bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of the forward Na+/Ca2+ exchanger suppresses the growth of glioblastoma cells through Ca2+‐mediated cell death
Authors: Hu Hui‐Jie , Wang Shan‐Shan , Wang Yan‐Xia , Liu Yan , Feng Xue‐Mei , Shen Ying , Zhu Liang , Chen Hong‐Zhuan , Song Mingke
Published: April 2019

Background and Purpose

The Na+/Ca2+ exchanger (NCX) working in either forward or reverse mode participates in maintaining intracellular Ca2+ ([Ca2+]i) homeostasis, which is essential for determining cell fate. Previously, numerous blockers targeting reverse or forward NCX have been developed and studied in ischaemic tissue injury but barely examined in glioblastoma for the purpose of anti‐tumour therapy. We assessed the effect of NCX blockers on glioblastoma growth and whether NCX can become a therapeutic target.

Experimental Approach

Patch‐clamp recording, Ca2+ imaging, flow cytometry, and Western blot were used to study the effects of specific and non‐specific NCX blockers on cultured glioblastoma cells. In vivo bioluminescent imaging was used to measure effects on grafted glioblastoma.

Key Results

Selectively blocking the reverse NCX with SEA0400, SN‐6, and YM‐244769 did not affect tumour cell viability. Blocking the forward NCX with bepridil, CB‐DMB, or KB‐R7943 elevated [Ca2+]i and killed glioblastoma cells. Bepridil and CB‐DMB caused Ca2+‐dependent cell cycle arrest together with apoptosis, which were all attenuated by a Ca2+ chelator BAPTA‐AM. Systemic administration of bepridil inhibited growth of brain‐grafted glioblastoma. Bepridil did not appear to have a cytotoxic effect on human astrocytes, which have higher functional expression of NCX than glioblastoma cells.

Conclusions and Implications

Low expression of the NCX makes glioblastoma cells sensitive to disturbance of [Ca2+]i. Interventions designed to block the forward NCX can cause Ca2+‐mediated injury to glioblastoma thus having therapeutic potential. Bepridil could be a lead compound for developing new anti‐tumour drugs.
Sexual differences rather than flight performance underlie movement and exploration in a tropical butterfly
Authors: Reim Elisabeth , Kahl Stefan , Metschke Katja , Fischer Klaus
Published: April 2019

1. Individual movement behaviour governs several routine processes, and may scale up to important ecological processes, including dispersal. However, movement is affected by a wealth of factors, including abiotic conditions, flight performance, and behavioural traits. Although it has been historically assumed that insect flight is in the first place ruled by physiology and morphology, researchers have only recently begun to understand the potentially important role of behavioural traits.

2. This study aims to disentangle the relative importance of thermal conditions during development, and especially flight performance (capacity), versus behaviour (intrinsic motivation) in relation to movement attributes (i.e. time until take‐off, number of positions visited) under controlled laboratory conditions in the tropical butterflyBicyclus anynana.

3. As predicted, links were found between flight performance (forced flight) and morphological traits (body size). However, this link was less pronounced for movement and exploratory behaviour, suggesting a more pronounced role of intrinsic motivation on the actual decision to move, or not. Thus, flight performance and movement may not be intimately associated.

4. Flight behaviour was mainly determined by sexual differences, with males showing better flight performance, higher mobility, and enhanced exploration than females.

5. Lower developmental temperatures increased thorax–abdomen ratio, thorax mass, and exploratory behaviour, and decreased wing loading. This may potentially aid flight capacity under thermally challenging conditions.

6. This study adds to the growing evidence that behavioural traits should not be neglected when investigating movement and dispersal, as they may well play a crucially important role.
Specialisation in prey capture drives coexistence among sympatric spider‐hunting wasps
Authors: Moura Rafael R. , Pitilin Renan B. , Buschini Maria L.T.
Published: April 2019

1. Sister taxa that coexist in the same space and time often face competition due to the use of similar resources. However, some closely related species can adopt fine‐grained specialisation in resource use to coexist. This study investigated niche overlap between three sympatric spider‐hunting wasp species of the genus Trypoxylon (Hymenoptera: Crabronidae) known to nest in three of the habitats found in the study area.

2. First, the co‐occurrence of these wasp species in the three habitats was estimated, as a proxy for potential competition. Then, the following hypotheses were tested: (i) niche partitioning is seen more often between species that co‐occur in a habitat, whereas there is niche overlap between species nesting in distinct habitats (prey specialisation hypothesis); and (ii) wasp species capture prey according to their size (physical constraint hypothesis).

3. Two pairs of wasp species were found consistently nesting in the same habitat. Niche partitioning based on prey taxa occurred regardless of the habitat preference. It was also found that differences in the size of wasps reflected distinctions in the size of their prey.

