The Bioinspired Materials conference 2018 was organized for the third time by a team of researchers from Manchester Metropolitan University. This international conference aims to bring together the scientific committee in the fields of biomimetic sensors, bioinspired materials, materials chemistry, three-dimensional (3D) printing, and tissue engineering. The 2018 edition was held at the John Dalton Building of Manchester Metropolitan University, Manchester, UK, and took place on the 10th of October 2018. There were over 60 national and international attendees, with the international attendees participating in a lab tour through the synthetic facilities and Fuel Cell Innovation Centre on the 9th of October. The three conference sessions encompassed a wide range of topics, varying from biomimetic sensors, hydrogels, and biofabrics and bioengineering. In 2016, the first Bioinspired Materials conference was organized by researchers  from Manchester Metropolitan University from within the schools of Science & Engineering and Healthcare Science. The event featured three invited speakers and a poster session, which was attended by fifty local attendees. Due to the great success of the first symposium, the 2017 event was extended to a two-day conference and sponsored by the Royal Society of Chemistry’s Materials Division. This conference, with over 60 international attendees, had internationally recognized keynote speakers and twenty oral presentations. On the first day, there was a dinner and networking event which allowed participants to forge international and multidisciplinary collaborations. Due to the positive feedback received from international visitors, it was decided that the 2018 event would be hosted again at Manchester Metropolitan University. This year’s conference was over the course of two days, with one day of lab tours and a social event for international visitors (including from Japan and Bangladesh) and one day of talks and posters. Therefore, the conference was a perfect mix of local and international visitors with expertise in various areas, ranging from engineering to healthcare, microbiology, chemistry, and material science.Left: Conference logo. Right: Poster session at Bioinspired Materials 2018.In this conference report, we will summarize the key content and topics presented at the conference, with 15 oral contributions (three plenary lectures) and 27 poster presentations in total. The conference was opened by Prof. Patrick Wagner from the Laboratory of Soft Matter and Biophysics at KU Leuven. His research focuses on the use of synthetic receptors, such as molecularly imprinted polymers (MIPs) and surface imprinted polymers (SIPs), for the detection of biomolecules . The useLeft: Invited keynote speaker Prof. Patrick Wagner, with organizer Dr. Marloes Peeters. Right: Dr. Pijush Paul Kumar at the conference.Prof. Mun’de Vestergaard discussed a different bio-inspired technology, the use of membranes, to develop biosensors . BiomimeThe session on hydrogels was opened by an invited plenary lecture of Prof. Alberto Saiani from the University of Manchester . His resThe final session of the conference focused on various aspects of bioengineering. Jane Wood  from ManThere were over 27 presentations covering a range of topics. The 1st prize, sponsored by Fluorochem, was won by Dr. Sachin N. Shah  from theBioinspired Materials 2018 was a great success, and through this conference we were able to bring together a group of diverse multidisciplinary scientists and forge new collaborations. We look forward to continuing with the event and hosting it again at Manchester Metropolitan University in 2019.


Molecules and perhaps offer some speculations about its future.Twenty years—a long time—so what happens after 20 years? Well if you live in New Zealand, according to , if you Molecules, one must go back to the creation of MDPI in 1995, a little before its first issue appeared. That year Dr. Shu-Kun Lin, the company’s current President, who was working at the time at Ciba-Geigy in Basel, Switzerland, conceived the idea of a worldwide center for the collection and sharing of rare chemical samples as a way of preserving chemical diversity for the scientific record. To promote the project, an online journal of synthetic chemistry called Molecules was created and the corresponding ISSN 1420-3049 was obtained. An editorial board was set up with Dr. Lin as Editor-in-Chief and advertisements were published in some of the leading journals of the day to promote the samples collection project [To tell the history of Molecules became one of the first electronic chemistry journals when it was launched with a monthly frequency, in collaboration with Springer Verlag. The University of Basel hosted the first homepage for MDPI at www.unibas.ch/mdpi. Later, MDPI would launch its own server and the website was made available at www.mdpi.org. At the end of 1996, Springer Verlag terminated the agreement with MDPI and sought to continue publication of Molecules under its imprint, which led to a lawsuit between MDPI and Springer over ownership of the journal.Also in 1996 the scientific peer-reviewed journal Molecules, and Volume 2 was published under the direction of Dr. Esteban Pombo-Villar as Editor-in-Chief. The Molbank section of Molecules was introduced in the same year. Molbank publishes papers on synthetic compounds and natural products as one-compound-per-paper short notes; in 2003 the section became an independent journal with its own ISSN (1422-8599). I, the current Editor-in-Chief of Molecules, started