sample of community-dwelling older adults (≥65 years), daily walking duration was measured prospectively over 1 week using body-fixed sensors and time-out-of-home questionnaires. Data from 1,277 participants yielded 6,500 full days for analysis. The following statistically significant associations were seen: public transport use increased the time spent out-of-home by 88 min and daily walking duration by 16 min. Social contacts or the use of a car increased the time out-of-home, but decreased PA. Shopping or “going by foot” decreased the time spent out-of-home by 19 and 62 min, respectively, while both increased the daily walking duration by 5 min. The association between time out-of-home and PA (daily walking duration) is strongly dependent on the activity and mode of transport.
Explaining Individual Differences in Fine Motor Performance and Learning in Older Adults: The Contribution of Muscle Strength and Cardiovascular Fitness
Authors: Hübner Lena , Vieluf Solveig , Godde Ben , Voelcker-Rehage Claudia
Published: February 2019

It remains controversial whether aging influences motor learning and whether physiological factors, such as local strength or fitness, are associated with fine motor performance and learning in older adults (OA). OA (n = 51) and young adults (YA,n = 31) performed a short-term motor learning session using a precision grip force modulation task. The rate of improvement of OA compared with YA was steeper with respect to performance variability and temporal precision. Both age groups showed positive transfer during an unpracticed variant of the force modulation task. Local muscle strength (pinch and grip strength) and high cardiovascular fitness positively predicted fine motor performance, whereas initial performance, muscle strength, and motor fitness (heterogeneous motor test battery) negatively predicted rate of improvement. Analyses indicated potentials, but also limits of plasticity for OA.
The Feasibility of Remotely Delivered Exercise Session in Adults With Alzheimer’s Disease and Their Caregivers
Authors: Ptomey Lauren T. , Vidoni Eric D. , Montenegro-Montenegro Esteban , Thompson Michael A. , Sherman Joseph R. , Gorczyca Anna M. , Greene Jerry L. , Washburn Richard A. , Donnelly Joseph E.
Published: February 2019

Adults with Alzheimer’s disease (AD) and their caregivers represent a segment of the population with low levels of moderate-intensity physical activity (MPA) and limited options for increasing MPA. The purpose of this study was to evaluate the feasibility of a group video conference approach for increasing MPA in adults with AD and their caregivers. Adults with AD and their caregivers attended 30-min group exercise sessions three times per week for 12 weeks. Exercise sessions and support sessions were delivered in their homes on a tablet computer over video conferencing software. Nine adults with AD/caregiver dyads enrolled, and seven completed the 12-week intervention. Adults with AD attended 77.3% of the group exercise sessions, and caregivers attended 79.2% of group exercise sessions. Weekly MPA increased in both adults with AD (49%) and caregivers (30%). Exercise delivered by group video conferencing is a feasible and potentially effective approach for increasing MPA in adults with AD and their caregivers.
Acute Effects of Gastrocnemius/Soleus Self-Myofascial Release Versus Dynamic Stretching on Closed-Chain Dorsiflexion
Authors: Somers Kimberly , Aune Dustin , Horten Anthony , Kim James , Rogers Julia
Published: February 2019