4. These findings were consistent over the years, showing that the significance of specialisation in foraging activities and physical constraints during prey capture can play key roles in the coexistence of sympatric species. The distinctions in the foraging strategies of these wasps are discussed, as well as potential mechanisms driving the evolution in prey specialisation, with insights for future studies.
Bone tissue response to an MTA‐based endodontic sealer, and the effect of the addition of calcium aluminate and silver particles
Authors: Almeida L. H. , Gomes A. P. N. , Gastmann A. H. , Pola N. M. , Moraes R. R. , Morgental R. D. , Cava S. S. , Felix A. O. C. , Pappen F. G.
Published: April 2019

Aim

To evaluate bone tissue reactions in rats to an MTA‐based endodontic sealer with and without the addition of various concentrations of C3A or C3A + Ag.

Methodology

Bone tissue reactions were evaluated in 45 Wistar rats after 7, 30 and 90 days (n = 5 per period). Three surgical cavities were prepared on the right femur and filled with 0.2 mL MTA Fillapex, MTA Fillapex + C3A and C3A + Ag at various concentrations: AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany), EndoSequence BC (Brasseler USA, Savannah, GA, USA) or no sealer (negative control). By the end of each experimental period, animals were randomly euthanized. The samples were histologically processed and analysed using a light microscope. The presence of inflammatory cells, fibres and hard tissue barrier formation was evaluated. Data were analysed statistically using nonparametric tests to compare the differences between groups. Multiple groups were compared using the Kruskal–Wallis and Mann–Whitney U‐tests with a Bonferroni correction at P = 0.05.

Results

The inflammatory response significantly decreased from 30 to 90 days (P < 0.05). Fibre condensation was similar amongst the groups at 07 and 30 days after intervention (P > 0.05). At 90 days, however, fibres were absent in most specimens of EndoSequence BC Sealer, AH Plus, MTA Fillapex and the control group, whilst they were still observed in samples of the modified sealers (P < 0.05). At 90 days, all specimens of AH Plus, EndoSequence BC Sealer and control group had complete formation of hard tissue barrier. In the MTA Fillapex group, as well as in the modified sealers groups, partial deposition of mineralized tissue was noticed.

Conclusion

The hypothesis tested that the incorporation of C3A and C3A + Ag particles to MTA Fillapex would improve bone tissue repair was partially accepted, since modified MTA Fillapex did not have the same repair potential as the commercial bioceramic material.
Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals
Authors: Tian Lei , Su Cong‐Ping , Wang Qing , Wu Fu‐Jian , Bai Rui , Zhang Hui‐Min , Liu Jin‐Ying , Lu Wen‐Jing , Wang Wei , Lan Feng , Guo Shu‐Zhen
Published: April 2019

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti‐inflammatory, anti‐oxidant and anti‐apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)‐induced heart failure mouse model, through mitigating the TNF‐α–induced toxicity. We further used TNF‐α‐induced cardiac injury in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) to elucidate the underlying mechanisms. CGA pre‐treatment could reverse TNF‐α–induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF‐κB/p65 and major mitogen‐activated protein kinases (MAPKs) signalling pathways involved in TNF‐α–induced apoptosis of hiPSC‐CMs. Importantly, CGA can directly inhibit NF‐κB signal by suppressing the phosphorylation of NF‐κB/p65. As for the MAPKs, CGA suppressed the activity of only c‐Jun N‐terminal kinase (JNK), but enhanced extracellular signal‐regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF‐κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.
Methyl 3,4-dihydroxybenzoate protects against d-galN/LPS-induced acute liver injury by inhibiting inflammation and apoptosis in mice
Authors: Wang Xiangpeng , Wu Lulu , Zhang Quanshu , Li Lili , Xie Yanni , Wan Xing , Wu Hao , Xiang Yang
Published: April 2019

Objectives

Aimed to investigate the effect and mechanism of methyl 3,4-dihydroxybenzoate (MDHB) on d-galactosamine/lipopolysaccharide (d-galN/LPS)-induced acute liver failure (ALF).

Methods

Confirmed the hepatoprotective effect and hepatotoxicity of MDHB by histopathological examination (HE) and examination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); the expression of serum tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) was detected by ELISA; transcription levels of TNF-α, IL-1β, IL-6 and Toll-like receptor 4 (TLR4) were detected by qRT-PCR; and phosphorylation levels of p38 and p65 were analysed by Western blot.

Results

Histopathological examination and examination of ALT and AST confirmed that MDHB is a low toxicity drug that can resist d-galN/LPS-induced ALF; MDHB can effectively reduce high transcription and expression of TNF-α, IL-1β, IL-6 and TLR4 in d-galN/LPS-induced ALF; and Western blot showed that MDHB could down-regulate the expression of bax, up-regulate the expression of bcl-xl and bcl-2, and inhibit the phosphorylation of p38 and p65.