working on a part time basis as Editorial Assistant to Dr. Pombo-Villar. Until 2002 when the first staffed Editorial Offices started operations, he would handle from Canada all the manuscript processing duties  for Molecules and some of MDPI’s new journals as they were launched, while Dr. Shu-Kun Lin handled all the actual publishing and administrative tasks.In 1997, after consultation among the members of the International Editorial Board, MDPI took back the publishing of Molecules under its original ISSN until this day, Springer Verlag started publication of a competing journal titled Molecules Online (ISSN 1433-1373), with Prof. Steven Hanessian as Editor-in-Chief. It was discontinued after two volumes in 1999.In late 1998 the dispute between MDPI and Springer was resolved out of court. While MDPI has continued to publish Molecules, replacing Dr. Pombo-Villar whose senior management duties with Novartis no longer allowed him to dedicate appropriate attention to the journal, and I was formally appointed Managing Editor. The start of the new millennium saw in 2000 the brief appearance if a print edition of Molecules. Under the direction of Dr. Francis Muguet and with the kind cooperation of the administration of the École Nationale Supérieure de Techniques Avancées in Paris (France), limited print editions of Volumes 5 and 6 of Molecules, and a few other MDPI journals were produced and distributed to several academic and industrial laboratories [Molecules prepared and hosted from 15–18 July a very successful international conference in Qingdao (China), the International Symposium on Frontiers in Molecular Science 2002 (ISFMS 2002); the journal’s first e-publishing system was set up and the first publishing office outside Switzerland was set up in Qingdao, China with the sponsorship of Ocean University of China [In 1999 Dr. Shu-Kun Lin took over again as Editor-in-Chief of ratories . Also inMolecules, while Dr. Shu-Kun Lin started holding the title of Publisher and Director of the Molecules Editorial Office. During 2005–2006 papers were published in both non-Open Access (non-OA) and Open Access (OA) form, and since 2007 Molecules has published papers exclusively in Open Access form. In 2008 Molecules started adding the Digital Object Identifier (DOI) numbers to each paper using the CrossRef system, the Open Access logo was also added and the copyright line was moved to Creative Commons (CC) “By Attribution” license v.3.0 model. In March 2014 Molecules published its 6000th paper. We would close out our 19th year having published 1301 papers.For the next five years the journal’s steady growth continued. In 2005, the same year the journal celebrated its 10th anniversary , I accepMolecules as Guest editors of Special Issues during the past 20 years, and have shown an interest in the success of the journal. They will be helping with the ever expanding workload of running a major global journal, and we anticipate expanding our sponsorship of some major international conferences and our collaboration with select academic institutions.So what does the future hold for us beyond our 20th anniversary in 2015? To mark the occasion we will be formally announcing in the coming months the addition of a series of Associate Editors selected from among the many world famous scientists who have been active in As we start this important milestone year, I must offer our sincere thanks to our readers and the innumerable authors, anonymous peer reviewers, Assistant Editors at our Editorial Offices in Switzerland and China, and English language editors who have contributed to each and every one of our papers. Without all of you this fantastic journey would never have been possible.


The static and dynamic load-bearing capacities and failure modes of zirconia crowns screwed to multi-unit abutments (MUAs) with and without a titanium base (T-base) were determined. Thirty-six monolithic zirconia crowns screwed to straight MUAs torqued to laboratory analogs (30 Ncm) were assigned to two groups (n = 18). In group A, the zirconia crowns were screwed directly to the MUAs; in group B, the zirconia crowns were cemented to the T-base and screwed to the MUAs. All specimens were aged in 100% humidity (37 °C) for one month and subjected to thermocycling . Afterwards, the specimens underwent static and dynamic loading tests following ISO 14801. The failure modes were evaluated by stereomicroscopy (20×). There was an unequivocally similar trend in the S-N plots of both specimen groups. The load at which the specimens survived 5,000,000 cycles was 250 N for both groups. Group A failed mainly within the metal, and zirconia failure occurred only at a high loading force. Group B exhibited failure within the metal mostly in conjunction with adhesive failure between the zirconia and T-base. Zirconia restoration screwed directly to an MUA is a viable option, but further studies with larger sample sizes are warranted. With thst teeth ,3.Implant-supported prostheses are utilized via two methods of retention; they are either screw-retained or cement-retained. Both modalities have benefits and shortcomings in clinical application . In receThe high demand for aesthetic outcomes, combined with new material technologies and the need for retrievability in implant-supported FDPs, has led to an increased use of screwed monolithic zirconia implant-supported restorations. Usually, this type of zirconia is cemented to a milled titanium sleeve (T-base) and then screwed to the MUA (screwed-cemented type of restoration). This design was suggested by McGlumphy