bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientation and flight behaviour identify the Soprano pipistrelle as a migratory bat species at the Baltic Sea coast
Authors: Lindecke O. , Elksne A. , Holland R. A. , Pētersons G. , Voigt C. C.
Published: March 2019

Migration routes of bats remain largely unknown, as previous orientation studies have been challenging even with newly developed techniques in tracking, genetic and stable isotope studies. However, a lack of knowledge about migrations poses problems for species conservation, especially in newly described species for which ecological information is not yet available. Here, we aimed to test flight orientation behaviour in the Soprano pipistrelle, Pipistrellus pygmaeus. This species has been described only 22 years ago but is now known to have a wide geographic distribution in Europe, yet virtually no information exists about seasonal movements of P. pygmaeus. In large parts of the continent, seasonal occurrence of P. pygmaeus matches with that of long‐distance migratory Nathusius' bats (Pipistrellus nathusii). To shed light on the migratory behaviour of both species, we investigated their orientation decisions at the Latvian Baltic Sea coast which is well‐known for summer bat migration along a north‐south axis. We developed an arena‐based assay designed to measure orientation of takeoffs. The arena was installed in the natural flight path of P. nathusii and P. pygmaeus, and after takeoff, bats chose the direction freely. We detected bearing fidelity between takeoff and departure flights, suggesting that bats used cues within the arena, putatively geomagnetic information, which allowed them to set a course prior to takeoff. Furthermore, our results show that P. pygmaeus orientates in a southerly, seasonally appropriate direction, similar to P. nathusii during ongoing migration. Therefore, our findings are consistent with true migratory behaviour of P. pygmaeus in the northern part of its range. Predicting flight directions of bats based on takeoff direction offers a simple test for orientation studies, and could further be used to test senses of bats under varying treatments, thereby facilitating a comparison of navigational skills across taxa, e.g., bats and birds.
Lactate and number of organ failures predict intensive care unit mortality in patients with acute‐on‐chronic liver failure
Authors: Cardoso Filipe S. , Abraldes Juan G. , Sy Eric , Ronco Juan J. , Bagulho Luís , Mcphail Mark J. , Karvellas Constantine J.
Published: March 2019

Background and Aims

Patients with acute‐on‐chronic liver failure (ACLF) have high mortality rates. Most prognostic scores were not developed for the intensive care unit (ICU) setting. We aimed to improve risk stratification for patients with ACLF in the ICU.

Methods

A training set with 240 patients with cirrhosis and organ failures (Chronic Liver Failure Sequential Organ Failure Assessment score [CLIF‐SOFA]) from Curry Cabral Hospital (Portugal) and University of Alberta Hospital (Canada) in 2010‐2016 was used to derive a prognostic model for ICU mortality. A validation set with 237 patients with cirrhosis and organ failures from Vancouver General Hospital (Canada) in 2000‐2011 was used to evaluate its performance.

Results

Amongst patients in the training set, ICU and hospital mortality rates were 39.2% and 54.6% respectively. Median lactate (4.4 vs 2.5 mmol/L) and number of organ failures (3 vs 2) on admission to ICU were associated with higher likelihood of ICU mortality (P < 0.001 for both). The lactate and organ failures predictive model (LacOF) was derived to predict ICU mortality: −2.420 + 0.072 × lactate + 0.569 × number of organ failures (area under‐the‐curve [AUC], 0.76). In the validation set, the LacOF model discriminative ability (AUC, 0.85) outperformed the CLIF‐SOFA (AUC, 0.79), Chronic Liver Failure Consortium Acute‐on‐Chronic Liver Failure (AUC, 0.73), Model for End‐stage Liver Disease score (AUC, 0.78) and Acute Physiology and Chronic Health Evaluation II scores (AUC, 0.74; P < 0.05 for all). The LacOF model calibration was good up to the 25% likelihood of ICU mortality.

Conclusions

In patients with ACLF, lactate and number of organ failures on admission to ICU are useful to predict ICU mortality. This early prognostic evaluation may help to better stratify the risk of ICU mortality and thus optimize organ support strategies.
Chromosome polymorphisms track trans‐Atlantic divergence and secondary contact in Atlantic salmon
Authors: Lehnert Sarah J. , Bentzen Paul , Kess Tony , Lien Sigbjørn , Horne John B. , Clément Marie , Bradbury Ian R.
Published: March 2019