Conclusions

Methyl 3,4-dihydroxybenzoate can effectively resist d-galN/LPS-induced acute liver failure, which is related to the inhibition of inflammation and apoptosis.
Co‐registration of panoramic mobile mapping images and oblique aerial images
Authors: Fanta‐Jende Phillipp , Nex Francesco , Vosselman George , Gerke Markus
Published: April 2019

Mobile mapping relies on satellite‐based positioning, which suffers from line‐of‐sight and multipath issues. As an alternative, this paper presents a fully automatic approach for the co‐registration of mobile mapping and oblique aerial images to introduce highly accurate and reliable ground control for mobile mapping data adjustment. An oblique view of a scene introduces similarities as well as challenges regarding co‐registration with mobile mapping images, which is supported by mutual planes in both datasets. Façade planes from a sparse point cloud are used as projection surfaces for the mobile mapping and aerial datasets, overcoming large perspective differences between them to simplify the registration. The performance of the procedure indicates an inlier rate of around 80%.
Varieties of Policy Feedback Research: Looking Backward, Moving Forward
Authors: Béland Daniel , Schlager Edella
Published: April 2019

Policy feedback refers to the variety of ways in which existing policies can shape key aspects of politics and policymaking. Originating in historical institutionalism, the study of policy feedback has expanded to address resource and interpretative effects on target populations and mass publics, the roles of policy elites, and how feedback effects are conditioned by policy designs and larger institutional contexts. Recently, more attention has also been paid to feedback effects that are not self‐reinforcing in nature. This introduction provides a nonexhaustive review of the existing historical institutionalist literature on policy feedback as well as introducing the contributions to the special issue. The diversity of policy feedback scholarship is reflected in manuscripts building from the social constructions framework and the thermostatic model. Advances in research are captured in contributions empirically testing different forms of feedback, varied strategies of policy elites to shape feedback, and how context may suppress feedback effects. The special issue emphasizes critical, understudied dimensions shaping feedback processes, such as race, and the role of organizations. A major lacuna in policy feedback scholarship, the overwhelming emphasis on the United States, must be addressed through more comparative and international research including closer dialogs between U.S.‐based and non‐U.S. scholars.
Women's relationships with women at work: Barriers to solidarity
Authors: Webber Gretchen R. , Giuffre Patti
Published: April 2019

Voluminous scholarship documents the wage gap, occupational segregation, sexual harassment, and other forms of gender inequality at work. Few sociological studies explore women's work relationships with other women. Our article summarizes existing research from several disciplines on women's working relationships with other women. Specifically, three themes about the conditions of work emerge that discourage women's support for other women: (a) negative stereotypes about women, (b) lack of recognition of gender inequality, and (c) the devaluation of women's relationships, groups, and networks. We assert that these conditions reinforce essentialized notions of women, ignore larger structural inequalities at work, and cast women as the primary culprit in perpetuating gender inequality at work. We conclude with promising areas for future research on women's working relationships with other women.
Life satisfaction among inbound university students in northern Sweden
Authors: Nilsson Per Anders , Stålnacke Britt-Marie
Published: April 2019

Will life satisfaction among international students change after having an experience of studying abroad? Some previous studies indicate inequalities and issues of social mobility embedded in international student mobility. International student mobility implies physical movement and new experiences gained while studying abroad. The ubiquity of international students and their generally successful adaptation makes it necessary to understand how they manage to turn a seemingly difﬁcult situation into satisfying adaptation. One area of such concern that this study sought to explore was the students’ level of satisfaction with life. This study investigated the self-reported life satisfaction of inbound university students upon arrival to a university in northern Sweden and at follow-up six months later. After the study period abroad, the students’ levels of perceived satisfaction with their somatic health and activities of daily living had significantly increased. Higher levels, while non-significant, were found for the domains life as a whole, study situation and economy. These findings may indicate that studying abroad could have an impact on students’ reported life satisfaction, which highlights the value of a period of studying abroad. However, when exploring life satisfaction outcomes among internationally mobile students, it seems pertinent to study student mobility within a context. This study mostly targets international student mobility in a Western/European context.
Lakes, presidents and shopping on mental maps: children’s perceptions of the Finnish–Russian border and the borderland
Authors: Kaisto Virpi , Brednikova Olga
Published: April 2019