et al. , Rajan aIn contrast to the screwed-cemented restoration, there is another mode of retention of monolithic zirconia crowns to MUAs: Screwing the zirconia directly to the MUA (screwed restoration) without the use of a T-base, thus avoiding the dependence on the cemented joint between the zirconia and the titanium. Although restorations with zirconia crowns attached to MUAs with and without titanium bases are widely used by clinicians, there is no evidence-based data to favor either of these approaches; moreover, no research study has compared the mechanical failure between the two methods. Some believe that the titanium base is vital for the survival of the zirconia restoration, while others are concerned with the detrimental impact of the cement that is placed between the zirconia and the titanium base.The aim of the current study was to compare the static and dynamic load-bearing capacities and determine the failure mode of 3Y-TZP (zirconia) crowns screwed to MUAs with and without a T-base. The null hypothesis was that there would be no difference in either the failure load or the failure mode between the two groups.The stress-number of cycles (S-N) curve results, as well as the failure modes, are presented in Stereomicroscopic examination of the failure mode of all the specimens revealed differences between the groups . Group ANumerous studies have evaluated the fracture strength of different abutments for cemented implant restorations. No available data exists on the fracture strength of screwed implant restorations connected to MUAs, even though these types of restorations have gained popularity with the increased use of immediate loading of multiple implants.The current study compared the static and dynamic load-bearing capacities and determined the failure mode of zirconia crowns screwed to MUAs with and without a T-base, an issue that has not yet been addressed in the literature. Our null hypothesis was partially proven because both groups demonstrated that three specimens survived 5,000,000 cycles, according to International Standard (ISO) 14801, at 250 N. This result may indicate that the two modes of retention (with and without a T-base) have no effect on the mechanical performance of the prosthesis under cyclic loading.The range of human biting forces is 50–300 N in normal chewing as opposed to 175–800 N for maximum voluntary biting forces ,20,21. TOn the other hand, the failure modes differ between the groups. Metal failure (MUA/screw) was demonstrated in both groups; however, in group A (screwed), zirconia failure was also observed, mainly at high loading forces. This pattern was not observed in group B (screwed-cemented). With the latter failure pattern, which included metal failure, most specimens exhibited an adhesive mode of failure between the cement and zirconia. In this study, we used 3Y-TZP, although a newer form of zirconia material with better translucency (5Y-TZP) has been introduced. Research has shown that 3Y-TZP has significantly higher flexural strength than that of 5Y-TZP . Our purThis research was performed according to ISO standard 14801 because the international standard requires that stress is exerted on the implant-abutment-restoration complex in the “worst-case” scenario loading situation . In addiIn the screwed-cemented implant-supported restoration, the impact of oral fluids on the solubility of the luting cement and the retention of the restoration is always of concern. To simulate the oral cavity environment, artificial aging, such as water storage and thermocycling, is performed. In the current study, an aging protocol of storage at 37 °C under 100% humidity for one month, followed by thermal cycling, was conducted. Naumova et al.  and Güng0.5) of the Y-TZP monolithic structure [The failure mode in group B  was expected to be mainly adhesive failure. However, our results demonstrated that at all force levels, metal failure also occurred (screw/MUA). This result is in agreement with the results of other reports ,32,33, wFrom a clinical point of view, separation of the zirconia crown from the T-base, as was found in the screwed-cemented restoration, is easy to repair by re-cementation. Even, metal failure, either of the MUA or of the screw head, is reparable with some cost, by simply replacing the damaged elements. However, when a zirconia fracture occurs, as was seen in the screwed restoration (without a T-base) at high loading forces, the zirconia crown should be replaced, with a higher cost.The limitation of this study was the number of experiments, which was too small for full-scale statistical analysis. However, this study highlighted an importance issue that has not yet been addressed in the literature. Because this is a pilot study, further studies with larger sample sizes are warranted. In addition, similar to other in vitro studies, a laboratory study design cannot fully reproduce clinical conditions, even if the samples are artificially aged by chewing simulation and thermocycling. One might argue that the geometry of the hemisphere with the zirconia coping is different from the geometry of the in vivo zirconia crown. We followed the ISO protocol that simulates the functional loading of an endosseous dental implant and its prosthesis under “worst-case” conditions; however, this method cannot fully predict the in vivo behavior of the dental implant and its prosthesis. Therefore, the results of the present study should be interpreted with caution.Thirty-six straight MUAs  were torqued to laboratory analogs (6 mm width) (Alpha-Bio Tec.) with a digital torque ratchet (30 Ncm) (CEDAR Model DIW 15) and were assigned to two groups (24 specimens per group):® material, Amann Girrbach AG, Koblach, Austria) with a height of 10 mm and a wall thickness of 1.5 mm were designed and milled with an internal ledge for the screw head and then torqued to the MUAs with a digital torque ratchet (25 Ncm) (CEDAR Model DIW 15) (Group A (screwed restoration) (n = 18): Spherically shaped monolithic zirconia copings (Ceramill DIW 15) a.The screwed zirconia cap has an internal zirconia ledge that supports the screw head and is in intimate contact with the MUAs c.