Pleistocene glaciations drove repeated range contractions and expansions shaping contemporary intraspecific diversity. Atlantic salmon (Salmo salar) in the western and eastern Atlantic diverged >600,000 years before present, with the two lineages isolated in different southern refugia during glacial maxima, driving trans‐Atlantic genomic and karyotypic divergence. Here, we investigate the genomic consequences of glacial isolation and trans‐Atlantic secondary contact using 108,870 single nucleotide polymorphisms genotyped in 80 North American and European populations. Throughout North America, we identified extensive interindividual variation and discrete linkage blocks within and between chromosomes with known trans‐Atlantic differences in rearrangements: Ssa01/Ssa23 translocation and Ssa08/Ssa29 fusion. Spatial genetic analyses suggest independence of rearrangements, with Ssa01/Ssa23 showing high European introgression (>50%) in northern populations indicative of post‐glacial trans‐Atlantic secondary contact, contrasting with low European ancestry genome‐wide (3%). Ssa08/Ssa29 showed greater intrapopulation diversity, suggesting a derived chromosome fusion polymorphism that evolved within North America. Evidence of potential selection on both genomic regions suggests that the adaptive role of rearrangements warrants further investigation in Atlantic salmon. Our study highlights how Pleistocene glaciations can influence large‐scale intraspecific variation in genomic architecture of northern species.
Deletion of Robo4 prevents high‐fat diet‐induced adipose artery and systemic metabolic dysfunction
Authors: Phuong Tam T. T. , Walker Ashley E. , Henson Grant D. , Machin Daniel R. , Li Dean Y. , Donato Anthony J. , Lesniewski Lisa A.
Published: March 2019

Objective

Accumulating evidence suggests the vascular endothelium plays a fundamental role in the pathophysiology of obesity by regulating the functional status of white adipose and systemic metabolism. Robo4 is expressed specifically in endothelial cells and increases vascular stability and inhibits angiogenesis. We sought to determine the role of Robo4 in modulating cardiometabolic function in response to high‐fat feeding.

Methods

We examined exercise capacity, glucose tolerance, and white adipose tissue artery gene expression, endothelium‐dependent dilation (EDD), and angiogenesis in wild type and Robo4 knockout (KO) mice fed normal chow (NC) or a high‐fat diet (HFD).

Results

We found Robo4 deletion enhances exercise capacity in NC‐fed mice and HFD markedly increased the expression of the Robo4 ligand, Slit2, in white adipose tissue. Deletion of Robo4 increased angiogenesis in white adipose tissue and protected against HFD‐induced impairments in white adipose artery vasodilation and glucose intolerance.

Conclusions

We demonstrate a novel functional role for Robo4 in endothelial cell function and metabolic homeostasis in white adipose tissue, with Robo4 deletion protecting against endothelial and metabolic dysfunction associated with a HFD. Our findings suggest that Robo4‐dependent signaling pathways may be a novel target in anti‐obesity therapy.
A two‐component regulatory system VfmIH modulates multiple virulence traits in Dickeya zeae
Authors: Lv Mingfa , Hu Ming , Li Peng , Jiang Zide , Zhang Lian‐Hui , Zhou Jianuan
Published: March 2019

Bacterial pathogen Dickeya zeae strain EC1 produces antibiotics‐like phytotoxins called zeamines, which are major virulence determinants encoded by the zms gene cluster. In this study, we identified a zeamine‐deficient mutant with a Tn5 insertion in a gene designated as vfmI encoding a two‐component system (TCS) sensor histidine kinase (HK), which is accompanied by vfmH encoding a response regulator (RR) at the same genetic locus. Domain analysis shows this TCS is analogous to the VfmIH of D. dadantii, with typical characteristics of sensor HK and RR, respectively, and sharing the same operon. Deletion of either vfmI or vfmH resulted in decreased production of zeamines and cell wall degrading enzymes (CWDEs), and alleviated virulence on rice seeds and potato tubers. In D. dadantii 3937, VfmH was shown to bind to the promoters of vfmA and vfmE, while in D. zeae EC1, VfmH could bind to the promoters of vfmA, vfmE and vfmF. RNA‐seq analysis of strain EC1 and its vfmH mutant also showed that the TCS positively regulated a range of virulence genes, including zms, T1SS, T2SS, T3SS, T6SS, flagellar and CWDE genes.
Calcineurin responsive zinc‐finger‐1 binds to a unique promoter sequence to upregulate neuronal calcium sensor‐1, whose interaction with MID‐1 increases tolerance to calcium stress in Neurospora crassa
Authors: Gohain Dibakar , Tamuli Ranjan
Published: March 2019

We studied the molecular mechanism of neuronal calcium sensor‐1 (NCS‐1) signaling pathway for tolerance to Ca2+ stress in Neurospora crassa. Increasing concentration of Ca2+ increased the expression of ncs‐1; however, the calcineurin inhibitor FK506 severely reduced ncs‐1 mRNA transcript levels. Chromatin immunoprecipitation (ChIP) studies revealed that the transcription factor calcineurin responsive zinc finger‐1 (CRZ‐1) binds to the ncs‐1 promoter, and CRZ‐1 binding upregulated ncs‐1 expression under high Ca2+ concentrations. These results suggested the regulation of NCS‐1 function through calcineurin‐ CRZ‐1 signaling pathway. Furthermore, the electrophoretic mobility shift assay (EMSA) revealed that the CRZ‐1 binds specifically to an 8 bp sequence 5ʹ‐CCTTCACA‐3ʹ in the ncs‐1 promoter 216 bp upstream of the ATG start codon. We also showed that NCS‐1 binds to the Ca2+ permeable channel MID‐1 for tolerance to Ca2+ stress. Therefore, CRZ‐1 binds to a unique sequence in the ncs‐1 promoter, causing upregulation of NCS‐1 that binds to MID‐1 for tolerance to Ca2+ stress.
Comparison of genotyping methods for Cunninghamella bertholletiae
Authors: Verhasselt Hedda Luise , Radke Julia , Schmidt Dirk , Killengray David , Scharmann Ulrike , Rickerts Volker , Hansen Wiebke , Seidel Danila , Falces‐Romero Iker , Buer Jan , Rath Peter‐Michael , Steinmann Joerg
Published: March 2019

Background

Invasive fungal infections caused by filamentous fungi of the order Mucorales are serious complications in immunocompromised patients and often associated with fatal outcome. As a member of this order, Cunninghamella bertholletiae is a saprophytic fungus with naturally exhibited high minimum inhibitory concentrations against common antifungal drugs and with the potential for outbreaks in clinical settings.