The Finnish–Russian borderland has transformed in the last three decades from two isolated national territories into a transition zone, where the ‘other’ culture and society is ever more present. This paper analyses what kinds of perceptions Finnish and Russian children have of the border and the borderland today. It also examines children’s territorial identifications in the borderland. The research is based on 263 mental maps collected from 9–15-year-old children in the cities of Lappeenranta (Finland) and Vyborg (Russia) and the village of Pervomayskoe (Russia) between 2013 and 2017. The analysis of the maps illustrates that the children participating in the study perceive the Finnish–Russian border mainly as a place for border crossings, although they continue to use the border as a tool for constructing socio-spatial distinctions. In this way, the children actively participate in processes of bordering and play an important part in the social life of the borderland. The participants’ perceptions of the borderland are connected to the national and local contexts that they live in but vary widely between individuals. The paper argues that the local border-related phenomena and children’s border-crossing experiences are increasingly relevant for their national and local identification processes. Besides providing novel information regarding Finnish and Russian children’s perceptions and identifications in the Finnish–Russian borderland, the paper adjusts the mental mapping method to a borderland context and enhances our understanding of the complexity of the bordering processes taking place in borderlands.
Lectio praecursoria: Theory of control tuning – the processing of control in migration-related place coping
Authors: Niemi Saija
Published: April 2019

In this lectio praecursoria, which I presented as part of my doctoral defence at the University of Helsinki on 26 October 2018, I introduce a new migration-related control theory that I developed in my doctoral research. The theory of control tuning is a middle-range theory that closes the gap between empirical data and formal theory. The theory is mainly based on primary data from South Sudanese migration, which I brought from the descriptive level to the conceptual level by using classic grounded theory methodology. The theory of control tuning explains how various migration actors process control in their everyday life in order to manage and govern feelings, information, actions and people as well as ownership of situations and objects. Control tuning refers to the action of modifying control, and it occurs through particular control-tuning paths. These control-tuning paths consist of control-tuning causes, strategies, outcomes, intervening factors and conditions. Control-tuning paths appear in relation to the behavioural arena of migration. This behavioural arena includes the elements, circumstances, relationships and objects of the physical, social, political, cultural and economic world with which migration actors come into contact and interact. The main activities in the behavioural arena of migration are place coping, knowledge dealing, encountering authority and link keeping. The theory of control tuning demonstrates that control tuning occurs regardless of whether migration is international or internal or forced or voluntary and irrespective of the status of a migrant, or whether the actor is a local resident or an authority, or whether migration actors move or stay put. Moreover, the theory of control tuning demonstrates that control has significance for individuals and groups of migration actors.
R.I.P. Resilience
Authors: Andresen Silje Aurora
Published: April 2019

Resilience was set to rest on 30 June 2016 in Trondheim, Norway. After a two-year quest for meaning, the concept now lies with its neoliberal supporters. Resilience and I first crossed paths at the beginning of my PhD journey in Geography. I was driven by curiosity and an eagerness to put resilience to use: after all, who doesn’t want to be resilient? As the months passed by, I discovered the many different meanings the concept was associated with. Indeed, resilience refused to be put in a box. Yet, the concept contained some questions that I set out to try to answer in the “real” world. However, curiosity soon developed into frustration – resilience revealed a rootlessness that was disturbing. Was it a means to measure? A means to conceptualize why some people make it and some do not? Or, was it in fact, just a means to get funding? Certainly, it was not a means to explain. Therefore, resilience will for me forever be remembered as an approach to enter and structure an interview guide, but now we must bid one another farewell. Your legacy will continue to live on in the neoliberal agenda.
Analytical and Low-Order Numerical Modeling of Ball-to-Ball Contact Friction in Linear Ball Bearings and Ball Screws
Authors: Lin Bo , Duan Molong , Okwudire Chinedum E.
Published: April 2019

Analytical and low-order numerical models are very useful for studying friction behavior of rolling element machine components like ball bearings and ball screws. This is because they provide generalizable insights into friction behavior at much lower computational costs compared with high-order numerical models like finite element analysis (FEA). While analytical and low-order numerical models in the literature are mainly focused on ball-to-groove contact friction, experimental studies have shown that ball-to-ball contact friction is also very important. This is especially true for linear ball bearings/guideways and ball screws which, unlike rotary ball bearings, do not typically make use of caged balls to prevent ball-to-ball contact. Therefore, in this paper, low-order numerical models for ball-to-ball contact friction in linear ball bearings and ball screws are developed. Furthermore, an analytical model for ball-to-ball contact friction in four-point contact linear ball bearing is derived by making simplifications to its low-order numerical model. Compared with ball-to-ball friction predictions from FEA models developed in ansys, the proposed numerical models are shown in case studies to be accurate within 7%, while computing at least three orders of magnitude faster. Moreover, case studies are used to demonstrate how the developed models can be used in practice, e.g., for the mitigation of ball-to-ball contact friction in linear ball bearings and the prediction of friction variation during the operation of a ball screw.
A Numerical Simulation for the Determination of the Shunt Ratio at a T-Junction With Different Branch Angles, Viscosities, and Flow Rates
Authors: Zhang Nan , Li Haitao , Zhang Yunbao , Deng Qing , Tan Yongsheng
Published: April 2019