® material, Amann Girrbach AG, Koblach, Austria) with a height of 10 mm and a wall thickness of 1.5 mm were designed and milled to fit a titanium sleeve (a T-base) (Alpha-Bio Tec.) (Group B (screwed-cemented restoration) (n = 18): Spherically shaped monolithic zirconia copings (Ceramillio Tec.) b. The ceAll specimens in both groups were stored at 37 °C under 100% humidity for one month, followed by thermal cycling between water temperatures of 5 °C and 55 °C for 20,000 cycles with a 10 s dwell time .After aging, a fatigue test was performed according to the ISO standard 14801 . To compTo determine the static maximum load that the assembly could resist, which corresponds to one cycle on the S-N curve (plotted as force versus log number of cycles), three samples of each group were subjected to an increased static compressive load at a crosshead speed of 1 mm/min until catastrophic failure using a uniaxial universal testing machine . The average failure rate from this test was calculated and defined as the maximal failure load.For the dynamic loading, the remaining specimens were tested in progressively lower loads, starting at 80% of the maximal failure load, using an MTS Systems Corporation machine  . The comDue to the small number of samples, no statistical analysis could be performed with sufficient statistical power.Within the limitations of this pilot study, zirconia restoration screwed directly to an MUA without a T-base is shown to be a viable procedure, and the survival odds of this restoration are not inferior to those of the screwed-cemented restoration. Failure will probably occur within the metal (MUA/screw) before zirconia failure. Further studies with larger sample sizes are warranted.


The reasonable delay time of millisecond-delay blasting using digital electronic detonators can significantly reduce the vibration effects induced by tunnel blasting. This study proposes a method for calculating the delay time for cut holes, easer holes and periphery holes, considering the rocks breaking effect as well as wave superposition theory. And then according to the actual layout diagram of the tunnel holes, the delay time calculation formulas of different holes are put forward. Then the delay times were calculated according to the formulas and applied in the field tests. The velocities, rocks breaking and wave superposition cancellation of the vibration using different delay times are analyzed with digital electronic detonators. Then the optimum delay times of different holes were obtained and applied to New Hongyan tunnel project. The velocity and frequency of the vibration with digital electronic detonators are analyzed, compared with non-electronic detonators. The effects of charge and delay time on the velocity and principal frequency of a blasting seismic wave are discussed. The results indicate that the delay time for the holes must be prioritized to achieve breaking effects in the rock with the simultaneous formation of a new free surface, next considering the wave superposition cancellation. When the delay time of cut holes was 5 ms, the rocks breaking effect and wave superposition cancellation effect both worked well. The velocity of the vibration induced by the cut holes blasting was about only 0.46–0.51 cm/s. When the delay time was 6 ms or much longer, the rocks breaking effect would fail. With regard to the easer holes and periphery holes, the optimum delay time of them were all 5ms. The vertical peak particle velocity was reduced from 2.974 cm/s to 0.901 cm/s with digital electronic detonators. Therefore, the velocity had decreased by 69.70% than non-electronic detonators, which was caused by reducing the single simultaneous explosive charge and setting optimum delay time. The proposed delay time calculation method is demonstrated to be sufficiently accurate and can thus be used as a guideline to reduce tunnel blasting vibrations. Complex environmental tunnels that pass through dense buildings are constructed using the drilling and blasting method are becoming increasingly popular ,2,3. TunWith the development of high-precision digital electronic detonators, fine controlled blasting has been successfully applied to the construction of complex environmental tunnels. Digital electronic detonators achieve accurate millisecond delay by using an integrated circuit chip. The scope of the delay time is approximately 1 ms to 16 s, and the delay error is only approximately 0.1 ms. Digital electronic detonators can accurately achieve time delay ignition according to the needs of the conditions on site. A strong rock-crushing effect can be obtained using digital electronic detonators, and damage to structures near the tunnel induced by tunnel blasting under complex environmental conditions can be reduced ,13. Moret = T/2(T is the vibration wave period) that allows the majority of borehole vibration to cancel each other out under the invariable blasting vibration cycle and the same vibration