Objectives and methods

In a proof‐of‐principle study, we evaluated the performance of microsatellite markers for the discrimination of thirteen C. bertholletiae isolates from various sources in comparison with a repetitive sequence‐based PCR (rep‐PCR) and random amplification of polymorphic DNA (RAPD). Based on the higher discriminatory power of the microsatellite PCR with five separate primer pairs (Simpson's index of 1 vs 0 [RAPD] and 0 [rep‐PCR]), the novel method was applied to eight additional isolates, including four well‐characterised isolates from a cluster of infections in a next step.

Results

In total, microsatellite PCR identified 21 separate genotypes. A probable epidemiological association of the cluster isolates could be demonstrated by microsatellite genotyping.

Conclusion

In conclusion, our findings demonstrate the value of microsatellite PCR in genotyping Cunninghamella bertholletiae and its potential for future applications with other species of the order Mucorales.
Algae−bacteria interactions that balance the planktonic microbiome
Authors: Cirri Emilio , Pohnert Georg
Published: March 2019

Phytoplankton communities within the photic zones of the oceans and lakes are characterised by highly complex assemblages of unicellular microalgae and associated bacteria. The interconnected evolutionary history of algae and bacteria allowed the formation of a wide spectrum of associations defined by orchestrated nutrient exchange, mutual support with growth factors, quorum sensing mediation, and episodic killing of the partners to obtain more resources. In this review, we discuss how these cross‐kingdom interactions shape plankton communities that undergo annual, seasonal switching between alternative states with balanced multispecies consortia. We illustrate how these microscopic interactions can have consequences that scale up to influence global element cycling.
Evolutionary history of the buildup and breakdown of the heterostylous syndrome in Plumbaginaceae
Authors: Costa Joana , Torices Rubén , Barrett Spencer C. H.
Published: March 2019

The evolutionary pathways leading to the heterostylous syndrome are not well understood, and models concerning the origins of distyly differ in the order in which reciprocal herkogamy and self‐incompatibility evolve. We investigated the evolution and breakdown of distyly in Plumbaginaceae, a family with considerable diversity of floral traits and reproductive systems.

Using Bayesian Markov chain Monte Carlo analyses and stochastic character mapping, we examined the evolutionary assembly and breakdown of the heterostylous syndrome based on a well‐resolved phylogeny of 121 species of Plumbaginaceae and six outgroup taxa using five nuclear and plastid gene regions. We used the distribution of reproductive traits and reconstructed ancestral characters across phylogenies to evaluate competing models for the evolution of distyly.

The most likely common ancestor of Plumbaginaceae was self‐incompatible and monomorphic for sex‐organ arrangement and pollen‐stigma characters. Character state reconstructions indicated that reciprocal herkogamy evolved at least three times and that shifts to selfing and apomixis occurred on multiple occasions.

Our results provide comparative support for the early ideas of H. G. Baker on evolutionary pathways in Plumbaginaceae, and the more recent selfing avoidance model by D. & B. Charlesworth in which distyly evolves from self‐incompatible ancestors.
European Society of Pediatric Nephrology survey on current practice regarding recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation
Authors: Bouts Antonia , Veltkamp Floor , Tönshoff Burkhard , Vivarelli Marina ,   Members of the Working Group “Transplantation”, “Idiopathic Nephrotic Syndrome” of the European Society of Pediatric Nephrology
Published: March 2019

Introduction

Primary FSGS is an important cause of ESRD in children. FSGS recurrence after kidney transplantation is associated with early graft loss. No guidelines for treatment of FSGS recurrence exist. We conducted a survey to gain insight into variation of treatment between centers.

Methods

A survey was sent to all members of the ESPN on behalf of the “Renal Transplantation” and “Idiopathic Nephrotic Syndrome” working groups.

Results

Fifty‐nine nephrologists from 31 countries responded, reporting 807 FSGS patients, with 241 (30%) FSGS recurrences after transplantation. Recurrence varied from 0% to 100% between respondents. Native nephrectomy before or during transplantation was performed, respectively, always (37%), never (39%), or on clinical indication (17%). Half of the respondents started preventive treatment before transplantation, using PF (n = 10); R (n = 4); PF or IA, plus R (n = 9); cyclosporine (n = 2); or unknown (n = 4). Immunosuppressive therapy for patients without known mutations consisted of a combination of steroids, tacrolimus/cyclosporine, and MMF, with or without IL‐2R‐blockade in, respectively, 61% and 86% of the respondents. Sixty‐three percent applied a similar regimen to patients with known mutations. FSGS recurrence was treated with PF or IA, plus R by 66% of respondents; 54% observed no response. Complete remission in >50% of patients was reported by 41% of the respondents.