T-junctions have been applied in water-control structures. A comprehensive understanding of shunt characteristics can contribute to the optimal design of T-junctions. In this work, we seek to understand the shunt ratio of fluids with different viscosities in a T-junction and to achieve a greater shunt ratio. The computational fluid dynamics (CFD) approach is applied to study the influence of the properties, such as the fluid viscosity, the branch angle, the channel shape, and the flow rate, on the shunt ratio in a T-junction. The viscosity of oil can be divided into three intervals, and the optimal angles of the T-junction are different in each interval. For the fluid viscosity in the 1–20 cP range, the optimal branch angle is in the 45–60 deg range. For the fluid viscosity in the 20–65 cP range, the branch angle should be designed to be 45 deg. For the viscosity greater than 65 cP, the branch angle should be designed to be 75 deg. The appearance of the eddy and secondary flow will reduce the flow. The secondary flow and eddy intensity on the branch increase with increasing angle. The secondary flow intensity of the main channel decreases gradually with the increase in the angle. This study provides an important guidance for the design of automatic water control valve tools.
Investigation of Active Power Cycling Combined With Passive Thermal Cycles on Discrete Power Electronic Devices
Authors: Otto Alexander , Rzepka Sven , Wunderle Bernhard
Published: April 2019

Active power cycling (APC) is a standardized and well-established method for reliability assessment and product qualification in power electronics (PEs) technologies. Repetitive pulses of load current are applied to cause cyclic thermal swings in the p–n junction and in the whole semiconductor device. They induce thermo-mechanical stresses, which ultimately leads to the typical interconnect failure in the “devices under test.” However, these tests are insensitive with respect to new automotive system architectures, in which PEs devices are exposed to additional loads besides the intrinsic thermal swings. The trends in PEs toward miniaturization, higher power density, heterogeneous system integration, and the deployment of PEs in harsher environments combined with longer lifetime and higher uptime requirements strongly increase the reliability demands in general and the need for more improved reliability assessment methodologies in particular. The new testing methods shall be more comprehensive and more efficient, i.e., they shall simultaneously cover the real service conditions better and reduce testing time. One promising approach is the combination of loading factors—such as the superposition of active power cycling by passive thermal cycles (TC). Both loading factors are well known to cause most relevant failure mechanisms in PEs. In reality, the PE devices are exposed to both factors simultaneously. Hence, this load case should also be replicated in the test. The paper will report a systematic investigation of such superimposed test schemes, which cover the case of self-heating and passive heating (from neighboring elements) of the PEs devices under real service conditions. Typical discrete PEs components in TO-200 packages are selected as test vehicles as they are likewise relevant for the domains of consumer or automotive electronics. The paper details the test concept and discusses the quantitative and qualitative test results.
Reverberation time and audibility in phased geometrical acoustics using plane or spherical wave reflection coefficients
Authors: Boucher Matthew A. , Rychtarikova Monika , Zelem Lukáš , Pluymers Bert , Desmet Wim
Published: April 2019

Room acoustics parameters are typically predicted using some form of geometrical acoustics for large rooms. For smaller rooms, phased geometrical acoustics improves results for lower frequencies. The use of a spherical wave reflection coefficient improves the results further, yet the exact impact on room acoustics parameters is not fully known. This work predicts the reverberation time in medium-sized rooms (27 m3 < V < 300 m3) using phased geometrical acoustics. The difference between the use of plane and spherical wave reflection modeling is analyzed for a variety of boundary conditions, including non-uniform distribution of absorption. Since calculated differences are greater than the conventional just-noticeable-difference of 5% for reverberation time, laboratory listening tests are performed to confirm audibility of the modeled differences. Two narrow band noise stimuli (octave bands with central frequency 125 and 250 Hz) with a duration of 1 s were used for comparisons of 18 acoustic scenarios by means of a three-alternative forced choice method. More than half of the listeners could hear the differences in all 36 cases. Statistically significant results (chi-squared test was used) were found in two-thirds of the cases, corresponding to those with longer reverberation times.
Audibility of dispersion error in room acoustic finite-difference time-domain simulation in the presence of a single early reflection
Authors: Saarelma Jukka , Savioja Lauri
Published: April 2019