waveforms. Hinzen [T/3 <Δt <2T/3 (T is the vibration wave period), the two seismic waves can reach interference cancellation to different degrees. Wang [When tunnel blasting is performed using digital electronic detonators, the blasting vibration can be effectively reduced by setting a reasonable delay time to ensure millisecond delay blasting. The vibration can be further reduced by using a method in which crests and troughs are superposed onto each other or by using a staggered wave crest (or trough)  and trou. Hinzen  found th. Hinzen  and Hosh. Hinzen  proposed. Hinzen  used a t. Hinzen  develope. Hinzen  achieved. Hinzen . The tim. Hinzen  proposed. Hinzen  found thes. Wang  demonstres. Wang  considert in this paper was first proposed by literature [The optimum delay time terature  in 1962,In the tunnel blasting, the holes are composed of cut holes, easer holes and periphery holes. The calculation method of delay time is supposed to determine according to the types of holes. Firstly, the importance of the breaking effect is emphasized for the holes. Considering the rocks breaking effect of holes, the method of delay times in quarries blasting are used for tunnel blasting. Next, the wave superposition cancellation effect is considered in the calculation of the delay time. The two seismic waves can achieve good interference cancellation when the delay time is half period of the vibration, according to U. Langefors’ theory. The delay times are determined based on both rocks breaking effect and wave superposition cancellation effect. Finally, the calculated delay times are checked and obtained by field tests. In one word, the delay time is determined by combination of rock optimum breaking effect, wave superposition cancellation effect and field tests adjustment, and the delay time are calculated including the rock’s physical, mechanical and construction parameters according to the actual blasting holes, which are the novelty in this paper.In order to determine the optimum delay time of different blasting holes, the holes are firstly classified into two types: 1) cut holes and 2) easer holes and periphery holes. The theoretic calculation methods for above two kinds holes are put forward. And then according to the actual holes layout diagram, considering the rocks breaking effect as well as wave superposition theory, the delay time formulas of different holes are studied. Then the delay times were calculated according to the formulas. The different delay times were checked in the field tests in order to find the optimum time and to prove that the calculation method is feasible. The velocity, rocks breaking effect and wave superposition cancellation of the vibration induced by different delay time tunnel blasting are analyzed. The optimum delay time is determined by theoretical analysis and field tests. Finally, the methods of delay time using digital electronic detonators are applied into the actual tunnel, the velocity and frequency are analyzed comparing with that of tunnel blasting using non-electric detonators. The relationships among the vibration velocities, dominant frequency, single initiation charge and electronic detonator delay time are discussed. This work aims to provide the calculation methods of different holes for design of the tunnel blasting construction and reduction of the vibration effect.The basic information of the tunnel  is as foThere are many theories of millisecond delay time calculation for tunnel blasting, such as the method of short delay blasts in quarries considering the breaking effect of rocks , the U. Before cut hole blasting is performed, there is only a free surface in the tunnel. After the cut hole blasting, additional free surfaces for subsequent blasting are successfully created. Thus, the peak particle velocity is mainly caused by the cut hole blasting. The vibration caused by easer holes and periphery holes is often smaller than that resulting from cut hole blasting. Therefore, the key requirement to reducing tunnel blasting vibration is to control the vibration induced by cut hole blasting.The blasting vibration of cut holes can be reduced through hole-by-hole blasting using digital electronic detonators. The key point is how to set the delay time for the cut holes. If the delay time of hole-by-hole blasting for cut holes is overly long, the breaking effect of rock will fail. Alternatively, if the delay time of hole-by-hole blasting for cut holes is not sufficiently long, several cut holes may initiate simultaneously, leading to a high vibration due to the difficulty of forming new free surfaces and the lack of wave superposition cancellation. Therefore, the delay time of hole-by-hole blasting of cut holes must be calculated considering the breaking effects in the rock simultaneously with the formation of new free surfaces and wave superposition cancellation. Therefore, the delay time for cut holes must be sufficiently long to fully develop the fractures between the first charge and the outline of the rock medium and form a new free surface. Moreover, the delay time for cut holes is based on the fact that the entire rock mass in the vicinity of the first charge is still in a stressed condition to enhance the rock break up when the second charge explodes.t was first proposed by literature [t1 is the time that the rock medium obtains the stress state induced by the first charge package explosion, that is, the time required for the stress wave to be returned from the charge center to the surface and then from the surface back to the charge center, as shown