Discussion

FSGS recurrence after transplantation is common, but varies greatly between centers. We found great variability in preventive and therapeutic treatment regimens. Future research should focus on predisposing factors, including biopsy findings and genetic mutations, and standardized treatment.
Structural brain differences predict early traumatic memory processing
Authors: Gvozdanovic Geraldine , Stämpfli Philipp , Seifritz Erich , Rasch Björn
Published: March 2019

Intrusive memories are a key symptom of post‐traumatic stress disorder (PTSD). They emerge early after trauma exposure and are predictive for PTSD development. There is a high relevance in evaluating the neurobiological mechanisms of early stages of intrusive symptom development to provide a further understanding of PTSD. In the present study, we explore structural differences in healthy young female subjects preceding experimental trauma exposure and their relationship to early intrusive memory development using a traumatic film paradigm. With voxel‐based morphometry, we demonstrate that smaller insular volume was associated with an increased number of early intrusive film memories. Moreover, larger lingual gyrus/cerebellar and inferior frontal gyrus/precentral gyrus volumes were also related to an increased number of early intrusive film memories. Our results identify unique brain areas associated with early experimental trauma memory processing and highlight the necessity of evaluating early symptom stages relevant for personalized PTSD prevention and treatment.
Noninvasive fetal RHD genotyping to guide targeted anti‐D prophylaxis–an external quality assessment workshop
Authors: Clausen Frederik Banch , Barrett Angela Natalie ,   The Noninvasive Fetal RHD Genotyping EQA2017 Working Group
Published: March 2019

Background and Objectives

Fetal RHD genotyping of cell‐free fetal DNA from RhD‐negative pregnant women can be used to guide targeted antenatal and postnatal anti‐D prophylaxis for the prevention of RhD immunization. To assure the quality of clinical testing, we conducted an external quality assessment workshop with the participation of 28 laboratories.

Materials and Methods

Aliquots of pooled maternal plasma were sent to each laboratory. One sample was positive, and the second sample was negative for fetal RHD, verified by pre‐workshop testing using quantitative real‐time PCR (qPCR) analysis of RHD exons 4, 5, 7 and 10. Plasma samples were shipped at room temperature. A reporting scheme was supplied for data collection, including questions regarding the methodological setup, results and clinical recommendations. Different methodological approaches were used, all employing qPCR with a total of eight different combinations of RHD exon targets. The samples were tested blindly.

Results

Fetal RHD genotyping was performed with no false‐negative and no false‐positive results. One inconclusive result was reported for the RHD‐positive sample, and four inconclusive results were reported for the RHD‐negative sample. All clinical conclusions were satisfactory.

Conclusion

This external quality assessment workshop demonstrates that despite the different approaches taken to perform the clinical assays, fetal RHD genotyping is a reliable laboratory assay to guide targeted use of Rh prophylaxis in a clinical setting.
A tractable, simplified ex vivo human skin model of wound infection
Authors: Yoon Daniel J. , Fregoso Daniel R. , Nguyen Duc , Chen Vivien , Strbo Natasa , Fuentes Jaime J. , Tomic‐Canic Marjana , Crawford Robert , Pastar Irena , Isseroff R. Rivkah
Published: March 2019

The prevalence of infection in chronic wounds is well documented in the literature but not optimally studied due to the drawbacks of current methodologies. Here, we describe a tractable and simplified ex vivo human skin model of infection that addresses the critical drawbacks of high costs and limited translatability. Wounds were generated from excised abdominal skin from cosmetic procedures and cultured, inoculated with Staphylococcus aureus strain UAMS‐1, or under aseptic conditions. After three days, the infected wounds exhibited biofilm formation and significantly impaired reepithelialization compared to the control. Additionally, promigratory and proreparative genes were significantly downregulated, while proinflammatory genes were significantly upregulated, demonstrating molecular characterizations of impaired healing as in chronic wounds. This model allows for a simplified and versatile tool for the study of wound infection and subsequent development of novel therapies.
The desirable donor pig to eliminate all xenoreactive antigens
Authors: Ladowski Joseph , Martens Greg , Estrada Jose , Tector Matthew , Tector Joseph
Published: March 2019

The humoral barrier has been the limiting factor in moving xenotransplantation towards the clinic. Improvements in somatic cell nuclear transfer and genome editing, particularly CRISPR‐Cas9, have made it possible to create pigs with multiple glycan xenoantigen deletions for the purposes of reducing xenoreactive antibody binding to the xenografted organ. Recent studies have also considered the aetiology and existence of antibodies directed at the swine leucocyte antigen (SLA) complex, and potential genetic engineering strategies to avoid these antibodies. Evaluation of xenoreactive antibody binding is very important for the advancement of xenotransplantation, because if patients do not have any detectable xenoreactive antibody, then it is reasonable to expect that cellular rejection and not antibody‐mediated rejection (AMR) will be the next hurdle to clinical application.
An experimental analysis on the performance of single mode-multimode-single mode and multimode- single mode-multimode fiber optic sensor
Authors: Abdul Razak Hanim
Published: March 2019