Context: Limited ankle dorsiflexion (DF) range of motion has been correlated with decreased flexibility of the gastrocnemius/soleus complex. Decreased ankle DF range of motion can lead to an increase in lower-extremity injuries, for example, acute ankle sprains, Achilles tendinopathy. Objective: The purpose of this study was to determine whether a single application of the intervention to the gastrocnemius/soleus complex via multidirectional self-myofascial release using a foam roller, multiplanar dynamic stretch performed in downward dog, or a combination of both techniques acutely improved ankle DF. Design: Subjects were assigned to groups via random card selection. Investigators provided verbal cues as needed to yield correct performance of interventions. Both interventions were performed twice for 1 minute using a dynamic walking rest of 30.48 m at a self-selected pace between interventions. Statistical analyses were completed using a 1-way analysis of variance, at α level ≤ .05. Setting: A convenience sample study. Participants: A total of 42 asymptomatic physical therapy students (18 females and 24 males) with mean age of 26.12 (4.03) years volunteered to participate. Interventions: Multidirectional self-myofascial release using a foam roller, multiplanar dynamic stretch performed in downward dog, or a combination of both techniques. Main Outcome Measures: Weight-bearing right ankle DF measurements were recorded in centimeters using a forward lunge technique (intraclass correlation coefficient = .98, .97, and .96). Results: Data analysis revealed no significant difference between the 3 groups in all pre–post measurements (P = .82). Mean (SD) measurements from pretest to posttest for myofascial release, dynamic stretching, and combination interventions were 0.479 (0.7) cm, 0.700 (0.7) cm, and 0.907 (1.4) cm, respectively. Conclusion: Until further studies are conducted, the selection of technique to increase ankle DF range of motion should be based on each individual patient’s ability, preference, and response to treatment.
Submaximal Cricket Fast Bowling Offers a Disproportionate Reduction in Loading Versus Performance: An Alternative Workload Intervention
Authors: Greig Matt , Child Benjamin
Published: February 2019

Context: Cricket fast bowlers are particularly susceptible to lumbar spine loading and injury. Quantitative analysis of technique typically involves laboratory-based biomechanical systems with limited ecological validity, whereas contemporary developments in global positioning satellite microtechnologies facilitate an on-field evaluation of loading. Objective: To quantify the influence of submaximal bowling from reduced approach lengths on performance and loading. Design: Repeated-measures, field-based design. Setting: Regulation cricket pitch. Participants: A total of 12 male cricket academy fast bowlers (18.7 [0.7] y), injury free with ≥3 years of competitive experience. Interventions: Each bowler wore 2 global positioning satellite units placed at C7 and L4 to measure triaxial acceleration (100 Hz). Bowlers completed an over (6 deliveries) from a randomized 3-, 6-, 9-, and 12-stride approach. Main Outcome Measures: Ball speed was recorded as the performance measure, with PlayerLoad in the anteroposterior, mediolateral, and vertical planes also calculated for each delivery length. Results: In ball speed, there was a significant main effect for delivery length (P = .02), with a 3-stride approach eliciting significantly less ball speed than a 9-stride (P = .03) or 12-stride (P = .002) approach. In loading, there was a significant main effect for delivery length (P < .001) in the anteroposterior, mediolateral, and vertical planes, with loading increasing linearly as a function of delivery strides. The 6-stride approach elicited a 44% reduction in loading, with a disproportionately small 3.5% decrease in performance. There was a significant main effect for global positioning satellite location (P ≤ .023) in all planes, with L4 eliciting greater loading than C7. Conclusions: A submaximal 6-stride approach yielded the optimum balance between reduced loading and performance inhibition. Reduced delivery length, therefore, offers an alternative to reduced overs in reducing loading in young bowlers and might also have practicable value in the rehabilitation of bowlers postinjury.
Operationally Conceptualizing Physical Literacy: Results of a Delphi Study
Authors: Shortt Chelsee A. , Webster Collin A. , Keegan Richard J. , Egan Cate A. , Brian Ali S.
Published: February 2019

Purpose: To operationally conceptualize physical literacy (PL) for application in the United States, using a modified Delphi approach, with PL academics.Methods: A sequential, mixed methods, modified Delphi research design was employed, consisting of three phases: (a) literature analysis, (b) Delphi Survey I (22 participants), and (c) Delphi Survey II (18 participants). Data were analyzed using qualitative coding and descriptive frequency statistics.Results: PL academics’ conceptions of PL suggested a multidimensional, noncontextual, personal, holistic learning process. Qualitative analysis generated two themes: (a) “PL is” and (b) “PL is not.” Quantitative results aligned with the qualitative findings. PL concepts that achieved unanimous agreement were (a) application of knowledge to physical activity (PA), (b) value of PA, (c) autonomous participation in PA, (d) enjoyment of PA, and (e) ability to participate in PA independently.Discussion/Conclusion: PL was operationalized as an autonomous application of movement, constructed by the individual’s conception of movement and response to adversity.
Measuring Perceived Transfer of Responsibility Learning From Physical Education: Initial Validation of the Transfer of Responsibility Questionnaire
Authors: Wright Paul M. , R. Richards K. Andrew , Jacobs Jennifer M. , Hemphill Michael A.
Published: February 2019