below.The optimum delay time terature  in 1962.w is the resistance line (m) and cp is the longitudinal wave propagation velocity (m/s).Here, t2 is the time from the development of the fracture to the formation of the outline of the thrown rocks on the fracture surface. The shape of the thrown fragments of rocks is different under different conditions. In this paper, we consider a thrown body that is elliptically cut through the hole, as shown in t2 can be expressed asutr is the rate of propagation of fractures in the homogeneous medium under a unit charge consumption (m/s), κ is the rupture coefficient of the medium, a constant, and β is the angle of the prism of the thrown body (°).t3 is the time that the fracture surrounding the prism of the thrown body extends to a sufficient width corresponding to the newly formed free surface. Test results have shown that the width can reach 10 cm while the second cut hole explodes. The pressure in the first cut hole ensures that the rock medium remains in a stressed condition. t3 can be expressed asT3 accounts for the effects of certain parameters not present in the equation that appear in the equation of motion; as a first-order approximation, T3 = 8×10−5, a constant. This parameter can be determined more precisely by performing blasting tests. ϕ is the hole diameter (cm), ρ is the density of the rock (g/cm3) and S is the area of the thrown body (m2).2)ϕ=T3ρSϕIn Eq . The period of the P wave is taken as 4 times  follows :T=4ΔT=4PKT is the periodic constant of the P wave associated with rock properties, a constant, and W is the single initiation charge (kg).In Eq no The front view of the wedge-shaped cutting of the tunnel through blasting holes is shown in Hi refers to the resistance lines of different rows of holes. The maximum resistance line Hi and the depth Li of the different blast holes was calculated according to the geometrical relationship between different blast holes; based on their relationship, the reasonable delay time was calculated. The relevant equations used for these calculations are as follows:i is the row number of the blast holes, and Hi is the resistance line of different rows corresponding to the holes used to calculate the time ti1. L is the length of tunnel excavation in feet, and Li represents the depth of different rows of holes used to calculate the time ti2. X0 is the distance from the bottom of the cut hole to the center of the section, X1 is the horizontal distance between the bottom and the end of the cut hole and X2- X6 are the distances between the blasting holes, as shown in ti1 and ti2 can be expressed as shown below.In ti3 was calculated as follows:By calculating the volume and weight of the discarded rock, the time tzi yields the following equation:Si is the area of the discarded rock of each hole (m2), ρ is the rock density (g/cm3), ϕ is the hole diameter (cm), and tzi is the total millisecond delay time for tunnel blasting (ms).Adding Eq  to Eq 1 to obtaicp, the density of the rock ρ, the rock propagation velocity in the fracture utr and the rock fracture capacity coefficient κ. Second, the relevant blasting construction parameters, such as the maximum resistance line Hi, the depth of the blast hole Li, the distance Xi and the diameter ϕ of the blasting holes, must be determined. The accuracy of the millisecond delay time is directly related to the accuracy of the geotechnical and construction parameters.Eqs –19) ena ena19) eThe field tests of tunnel blasting were performed in the New Hongyan Tunnel. The excavation footage of the tunnel was 2 m. The blasting method using non-electric detonators was applied to construct this tunnel, and the total blasting charge was 88 kg. The upper steps were divided into two blasts, I and II, as shown in The houses are located above the tunnel. Monitoring points A and B were each monitored using a UBOX-5016 tester made by TDEC Measurement and Control Co. Ltd in Chengdu, China, and the distance from the explosive source was approximately 28.83–29.97 m, as illustrated in According to The top view of the tunnel hole layout was drawn, as shown in The blasting parameters, such as the blasting hole arrangement and total charge, remained unchanged. The length of the tunnel excavation was 2 m. The considered total number of holes was 130, and the total charge was approximately 88 kg. Among the blast holes, there were 12 cut holes with a single-hole charge of 1.4 kg.ρ = 2.61 g/cm3. The formula is as follows:The natural density of rock was measured by means of measuring volume method. The density test results of rock are reported in ρ is the density of the rock, m is the mass of the rock and V is the volume of the rock.In the above equations, cp = 4500.27 m/s. The standard tested specimens were fixed on the test frame. The transmitters set on the ends of tested specimens. In addition, they should cross the center line of tested specimens and measured the distance between the two transmitters. The transmitters should bear 0.05 MPa compression pressure and measure the velocity of longitudinal and transverse wave transmitted in the tested specimens. The rock acoustic measurement test was shown in The velocity of longitudinal wave was obtained by rock acoustic measurement test as Vp is the velocity of longitudinal wave of the rock, L is the length of the tested rock specimens (mm), which is the distance between sending and receiving probes, tp is the propagation time of the longitudinal wave (μs), to is the no time delay of instrument system (μs).In the above equations, utr = 1600 m/s with κ = 