A cost effective and simple fabrication process for Mach Zehnder Interferometer (MZI) fiber based sensor has been proposed based on single mode-multimode-single mode structure and multimode-single mode-multimode. These proposed structures employed a standard fusion arc splicing by varying the length of sensing region instead of the structures. This sensor has been experimentally demonstrated for three different concentration of solutions such as water, 1mol sucrose solution and oil with the refractive index of 1.333, 1.384 and 1.464 respectively. Furthermore, the intention of this experiment is to determine which structure that provides superior performance in terms of the sensitivity of the device. The operating wavelength of different structures corresponds to the different refractive index. It is observed that the shifting response was influenced by the length of the sensing-area and the best sensitivity achieved for is -10.45nm/RIU.
Grid-Induced Numerical Errors for Shear Stresses and Essential Flow Variables in a Ventricular Assist Device: Crucial for Blood Damage Prediction?
Authors: Konnigk Lucas , Torner Benjamin , Hallier Sebastian , Witte Matthias , Wurm Frank-Hendrik
Published: March 2019

Adverse events due to flow-induced blood damage remain a serious problem for blood pumps as cardiac support systems. The numerical prediction of blood damage via computational fluid dynamics (CFD) is a helpful tool for the design and optimization of reliable pumps. Blood damage prediction models primarily are based on the acting shear stresses, which are calculated by solving the Navier–Stokes equations on computational grids. The purpose of this paper is to analyze the influence of the spatial discretization and the associated discretization error on the shear stress calculation in a blood pump in comparison to other important flow quantities like the pressure head of the pump. Therefore, CFD analysis using seven unsteady Reynolds-averaged Navier–Stokes (URANS) simulations was performed. Two simple stress calculation indicators were applied to estimate the influence of the discretization on the results using an approach to calculate numerical uncertainties, which indicates discretization errors. For the finest grid with 19 × 106 elements, numerical uncertainties up to 20% for shear stresses were determined, while the pressure heads show smaller uncertainties with a maximum of 4.8%. No grid-independent solution for velocity gradient-dependent variables could be obtained on a grid size that is comparable to mesh sizes in state-of-the-art blood pump studies. It can be concluded that the grid size has a major influence on the shear stress calculation, and therefore, the potential blood damage prediction, and that the quantification of this error should always be taken into account.
Dynamical Analysis of Coupled Bidirectional FitzHugh–Nagumo Neuronal Networks With Multiple Delays
Authors: Mao Xiaochen , Zhou Xiangyu , Shi Tiantian , Qiao Lei
Published: March 2019

Coupled neuronal networks have received considerable attention due to their important and extensive applications in science and engineering. This paper focuses on the nonlinear dynamics of delay-coupled bidirectional FitzHugh–Nagumo (FHN) neuronal networks through theoretical analysis, numerical computations, and circuit simulations. A variety of interesting dynamical behaviors of the network are explored, such as the coexistence of nontrivial equilibria and periodic solutions, different patterns of coexisting attractors, and even chaotic motions. An electronic circuit is designed and performed to validate the facticity of the complicated behaviors, such as multistability and chaotic attractors. It is shown that the circuit simulations reach an agreement with the obtained results.
Prediction of Fracture Failure of Steel Pipes With Sharp Corrosion Pits Using Time-Dependent Reliability Method With Lognormal Process
Authors: Fu Guoyang , Yang Wei , Deng Wenni , Li Chun-Qing , Setunge Sujeeva
Published: March 2019

This paper presents a reliability-based methodology for assessing fracture failures of steel pipes with sharp corrosion pits. Based on newly developed models of elastic fracture toughness, the simple criterion of stress intensity factor (SIF) is used to establish the limit state functions for pipes with sharp corrosion pits in the longitudinal and circumferential directions. A stochastic model of load effect is developed and a time-dependent reliability method based on first passage probability for nonstationary lognormal processes is employed to quantify the probability of failure and predict the remaining service life. After applying the methodology to a case study, sensitivity analysis is carried out to identify the most influential variables on the probability of failure. It is found in the paper that the correlation coefficient has a considerable effect on probability of failure of steel pipes with sharp corrosion pits and that the larger the mode I fracture toughness is, the smaller the probability of pipe failure is.
Optimization and Standardization of Flanged and Flued Expansion Joint Design
Authors: Chikhaliya Kamlesh M. , Patel Bhaveshkumar P.
Published: March 2019