Finite-difference time-domain method has gained increasing interest for room acoustic prediction use. A well-known limitation of the method is a frequency- and direction-dependent dispersion error. In this study, the audibility of dispersion error in the presence of a single surface reflection is measured. The threshold is measured for three different distance conditions with a fixed reflection arrival azimuth angle of 54.7°. The error is placed either in the direct path, or in the reflection path. Additionally a qualitative follow-up experiment to evaluate how the measured thresholds reflect the audibility of error in short room responses is carried out. The results indicate that the threshold varies depending whether the error is in the direct path or in the reflection path. For transient signals the threshold is higher when the error is located in the direct path, whereas for speech signal, the threshold is higher when it is located in the reflection path. Evidence is found that the error is detectable in rendered room responses at the measured threshold levels.
Machine-learning-based estimation and rendering of scattering in virtual reality
Authors: Pulkki Ville , Svensson U. Peter
Published: April 2019

In this work, a technique to render the acoustic effect of scattering from finite objects in virtual reality is proposed, which aims to provide a perceptually plausible response for the listener, rather than a physically accurate response. The effect is implemented using parametric filter structures and the parameters for the filters are estimated using artificial neural networks. The networks may be trained with modeled or measured data. The input data consist of a set of geometric features describing a large quantity of source-object-receiver configurations, and the target data consist of the filter parameters computed using measured or modeled data. A proof-of-concept implementation is presented, where the geometric descriptions and computationally modeled responses of three-dimensional plate objects are used for training. In a dynamic test scenario, with a single source and plate, the approach is shown to provide a similar spectrogram when compared with a reference case, although some spectral differences remain present. Nevertheless, it is shown with a perceptual test that the technique produces only a slightly lower degree of plausibility than the state-of-the-art acoustic scattering model that accounts for diffraction, and also that the proposed technique yields a prominently higher degree of plausibility than a model that omits diffraction.
Boundary absorption approximation in the spatial high-frequency extrapolation method for parametric room impulse response synthesis
Authors: Southern Alex , Murphy Damian T. , Savioja Lauri
Published: April 2019

The spatial high-frequency extrapolation method extrapolates low-frequency band-limited spatial room impulse responses (SRIRs) to higher frequencies based on a frame-by-frame time/frequency analysis that determines directional reflected components within the SRIR. Such extrapolation can be used to extend finite-difference time domain (FDTD) wave propagation simulations, limited to only relatively low frequencies, to the full audio band. For this bandwidth extrapolation, a boundary absorption weighting function is proposed based on a parametric approximation of the energy decay relief of the SRIR used as the input to the algorithm. Results using examples of both measured and FDTD simulated impulse responses demonstrate that this approach can be applied successfully to a range of acoustic spaces. Objective measures show a close approximation to reverberation time and acceptable early decay time values. Results are verified through accompanying auralizations that demonstrate the plausibility of this approach when compared to the original reference case.
On the effect of streamwise disturbance on the airfoil-turbulence interaction noise
Authors: Zhong Siyang , Zhang Xin
Published: April 2019

Usually the prediction of airfoil-gust interaction noise is mainly based on the flat plate solution, and only the transverse velocity disturbance that is perpendicular to the flat plate surface is considered. However, the solution might underestimate the sound generation in non-uniform mean flows for finite thickness airfoils, in which the velocity disturbance in the streamwise direction could probably produce sound as well. The effect is studied in this work by using both numerical simulations and theoretical analysis. To highlight the effect of streamwise disturbance, the anisotropic turbulences with constant transverse velocity components while varying streamwise components are employed, which can be realised by adjusting the integral length scales in the Gaussian energy spectra. The simulation results explicitly show that more sound is produced by the streamwise components for airfoils at higher Mach numbers when the flow non-uniformities are more significant. An analytical model based on acoustic analogy to account for the sound generation by the coupling between the gust and non-uniform mean flows is proposed, which explains the observations in the numerical simulation well. Also, a correction to Amiet's flat plate solution using the proposed model yields better agreement with the numerical results, especially for anisotropic turbulences with larger integral length scale in the streamwise direction.
Efficiency in glimpsing vowel sequences in fluctuating makers: Effects of temporal fine structure and temporal regularity
Authors: Shen Yi , Pearson Dylan V.
Published: April 2019