Purpose: Research indicates that physical education can be an effective setting for promoting positive values, attitudes, and behaviors that transfer to other settings. However, there is a lack of instrumentation to assess the cognitive and motivational aspects of the transfer process. Therefore, this study proposed and validated the Transfer of Responsibility Questionnaire (ToRQ).Methods: After instrument development and pilot testing, an initial version of the ToRQ was completed by 442 adolescents. Data analysis began with exploratory factor analysis followed by confirmatory factor analysis.Results: The exploratory factor analysis yielded a stable three-factor structure that measured the participants’ cognitive and motivational processes related to transfer. This factor structure was affirmed using confirmatory factor analysis, which also examined convergent and discriminant validity.Discussion/Conclusion: The model was a good fit for the data, and the ToRQ correlated positively with related scales from an existing life skill transfer survey. These analyses support the initial validation of the ToRQ.
Impact of a Physical Education Teacher’s Age on Elementary School Students’ Perceptions of Effectiveness and Learning
Authors: Pennington Colin G. , Curtner-Smith Matthew D. , Wind Stefanie A.
Published: February 2019

Purpose: To examine the impact of a physical education teacher’s age on students’ learning and perceptions of the teacher.Method: A total of 188 elementary students were randomly assigned to view one of two virtually identical filmed swimming lessons. In the young-appearance lesson, the teacher was youthful. In the middle-aged lesson, he had been aged by a theatrical make-up artist. Following the viewing of their assigned lesson, students completed an examination covering lesson content and a questionnaire about their perceptions of the teacher.Results: Inferential statistical tests indicated that students who watched the young-appearance lesson scored significantly higher on the examination and perceived the teacher to be significantly more likable, more competent, and a better role model than those who viewed the middle-aged lesson.Discussion: These findings could be interpreted as supporting either a sociological or psychological/developmental explanation for how and why students respond to and learn from older and younger physical educators.
In Vitro
Evaluation of the Drug Interaction Potential of Doravirine
Authors: Bleasby Kelly , Fillgrove Kerry L. , Houle Robert , Lu Bing , Palamanda Jairam , Newton Deborah J. , Lin Meihong , Chan Grace Hoyee , Sanchez Rosa I.
Published: February 2019

Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 infection.
In vitro
studies were conducted to assess the potential for drug interactions with doravirine via major drug-metabolizing enzymes and transporters.
A Xylose-Inducible Expression System and a CRISPR Interference Plasmid for Targeted Knockdown of Gene Expression in Clostridioides difficile
Authors: Müh Ute , Pannullo Anthony G. , Weiss David S. , Ellermeier Craig D.
Published: February 2019

Clostridioides difficile
has become the leading cause of hospital-acquired diarrhea in developed countries. A better understanding of the basic biology of this devastating pathogen might lead to novel approaches for preventing or treating
C. difficile
infections. Here we introduce new plasmid vectors that allow for titratable induction (P

xyl

) or knockdown (CRISPRi) of gene expression. The CRISPRi plasmid allows for easy depletion of target proteins in
C. difficile
. Besides bypassing the lengthy process of mutant construction, CRISPRi can be used to study the function of essential genes, which are particularly important targets for antibiotic development.
Manipulation of Aphid Behavior by a Persistent Plant Virus
Authors: Safari Maliheh , Ferrari Matthew J. , Roossinck Marilyn J.
Published: February 2019

This study demonstrates that a persistent plant virus can manipulate aphid behavior. This manipulation is in stark contrast to previously described effects of acute viruses on their hosts that facilitate their transmission. This study demonstrates a positive relationship between
Pepper cryptic virus 1
and jalapeño pepper (
Capsicum annuum
) plants wherein the virus protects the plants from the vector of acute viruses and reduces aphid herbivory. This work reveals an important implication of persistent plant viruses for pest and pathogen management in agriculture.
Implementation of a CRISPR-Based System for Gene Regulation in
Candida albicans
Authors: Román Elvira , Coman Ioana , Prieto Daniel , Alonso-Monge Rebeca , Pla Jesús
Published: February 2019