Flanged and flued type expansion joint (thick wall expansion bellow) used as an integral part of many shell and tube heat exchanger where process conditions produce differential expansion between shell and tubes. It provides flexibility for thermal expansion and also functions as a pressure retaining part. Design of expansion joints is usually based on trial and error method in which initial geometry must be assumed, and accordingly maximum stresses and spring rate are be calculated. Inadequate selection of geometry leads to higher tubesheet and bellow thickness, which increases cost of equipment. This paper presents standardization and optimum design approach of flange and flued expansion bellow fulfilling ASME VIII-1 and TEMA standard requirement. Methodology to define expansion bellow geometry is developed, and geometry dimensions are tabulated for expansion bellow diameter from 300 to 2000 mm and thickness from 6 to 30 mm. Each defined geometry is analyzed using finite element method, and maximum von Mises stresses are calculated for bellow axial displacement from 0.5 to 1.5 mm and internal pressure from 0.1 to 6.5 MPa. Spring rate is also calculated for each defined geometry for consideration in tubesheet calculation. Accordingly, optimum design methodology is developed, tested, and compared with existing design. Results depicted that proposed standardization approach and design methodology will optimize expansion bellow and tubesheet thickness and will also save considerable time in finalization of heat exchanger design.
Programmable Multistable Mechanisms for Safe Surgical Puncturing
Authors: Zanaty Mohamed , Fussinger Thomas , Rogg Arno , Lovera Andrea , Lambelet David , Vardi Ilan , Wolfensberger Thomas J. , Baur Charles , Henein Simon
Published: March 2019

We present novel medical devices for safe surgical puncturing, in particular a cannula for the treatment of retinal vein occlusion (RVO). This passive mechanical device has an adjustable stroke and exerts a puncturing force independent of operator applied displacement. The innovative feature of this tool is that puncturing stroke is decoupled from operator input thereby minimizing the possibility of overpuncturing. This is achieved using our concept of stability programming, where the user modifies the mechanism strain energy as opposed to imposing direct displacement which is the case for standard bistable mechanisms. Ultra-fast laser three-dimensional (3D) printing is used to manufacture the needle in glass. A microfluidic channel is integrated into the needle tip for drug injection. Numerical simulations and experimental measurements validate the mechanical stability behavior of the puncture mechanism and characterize its puncturing stroke and force.
The Role of Tissue Slip Feedback in Robot-Assisted Surgery
Authors: Burkhard Natalie T. , Ryan Steger J. , Cutkosky Mark R.
Published: March 2019

Slip, or accidental loss, of grasped biological tissue can have negative consequences in all types of surgery (open, laparoscopic, robot-assisted). This work focuses on slip in robot-assisted surgery (RAS) with the goal of improving the quality of grasping and tool–tissue interactions. We report on a survey of 112 RAS surgeons, the results of which support the value of detecting and reducing slip in a variety of procedures. We conducted validation tests using a thermal slip sensor in a surgical grasper on tissue in vivo and ex vivo. The results of the survey and validation informed a user study to assess whether tissue slip feedback can improve performance and reduce effort in a phantom tissue manipulation task. With slip feedback, experienced subjects were significantly faster to complete the task, dropped tissue less (3% versus 38%), and experienced decreased mental demands and situational stress. These results provide motivation to further develop the sensor technology and incorporate it in robotic surgical equipment.
Comparing Predictive Accuracy and Computational Costs for Viscoelastic Modeling of Spinal Cord Tissues
Authors: Ramo Nicole L. , Troyer Kevin L. , Puttlitz Christian M.
Published: March 2019

The constitutive equation used to characterize and model spinal tissues can significantly influence the conclusions from experimental and computational studies. Therefore, researchers must make critical judgments regarding the balance of computational efficiency and predictive accuracy necessary for their purposes. The objective of this study is to quantitatively compare the fitting and prediction accuracy of linear viscoelastic (LV), quasi-linear viscoelastic (QLV), and (fully) nonlinear viscoelastic (NLV) modeling of spinal-cord-pia-arachnoid-construct (SCPC), isolated cord parenchyma, and isolated pia-arachnoid-complex (PAC) mechanics in order to better inform these judgements. Experimental data collected during dynamic cyclic testing of each tissue condition were used to fit each viscoelastic formulation. These fitted models were then used to predict independent experimental data from stress-relaxation testing. Relative fitting accuracy was found not to directly reflect relative predictive accuracy, emphasizing the need for material model validation through predictions of independent data. For the SCPC and isolated cord, the NLV formulation best predicted the mechanical response to arbitrary loading conditions, but required significantly greater computational run time. The mechanical response of the PAC under arbitrary loading conditions was best predicted by the QLV formulation.
Direct visualization of coexisting channels of interaction in CeSb
Authors: Jang Sooyoung , Kealhofer Robert , John Caolan , Doyle Spencer , Hong Ji-Sook , Shim Ji Hoon , Si Q. , Erten O. , Denlinger Jonathan D. , Analytis James. G.
Published: March 2019

ARPES reveals how correlated electrons reconcile competing interactions by separating them by orbital symmetry.
Increasing bulk photovoltaic current by strain tuning
Authors: Nadupalli Shankari , Kreisel Jens , Granzow Torsten
Published: March 2019

Bulk photovoltaic current in ferroelectric lithium niobate increases by 75% under a compressive mechanical stress of only 10 MPa.
Outstanding radiation resistance of tungsten-based high-entropy alloys
Authors: El-Atwani O. , Li N. , Li M. , Devaraj A. , Baldwin J. K. S. , Schneider M. M. , Sobieraj D. , Wróbel J. S. , Nguyen-Manh D. , Maloy S. A. , Martinez E.
Published: March 2019