0.65. According to the engineering survey data and research reports, ϕ = 4.2 cm, S1 is calculated by S1 = 2.24 m2. The millisecond delay times of the cut holes is reported in According to the theory of fracture mechanics, the maximum speed of fracture propagation is no more than 0.38 times the compressional velocity . The speAs shown in As shown in In There are 62 easer holes with a single hole charge of 0.6–0.8 kg; 44 periphery holes with a single hole charge of 0.4 kg and 12 bottom holes with a single hole charge of 0.8 kg.t1+t2+t3, the period T of the P wave also needs to be calculated. According to Eq no PKT = 0.0032, the period Ta of the easer holes can be calculated asRegarding the delay time for the easer holes and periphery holes, in addition to calculating the delay time of Tp of the periphery holes:The period The millisecond delay times of the easer holes and periphery holes are presented in The delay time of the easer holes and periphery holes is estimated as 4–6 ms. Combined with the experiment of cut holes in the field, the optimum delay time of the easer holes and periphery holes is 5 ms. The delay time of bottom holes is also 5ms according to the periphery holes.The layout of the tunnel blast holes and delay times is shown in From In the near-blasting field of shallow tunnels, the P wave is the main carrier of a blasting seismic wave because P wave vibrations have a high frequency and large peak particle velocity. The peak particle velocity of a P wave is proportional to ifferent . Further[(W3)1.7 . Therefo[(W3)1.7 :Vp=pKV(VP is the peak velocity of the ground surface caused by P waves (m/s), VS is the peak velocity of the ground surface caused by S waves (m/s), PKV and SKV are the factors related to the geological blasting method, the geological conditions and other miscellaneous factors, W is a charge or detonating charge (kg), and R is the distance between the measuring point and the center of the blasting source (m).In the above equations, n of the non-electric detonator charge (n refers to the number of simultaneous blasting holes). Therefore, the reduction in the peak particle velocity mainly occurs because the digital electronic detonators decrease the charge amount per delay considerably. According to Eqs no For each particular tunnel, the geological conditions of the rock formation, depth and geological parameters cannot be changed. The blast-holes are initiated using electronic detonators for each hole, with an initiation charge of 1/T of the P wave is proportional to W1/6. Furthermore, Meng [f changes with the charge and distance as follows:As discussed in section 4.1, the main carrier of a blasting seismic wave is the P wave. The period re, Meng  considerα1 and α2 are constants and R is the distance from the center of the blasting.In the above equations, W1/6, and in the latter, the period is proportional to W1/3. The two equations demonstrate that using electronic detonators to achieve hole-by-hole initiation can reduce both the charge of single detonation and vibration wave period and increase the dominant frequency of the blasting vibration wave.Without considering the propagation distance of the seismic waves, Eqs no The delay time using electronic detonators directly affects the single detonation charge. Therefore, the delay time will affect the peak velocity and vibration frequency of the blasting seismic wave. There are three main situations:(1) When the delay time of the electronic detonator is set less than the reasonable delay time calculated by Eq no (2) When the delay time of the electronic detonator is set longer than 3 to 5 times the vibration period, the tunnel blasting can achieve single-hole charge interval initiation without wave superposition. Each single-hole blasting vibration wave maintains its independence. In this case, the peak velocity and frequency of each hole interval detonation is taken as single-hole charge blasting.(3) When the delay time of the electronic detonators is longer than the reasonable delay time calculated by Eq no This study developed a method for calculating the delay time for tunnel millisecond delay blasting using digital electronic detonators and investigated the influence of charge and delay time on the peak velocity and dominant frequency of the blasting seismic wave through a case study of a tunnel blasting project. The following conclusions are drawn from this research:(1) The delay time for the holes must be prioritized to achieve breaking effects in the rock with the simultaneous formation of a new free surface, next considering the wave superposition cancellation. The optimum delay time of cut holes was 5 ms, and the rocks breaking effect and wave superposition cancellation effect both worked well. The velocity of the vibration induced by the cut holes blasting was about only 0.46–0.51 cm/s. The optimum delay time of the easer holes and periphery holes were all 5ms.(2) The method of calculating the delay time was applied in New Hongyan tunnel with digital electronic detonators. The vertical peak particle velocity was reduced from 2.974 cm/s to 0.901 cm/s with digital electronic detonators. Therefore, the velocity had decreased by 69.70% than non-electronic detonators.(3) Through the incorporation of the results from the field test, the delay time calculation method for tunnel blasting using electronic detonators achieved desirable results in reducing vibrations induced by tunnel blasting. Furthermore, the accuracy and credibility of the electronic detonator delay calculation method for tunnel blasting were confirmed.