CRISPR technology is a new and efficient way to edit genomes, but it is also an appealing way to regulate gene expression. We have implemented CRISPR as a gene expression platform in
Candida albicans
using fusions between a Cas9 inactive enzyme and specific repressors or activators and demonstrated its functionality. This will allow future manipulation of complex virulence pathways in this important fungal pathogen.
Anticytomegalovirus Peptides Point to New Insights for CMV Entry Mechanisms and the Limitations of
In Vitro
Screenings
Authors: Jackson Joseph W. , Hancock Trevor J. , Dogra Pranay , Patel Ravi , Arav-Boger Ravit , Williams Angela D. , Kennel Stephen J. , Wall Jonathan S. , Sparer Tim E.
Published: February 2019

In the absence of an effective vaccine to prevent HCMV infections, alternative interventions must be developed. Prevention of viral entry into susceptible cells is an attractive alternative strategy. Here we report that heparan sulfate-binding peptides effectively inhibit entry into fibroblasts of
in vitro-
derived CMVs and partially inhibit
in vivo-
derived CMVs. This includes the inhibition of urine-derived HCMV (uCMV), which is highly resistant to antibody neutralization. While these antiviral peptides are highly effective at inhibiting cell-free virus, they do not inhibit MCMV cell-to-cell spread. This underscores the need to understand the mechanism of cell-to-cell spread and differences between
in vivo
-derived versus
in vitro-
derived CMV entry to effectively prevent CMV’s spread.
Modelling the allocation of paediatric intensive care retrieval teams in England and Wales
Authors: King Madeline , Ramnarayan Padmanabhan , Seaton Sarah E , Pagel Christina
Published: February 2019

Background

Following centralisation of UK paediatric intensive care units in 1997, specialist paediatric intensive care retrieval teams (PICRTs) were established to transport critically ill children from district general hospitals (DGHs). The current location and catchment area of PICRTs covering England and Wales are based on historical referral patterns. National quality standards specify that PICRTs should reach the patient bedside within 3 hours of accepting a referral.

Objective

To determine what proportion of demand for PICRT services in England and Wales can be reached within 3 hours and to explore the potential coverage impact of more stringent ‘time to bedside’ standards.

Methods

We used mathematical location–allocation methods to: (1) determine the optimal allocation of DGHs to current PICRT locations to minimise road journey time and calculated the proportion of demand reachable within 3 hours, 2 hours, 90 min, 75 min and 1 hour and (2) explore the impact of changing the number and location of PICRTs on demand coverage for the different time thresholds.

Results

For current (and optimal) location of 11 PICRTs, 98% (98%) of demand is reachable within 3 hours; 86% (91%) within 2 hours; 59% (69%) within 90 min; 33% (39%) within 75 min; and 20% (20%) within 1 hour. Five hospitals were not reachable within 3 hours. For the 3-hour standard, eight optimally located PICRT locations had similar coverage as the current 11 locations.

Conclusions

If new evidence supports reduction in the time to bedside standard, many more hospitals will not be adequately covered. Location–allocation optimisation is a powerful technique for supporting evidence-based service configuration.
Dexamethasone implant for non-infectious uveitis: is it cost-effective?
Authors: Squires Hazel , Bermejo Iñigo , Poku Edith N , Cooper Katy , Stevens John , Hamilton Jean , Wong Ruth , Denniston Alastair K , Pearce Ian , Quhill Fahd Mohammed
Published: February 2019

Background

Uveitis is inflammation inside the eye. The objective of this study is to assess the cost-effectiveness of a dexamethasone implant plus current practice (immunosuppressants and systemic corticosteroids) compared with current practice alone, in patients with non-infectious intermediate, posterior or pan-uveitis and to identify areas for future research.