Are high-entropy alloys the solution to radiation damage?
Making flexible spin caloritronic devices with interconnected nanowire networks
Authors: da Câmara Santa Clara Gomes Tristan , Abreu Araujo Flavio , Piraux Luc
Published: March 2019

We use macroscopic-scale magnetic nanowire network films to create efficient, flexible spin-thermoelectric devices.
Distinct signature of local tetrahedral ordering in the scattering function of covalent liquids and glasses
Authors: Shi Rui , Tanaka Hajime
Published: March 2019

A direct signature of tetrahedral ordering is revealed in the scattering function of silica and other tetrahedral materials.
Genetics of Group A Streptococci
Authors: Cho Kyu Hong , Port Gary C. , Caparon Michael
Published: March 2019

Streptococcus pyogenes
(group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been identified as potential virulence determinants for these diseases. A challenge is to link the function of potential virulence factors to the pathogenesis of specific diseases. An exciting advance has been the development of sophisticated genetic systems for the construction of loss-of-function, conditional, hypomorphic, and gain-of-function mutations in targeted
S. pyogenes
genes that can be used to test specific hypotheses regarding these genes in pathogenesis. This will facilitate a mechanistic understanding of how a specific gene function contributes to the pathogenesis of each streptococcal disease. Since the first
S. pyogenes
genome was completed in 2001, hundreds of complete and draft genome sequences have been deposited. We now know that the average
S. pyogenes
genome is approximately 1.85 Mb and encodes ∼1,800 genes and that the function of most of those genes in pathogenesis remains to be elucidated. However, advances in the development of a variety of genetic tools for manipulation of the
S. pyogenes
genome now provide a platform for the interrogation of gene/phenotype relationships for individual
S. pyogenes
diseases, which may lead to the development of more sophisticated and targeted therapeutic interventions. This article presents an overview of these genetic tools, including the methods of genetic modification and their applications.
Cervical carcinoma leading to orbital apex syndrome and blindness
Authors: Wadhwani Meenakshi , Phuljhele Swati , Kumar Ritesh , Shameer Abdul
Published: March 2019

Orbit is an unusual and rare site for metastases from cancer. The most frequent site of a primary malignancy to metastasise to the orbit is the breast, followed by the lung. The malignant mixed mullerian tumour is a rare uterine and cervical carcinoma and accounts for <5% of uterine cancers. It is the primary tumour of the uterus, and de novo involvement of the cervix itself is extremely rare. We report the first case of cervical carcinoma with mixed mullerian aetiology to be associated with orbital metastasis and eventually leading to blindness and death
Perilymphatic fistula and pneumolabyrinth without temporal bone fracture: a rare entity
Authors: Sousa Menezes Ana , Ribeiro Daniela , Miranda Daniel Alves , Martins Pereira Sara
Published: March 2019

Post-traumatic pneumolabyrinth is an uncommon clinical entity, particularly in the absence of temporal bone fracture. We report the case of a patient who presented to our emergency department with a headache, sudden left hearing loss and severe dizziness which began after a traumatic brain injury 3 days earlier. On examination, the patient presented signs of left vestibulopathy, left sensorineural hearing loss and positive fistula test, normal otoscopy and without focal neurological signs. The audiometry confirmed profound left sensorineural hearing loss. Cranial CT revealed a right occipital bone fracture and left frontal subdural haematoma, without signs of temporal bone fracture. Temporal bone high-resolution CT scan revealed left pneumolabyrinth affecting the vestibule and cochlea. Exploratory tympanotomy revealed perilymphatic fistula at the location of the round window. The sealing of defect was performed using lobule fat and fibrin glue. He presented complete resolution of the vestibular complaints, though the hearing thresholds remained stable.
What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from high-quality clinical practice guidelines: systematic review
Authors: Lin Ivan , Wiles Louise , Waller Rob , Goucke Roger , Nagree Yusuf , Gibberd Michael , Straker Leon , Maher Chris G , O’Sullivan Peter P B
Published: March 2019

Objectives

To identify common recommendations for high-quality care for the most common musculoskeletal (MSK) pain sites encountered by clinicians in emergency and primary care (spinal (lumbar, thoracic and cervical), hip/knee (including osteoarthritis [OA] and shoulder) from contemporary, high-quality clinical practice guidelines (CPGs).

Design

Systematic review, critical appraisal and narrative synthesis of MSK pain CPG recommendations.

Eligibility criteria

Included MSK pain CPGs were written in English, rated as high quality, published from 2011, focused on adults and described development processes. Excluded CPGs were for: traumatic MSK pain, single modalities (eg, surgery), traditional healing/medicine, specific disease processes (eg, inflammatory arthropathies) or those that required payment.

Data sources

Four scientific databases (MEDLINE, Embase, CINAHL and Physiotherapy Evidence Database) and four guideline repositories.