Listeners' efficiency in glimpsing the target speech in amplitude-modulated maskers may depend on whether the target is perceptually segregated from the masker and on the temporal predictability of the target. Using synthesized vowel sequences as the target, recognition of vowel sequences in simultaneous amplitude-modulated noise maskers was measured as the signal-to-noise ratio (SNR) and the masker modulation rate were systematically varied. In Experiment I (Exp. I), the temporal fine structure of the target was degraded by synthesizing the vowels using iterated rippled noise as the glottal source. In Experiment II (Exp. II), the vowel sequences were constructed so that they were not isochronous, but instead contained randomized intervals between adjacent vowels. Results were compared to the predictions from a dip-listening model based on short-term SNR. The results show no significant facilitative effect of temporal fine structure cues on vowel recognition (Exp. I). The model predictions significantly overestimated vowel-recognition performance in amplitude-modulated maskers when the temporal regularity of the target was degraded (Exp. II), suggesting the influence of temporal regularity on glimpsing efficiency. Furthermore, the overestimations by the model were greater at lower SNRs and selective to moderate masker modulation rates (between 2 and 6 Hz).
CD13 tethers the IQGAP1-ARF6-EFA6 complex to the plasma membrane to promote ARF6 activation, β1 integrin recycling, and cell migration
Authors: Ghosh Mallika , Lo Robin , Ivic Ivan , Aguilera Brian , Qendro Veneta , Devarakonda Charan , Shapiro Linda H.
Published: April 2019

The cell surface peptidase CD13 coordinates β1 integrin recycling to promote cell migration.
Endoscopic treatment of a periorbital fat herniation caused by spontaneous solution of continuity of the papyracea lamina
Authors: Galletti Bruno , Gazia Francesco , Galletti Cosimo , Galletti Francesco
Published: April 2019

We present a case of a 16-year-old girl with interruption of papyracea lamina and herniation of the periorbital fat covered by a bone shell. The patient presents with a history of diplopia and visual disturbances ever since she can remember. Thanks to radiological imaging and biopsy, we have done differential diagnosis with periorbital lipoma, intraosseous lipoma and intramuscular lipoma of medial rectus. Diagnostic for images is necessary for a correct operative planning. Endoscopic sinus surgery with computer-assisted navigation is the safest and most effective method to remove the lesion that was closely related to the medial rectum muscle and to the anterior ethmoidal artery. The patient after surgery and in 1 year of follow-up reports the disappearance of symptoms.
Acute myocardial infarction and haemodynamic stroke in a young patient with Bardet-Biedl syndrome
Authors: Alexander Vijay , George Tina , Devarajan Gifty , Zachariah Anand
Published: April 2019

A 28-year-old man diagnosed with diabetes mellitus and systemic hypertension presented with a medical history of sudden onset retrosternal discomfort followed by loss of consciousness and generalised tonic clonic seizures. Examination revealed obesity, polysyndactyly and retinal pigment dystrophy. He was diagnosed to have acute myocardial infarction and left posterior watershed infarct. He was also diagnosed to have Bardet-Biedl syndrome based on clinical features. He was managed symptomatically and is currently doing well on regular follow-up in the outpatient clinic.
Posterior segment drug delivery for the treatment of exudative age-related macular degeneration and diabetic macular oedema
Authors: Wong Chee Wai , Wong Tina T
Published: April 2019

Inhibitors of vascular endothelial growth factors are used to treat a myriad of retinal conditions, including exudative age-related macular degeneration (AMD), diabetic macular oedema (DME) and diabetic retinopathy. Although effective, long-term efficacy is limited by the need for frequent and invasive intravitreal injections. The quest for sustained action therapeutics that can be delivered to target tissue in the least invasive manner is an arduous endeavour that has ended in premature failure for several technologies in Phase II or III trials. Nevertheless, there have been promising preclinical studies, and more are on the horizon: port delivery systems for the treatment of exudative AMD have entered Phase III trials and a wide array of preclinical studies have demonstrated the potential for nanoparticles, such as liposomes, dendrimers and cell penetrating peptides to deliver therapeutics into the posterior segment via minimally invasive routes. In this review, we discuss the challenges posed by ocular barriers for drug penetration and present the recent advancements of the most pertinent drug delivery platforms with a focus on the treatment of exudative AMD and DME.
Shared decision making for thromboembolic prophylaxis in non-valvular atrial fibrillation: promise and problems with the American College of Cardiology’s AnticoagEvaluator (based on SPARCtool)
Authors: Mayer Martin
Published: April 2019

Background and methods

People with atrial fibrillation face an increased risk of thromboembolic events, and deciding on an antithromboembolic strategy in non-valvular atrial fibrillation is a prime opportunity for shared decision making. Therefore, tools facilitating this process are highly desirable. The American College of Cardiology strives for such with its ‘AnticoagEvaluator’, which is based on Peter Loewen’s ‘SPARCtool’. However, it appears these tools were released without standard peer review. Therefore, an analysis of these tools was undertaken to evaluate their soundness, namely proper use of baseline risk and effect estimates from the available evidence.