Methods

A Markov model was built to estimate the costs and benefits of dexamethasone. Systematic reviews were performed to identify available relevant evidence. Quality of life data from the key randomised-controlled trial (HURON) was used to estimate the interventions’ effectiveness compared with the trial’s comparator arm (placebo plus limited current practice (LCP)). The analysis took a National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources.

Results

The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant compared with LCP is estimated as £19 509 per quality-adjusted life year (QALY) gained. The factors with the largest impact on the results were rate of blindness and relative proportion of blindness cases avoided by dexamethasone. Using plausible alternative assumptions, dexamethasone could be cost saving or it may be associated with an ICER of £56 329 per QALY gained compared with LCP.

Conclusions

Dexamethasone is estimated to be cost-effective using generally accepted UK thresholds. However, there is substantial uncertainty around these results due to scarcity of evidence. Future research on the following would help provide more reliable estimates: effectiveness of dexamethasone versus current practice (instead of LCP), with subgroup analyses for unilateral and bilateral uveitis, incidence of long-term blindness and effectiveness of dexamethasone in avoiding blindness.
Non-invasive diagnosis of retinoblastoma using cell-free DNA from aqueous humour
Authors: Gerrish Amy , Stone Edward , Clokie Samuel , Ainsworth John R , Jenkinson Helen , McCalla Maureen , Hitchcott Carol , Colmenero Isabel , Allen Stephanie , Parulekar Manoj , Cole Trevor
Published: February 2019

Retinoblastoma is the most common eye malignancy in childhood caused by mutations in the RB1 gene. Both alleles of the RB1 gene must be mutated for tumour development. The initial RB1 mutation may be constitutional germline or somatic (originating in one retinal cell only). Distinguishing between these alternative mechanisms is crucial, with wider implications for management of the patient and family members. Bilateral retinoblastoma is nearly always due to a constitutional mutation; however, approximately 15% of unilateral cases also carry a germline mutation, and identifying these cases is important. This can be achieved by identifying both mutation types in tumour tissue and excluding their presence in blood. Modern eye-saving chemotherapy treatment (systemic, intra-arterial and intravitreal) has resulted in fewer enucleations. As a result, tumour tissue required to identify sporadic RB1 mutation(s) is not always available. Modern intravitreal chemotherapeutic techniques for retinoblastoma involve aspiration of aqueous humour (AH), providing a novel sample source for analysis. By analysing cell-free DNA present in the AH fluid of eyes affected with retinoblastoma, we have developed a screening test capable of detecting somatic RB1 mutations that is comparable to current tests on enucleated tumour tissue. The results obtained with fluid from enucleated eyes were concordant with tumour tissue in all 10 cases analysed. In addition, AH analysis from two patients undergoing intravitreal chemotherapy successfully identified somatic variants in both cases. Our findings suggest that AH fluid is a promising source of tumour-derived DNA in retinoblastoma for analysis.
High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients
Authors: Sveaas Silje Halvorsen , Bilberg Annelie , Berg Inger Jorid , Provan Sella Arrestad , Rollefstad Silvia , Semb Anne Grete , Hagen Kåre Birger , Johansen Melissa Woll , Pedersen Elisabeth , Dagfinrud Hanne
Published: February 2019

Background

Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown.

Objective

To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA).

Method

Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0–10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study.

Results

97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: −0.6 [–0.8 to –0.3], p<0.001 and BASDAI: −1.2 [–1.8 to –0.7], p<0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health.

Conclusion

High intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients’ function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA.

Trial registration number

NCT02356874
.
Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)
Authors: Lo Winifred , Zhu Bin , Sabesan Arvind , Wu Ho-Hsiang , Powers Astin , Sorber Rebecca A , Ravichandran Sarangan , Chen Ina , McDuffie Lucas A , Quadri Humair S , Beane Joal D , Calzone Kathleen , Miettinen Markku M , Hewitt Stephen M , Koh Christopher , Heller Theo , Wacholder Sholom , Rudloff Udo
Published: February 2019

Introduction

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC.

Methods

One hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at <40 or breast cancer <50 years of age).

Results

Frequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants.