Results

6232 records were identified, 44 CPGs were appraised and 11 were rated as high quality (low back pain: 4, OA: 4, neck: 2 and shoulder: 1). We identified 11 recommendations for MSK pain care: ensure care is patient centred, screen for red flag conditions, assess psychosocial factors, use imaging selectively, undertake a physical examination, monitor patient progress, provide education/information, address physical activity/exercise, use manual therapy only as an adjunct to other treatments, offer high-quality non-surgical care prior to surgery and try to keep patients at work.

Conclusion

These 11 recommendations guide healthcare consumers, clinicians, researchers and policy makers to manage MSK pain. This should improve the quality of care of MSK pain.
Co-creation of patient engagement quality guidance for medicines development: an international multistakeholder initiative
Authors: Deane Katherine , Delbecque Laure , Gorbenko Oleksandr , Hamoir Anne Marie , Hoos Anton , Nafria Begonya , Pakarinen Chi , Sargeant Ify , Richards Dawn P , Skovlund Soren Eik , Brooke Nicholas
Published: March 2019

Introduction

Meaningful patient engagement (PE) can enhance medicines’ development. However, the current PE landscape is fragmentary and lacking comprehensive guidance.

Methods

We systematically searched for PE initiatives (SYNaPsE database/publications). Multistakeholder groups integrated these with their own PE expertise to co-create draft PE Quality Guidance which was evaluated by public consultation. Projects exemplifying good PE practice were identified and assessed against PE Quality Criteria to create a Book of Good Practices (BOGP).

Results

Seventy-six participants from 51 organisations participated in nine multistakeholder meetings (2016–2018). A shortlist of 20relevant PE initiatives (from 170 screened) were identified. The co-created INVOLVE guidelines provided the main framework for PE Quality Guidance and was enriched with the analysis of the PE initiatives and the PE expertise of stakeholders. Seven key PE Quality Criteria were identified. Public consultation yielded 67 responses from diverse backgrounds. The PE Quality Guidance was agreed to be useful for achieving quality PE in practice, understandable, easy to use, and comprehensive. Overall, eight initiatives from the shortlist and from meeting participants were selected for inclusion in the BOGP based on demonstration of PE Quality Criteria and willingness of initiative owners to collaborate.

Discussion

The PE Quality Guidance and BOGP are practical resources which will be continually updated in response to user feedback. They are not prescriptive, but rather based on core principles, which can be applied according to the unique needs of each interaction and initiative. Implementation of the guidance will facilitate improved and systematic PE across the medicines’ development lifecycle.
Elucidating bidirectional relationship between metabolic syndrome and elevated faecal haemoglobin concentration: a Taiwanese community-based cohort study
Authors: Ku Mei-Sheng , Fann Jean Ching-Yuan , Chiu Sherry Yueh-Hsia , Chen Hsiu-Hsi , Hsu Chen-Yang
Published: March 2019

Objectives

To elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS).

Design

A longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS.

Setting

Population-based organised integrated service screening in Keelung city, Taiwan.

Participants

We enrolled a total of 62,293 community residents aged 40–79 years.

Main outcomes and measures

Bidirectional outcomes of FIT-positive and MetS were measured.

Results

The presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein).

Conclusions

Our finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.
Consumption trends and prescription patterns of opioids from 2011 to 2016: a survey in a Chinese city
Authors: Liu Xiao , Luo Can , Dai Huizhen , Fang Wentong
Published: March 2019

Objective

Opioid consumption in China has been very less and has varied widely since 1995. The representatively high level of consumption in Mainland China has never been reported. Our aim was to describe the consumption trends and prescription patterns of opioids in Nanjing, a highly developed city of Mainland China, and compare the results with selected worldwide regions.

Methods

Application data of opioids in 2011–2016 were extracted from the Jiangsu Medicine Information Institute. Six opioids were included. Consumption was expressed in terms of defined daily doses (DDDs), morphine equivalents (MEs) and expenditure. The correlation between consumption of opioids and gross domestic product (GDP), Human Development Index (HDI) and cancer incidence was analysed by Pearson’s correlation test.

Results

DDDs, expenditure and MEs of opioids were, respectively, 256.04, $599.24 and 13.07 g in 2011, and increased to 361.27, $1041.79 and 18.09 g in 2016. DDDs in Nanjing were 2.80-fold that in Mainland China, 1.42-fold that in East and South-East Asia, but only equivalent to 8.89% of the worldwide average level. From 2011 to 2016, the consumption had a linear correlation with GDP, HDI and cancer incidence (p<0.05). However, DDDs varied greatly in countries with similar GDP or HDI. Within 45 Asian countries, the GDP only contributed to 10.47% of change in DDDs, while the HDI contributed to 20.32%. Consumption of non-intravenous opioids or strong opioids always comprised majority of the total consumption. The opioids prescribed predominantly were fentanyl, oxycodone and morphine. Fentanyl and oxycodone account for most of the increase in consumption.

Conclusion

Opioid consumption has increased >40% from 2011 to 2016, with consumption of fentanyl and oxycodone accounting for most of that increase. The consumption in Nanjing was higher than the average Chinese level, but lower than the global average. An increase in pain control services might be needed, but this need should be highly regulated.