Results

Despite Loewen’s laudable idea and the American College of Cardiology developing AnticoagEvaluator based on Loewen’s work, both tools have a flaw: they use relative effect estimates based on composite outcomes (thromboembolic and haemorrhagic) that do not match the baseline risk to which they are applied (thromboembolic). This can lead to importantly inaccurate impressions of therapeutic efficacy. This analysis explores this issue and offers potential solutions.

Conclusions

The American College of Cardiology releasing and promoting a tool that gives misleading impressions of therapeutic efficacy is of considerable importance, though SPARCtool should also be corrected as a matter of importance. Means to correct the tools are identified herein, and if corrected, these tools stand to better fulfil their intended purpose as important and useful additions for clinical and shared decision making. This article’s analysis of the tools has a directly practical purpose, but it also serves as an instructive example of key elements of evidence-based medicine and shared decision making.
Assessing the non-inferiority of prosthesis constructs used in total and unicondylar knee replacements using data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man: a benchmarking study
Authors: Deere Kevin C , Whitehouse Michael R , Porter Martyn , Blom Ashley W , Sayers Adrian
Published: April 2019

Objectives

To investigate the relative performance of knee replacement constructs compared with the best performing construct and illustrate the substantial variability in performance.

Design

A non-inferiority study.

Setting

England and Wales.

Participants

All primary total and unicondylar knee replacements performed and registered in the National Joint Registry between 1 April 2003 and 31 December 2016.

Main outcome measures

Kaplan-Meier failure function for knee replacement constructs. Failure difference between best performing construct (the benchmark) and other constructs.

Methods

Using a non-inferiority analysis, the performance of knee replacement constructs by brand were compared with the best performing construct. Construct failure was estimated using the 1-Kaplan Meier method, that is, an estimate of net failure. The difference in failure between the contemporary benchmark construct and all other constructs were tested.

Results

Of the 449 different knee replacement constructs used, only 27 had ≥500 procedures at risk at 10 years postprimary, 18 of which were classified as inferior to the benchmark by at least 20% relative risk of failure. Two of these 18 were unicondylar constructs that were inferior by at least 100% relative risk. In men, aged 55–75 years, 12 of 27 (44%) constructs were inferior by at least 20% to the benchmark at 7 years postprimary. In women, aged 55–75 years, 8 of 32 (25%) constructs were inferior at 7 years postprimary. Very few constructs were classified as non-inferior to the contemporary benchmark.

Conclusions

There are few knee replacement constructs that can be shown to be non-inferior to a contemporary benchmark. Unicondylar knee constructs have, almost universally, at least 100% worse revision outcomes compared with the best performing total knee replacement. These results will help to inform patients, clinicians and commissioners when considering knee replacement surgery.
A multidisciplinary approach to the management of NAFLD is associated with improvement in markers of liver and cardio-metabolic health
Authors: Moolla Ahmad , Motohashi Kenzo , Marjot Thomas , Shard Amelia , Ainsworth Mark , Gray Alastair , Holman Rury , Pavlides Michael , Ryan John D , Tomlinson Jeremy W , Cobbold Jeremy F
Published: April 2019

Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent health problem, associated in its more severe forms with increased liver-related and cardiovascular-related morbidity and mortality. We established a multidisciplinary metabolic hepatology clinic in 2014 and have analysed the clinical data to evaluate the effectiveness of this service.

Patients with NAFLD (n=165) who had attended two or more appointments were included. Prespecified clinical data were collected prospectively at clinic appointments and analysed retrospectively. Interventions offered included lifestyle advice, signposting to weight loss services and pharmacological treatment of diabetes and cardiovascular risk factors.

Median follow-up was 13 months (range: 2–34). 59% (n=97) of patients had type 2 diabetes mellitus (T2DM). 53% (n=87) underwent liver biopsy of whom 18% (n=16) had cirrhosis. Median alanine aminotransferase (ALT) reduced by 11 IU/L (p<0.0001), median weight reduced by 3.3 kg (p=0.0005). There were significant reductions in HbA1c, total cholesterol and liver stiffness. Specifically, in patients with T2DM, HbA1c decreased by 4 mmol/mol (p=0.01) with significant reductions in ALT, weight and total cholesterol. Relative cardiovascular risk assessed by the QRISK3 score reduced in the whole cohort and in those with T2DM. Health economic modelling suggested the clinic intervention among those patients with poorly controlled T2DM was cost-effective.

In conclusion, a multidisciplinary approach to the management of patients with NAFLD in this observational cohort study was associated with improvements in liver-related and cardio-metabolic related health parameters and with evidence of cost-effectiveness in patients with poorly controlled T2DM.
Synthetic indicator of the impact of colorectal cancer screening programmes on incidence rates
Authors: Zorzi Manuel , Zappa Marco
Published: April 2019

Objective

The impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.

Design

We defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.

Results

In 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).

Conclusion

The AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.