Conclusion

Type and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies.
Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients
Authors: Peng Xiang , Chen Jinchao , Wang Jiangyi , Peng Shuanghe , Liu Shengjie , Ma Kaifang , Zhou Jingcheng , Hong Baoan , Zhou Bowen , Zhang Jiufeng , Cai Lin , Gong Kan
Published: February 2019

Background

Historically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.

Methods

In this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.

Results

The mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.

Conclusion

This large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.
Short- and long-term effects of sodium chloride on strength and durability of coal fly ash stabilized with carbide lime
Authors: Consoli Nilo Cesar , Saldanha Rodrigo Beck , Scheuermann Filho Hugo Carlos
Published: February 2019

The research presented aims to quantify the influence of the curing period (t), dry unit weight (γd), lime amount (L), and the addition of sodium chloride (NaCl) on the short- and long-term behaviors of coal fly ash – carbide lime blends. Strength and wet–dry durability tests were carried out for differing values of porosity (η), L, and curing time (t) on mixtures that either contained small amounts of NaCl or contained none. Addition of NaCl to the mixtures resulted in significant increase in early strength gain when compared to specimens without NaCl, which demand longer curing periods to reach similar strength values. The addition of NaCl to coal fly ash – carbide lime blends reduced the accumulated loss of mass (ALM) after 12 wet–dry brushing cycles for specimens at early stages of curing (about 50% for 7 days). Equivalence in the unconfined compressive strength (qu) and ALM(after 12 wet–dry cycles) between the specimens with and without NaCl is achieved in the long term. Finally, a variance analysis performed regarding qu and ALM results yielded that the order of importance of the controllable factors changed from t, NaCl addition, γd, and L for strength to γd, t, NaCl addition, and L for ALM(after 12 wet–dry cycles).
Coupling phenomenon of anti-connected hybrid alignment nematics in thin cell: From submicron to nanoscale
Authors: Chen Sibo , Liu Xiaoting , Yu Huimin , Zhou Xuan , Zhang Zhidong
Published: February 2019

Within Landau–de Gennes theory, we modeled a system consisting of two anti-connected hybrid alignment nematics (HAN). Our numerical simulation results indicated the occurrence of four states denoted as I, II, III and IV. The states undergo a structure transition as a function of the cell gap d. For d [Formula: see text] d0, where d0is the maximum value for the structure transition to occur, state I and II are bistable, whereas state III and IV are metastable and quadruply degenerate. We found that d0= 15[Formula: see text], where [Formula: see text] is the biaxial characteristic coherence length. When d[Formula: see text] [Formula: see text] d [Formula: see text] d0, where d[Formula: see text] = 7[Formula: see text] and d[Formula: see text] is the critical cell gap for order reconstruction (OR), continuous inversion walls appear both in state III and IV. We first found that the structure transition from inversion walls to defect walls occurs with decreasing d from the submicron to nanoscale. During this process, quadruply degenerate states in state III and IV transformed into doubly degenerate states. Meanwhile, states I and II remained bistable. When d = d[Formula: see text], all states reached a new type of OR pattern with two biaxial walls cross-linked with each other by a novel approach; i.e., from defect walls to OR.
A reconfigurable scheme for realization of electro-optical logic gate based on silicon-graphene Mach–Zhender interferometer
Authors: Zivarian Hossein , Zarifkar Abbas
Published: February 2019

In this paper, we propose a reconfigurable scheme for implementation of an electro-optical logic gate by utilizing a Mach–Zehnder interferometer (MZI)-based structure. In order to achieve high performance and small footprint for the proposed logic gate, we have used a compact, broadband, low power and high speed MZI-based electro-optical switch which consists of a silicon-graphene slot waveguide as phase shifter in each arm of the MZI structure. Our design can perform electro-optical AND, OR and XOR logic functions in three different operational modes by using three electrical control signals. The functionality of the reconfigurable electro-optical logic gate is investigated with the help of eye diagram analysis for all three operational modes. Simulation results show that the proposed reconfigurable logic gate is able to work under at least 62.5 Gbit/s with high extinction ratio (ER) about 24.6 dB for transverse electric polarization mode at telecommunication wavelength of 1.55 [Formula: see text]m.