When I recently made the decision to step down as co-Editor-in-Chief of PLoS Pathogens, it gave me the opportunity to look back over the past 15 years since the first EIC of PP, John Young, asked me to join the PLoS journal as an Associate Editor. Back then, I couldn’t spell OA, let alone appreciate the seismic changes that the Open Access revolution would play in the communication of science. When the original founders of PLoS  proposed the new concept of the Creative Commons Attribution License back in 2004 that permitted the unrestricted use, distribution and reproduction of properly cited scientific work, the historical arc of scientific research publication was fundamentally inflected. What has transpired has included the good (wider access to scientific research by anyone with an internet connection), the bad  and the ugly . Regardless, there is no question that OA is now fundamentally key to the future of scientific publication.For me, the realities of shrinking professional bandwidth forced me to conclude that I could no longer balance all of my other ever-growing duties with the time the PP co-EIC job deserves. The realities of shepherding a new biotech start-up company, OncoMyx, as well as trying to maintain funding for an independent, curiosity-based research lab in an era when the average PI needs to write 10 grant applications in order to get one funded, simply have come home to roost. But to balance my own angst of departing a journal that I have come to love dearly, I was more than thrilled to learn that my new replacement is Mike Malim, who is the perfect person to help lead the journal into the future. Welcome aboard, Mike!There are a lot of people I want to thank from the PLoS family, both past and present. It takes a really big village to raise and sustain a journal like PP, a fact that is evident when you consider just the size of the PP Scientific Board of Editors: 65 Section Editors, 176 Associate Editors, 37 Frontmatter Editors, plus hundreds of invited Guest Editors over the years, all of which is managed by our core group of journal staff members. Of the many PP journal staffers I have worked with from the past, there are too many outstanding individuals to list but there are a few names I would never forgive myself for not including in a deserved shout-out: Catherine Nancarrow, Mary Kohut, Cory Mann, Laura Ray, Lily Berrin, and Sarah Sarber all made the day-to-day tasks of running the journal business a constant pleasure. The current PP staff roster continues that tradition of excellence, and Mike inherits a tremendous team that includes Eileen Clancy, Rebecca (Becs) Kirk, Claire Turner, and Rebecca Barilla. This is an exciting and transitional phase for all of the PLoS journals, and one of the things I will miss most is our regular meetings with the EICs of the other PLoS sister journals (you know who you are!) and with the newly constituted PLoS Board of Directors, led by Alison Mudditt. I especially want to make a very special thanks to Veronique Kiermer, Executive Editor, who continues to expertly steer the entire PLoS family from the past and into the future. Good show, Veronique! Finally, I want to thank my PP EIC partner-in-crime, Kasturi Haldar, for helping to oversee the journal with me for these past years. Kasturi, it has been an honor to work with you.As numerous philosophers have opined , it is difficult to make predictions, especially when they are about the future. But it is fair to say that as science evolves, scientific communication and publication must as well. In the case of PP, the focus of the journal has traditionally been on pathogenesis caused by identifiable pathogens, but perhaps future articles will give some much-deserved attention to commensals and microbiota that may not be directly pathogenic. When new areas emerge, PP has always been receptive to promoting them, and I suspect this will remain a core principle moving forward. Issues such as these are now in the hands of the new PP team, and I have no doubt that their decisions will be the right ones.GMcF December, 2019


Exotic compact objects with physical surfaces a Planckian distance away from where the horizon would have been are inspired by quantum gravity. Most of these objects are defined by a classical spacetime metric, such as boson stars, gravastars and wormholes. We show that these classical objects are gravitationally unstable because accretion by ordinary and dark matter, and by gravitational waves, forces them to collapse into a black hole by the Hoop conjecture. To avoid collapse, either their surface must be a macroscopic distance away from the horizon, or they must violate the null energy condition. The recent discovery of gravitational waves –5 has trOne such hint is the possibility that massive compact objects may seem like black holes but may not actually be black holes because they may lack an event horizon. Such black hole mimickers are called Exotic Compact Objects (ECOs) , 17, andAlthough precisely understanding how ECOs form and how generic their formation is remains unclear, they have been a playground for theorists to explore how gravitational waves could be used to distinguish between the coalescence of black holes and that of other exotica and to detect signatures of quantum gravity at horizon scales. One such signatures concerns tidal Love numbers, which characterize the degree of deformation of an object in the presence of an external tidal field , 22. WheAnother signature concerns echoes –29. Let How realistic are ECOs and how seriously should one take such alternatives? This is a difficult question to answer, because there are no field equations whose solution leads to these objects. One can of course concoct a carefully designed spacetime, and then insert it into the Einstein equations to compute the stress-energy tensor that leads to such a metric. But at least in General Relativity, such stress-energy tensor will violate the energy conditions. Without field equations one can also not answer whether the generic collapse of matter leads to the formation of such objects. But at the very least, one must demand an unconditional requirement: stability.Ultracompact objects that lack an event horizon typically suffer from instabilities.We here focus on the stability of ECOs against gravitational collapse due to interactions with their medium, and show that they generically encounter insurmountable obstacles that prevent them from having a surface too close to their would-be horizons. This, in turn, places a theoretical maximum on their gravitational compactness that limits how similar to black holes they can be. If this limit is broken, we show that ECOs collapse to BHs during, or even before, they enter the inspiral phase of coalescence. These obstacles render ECOs, and their subsequent echoes, theoretically unfavored.The obstacles described above rely on Thorne’s Hoop conjecture , 38, whil system , 40, coll system , non-timl system , collidil system , chargedl system , and evel system . The conl system , trappedl system , Birkhofl system , and thel system .T is simply R is the ECO radius,Let us then assume that ECOs are immersed in a medium that forces them to gain mass, while maintaining their radius approximately constant, as is the case for neutron stars.ollowing , and theECOs, if they exist, are not alone. Like everything else in the Universe, ECOs should be surrounded by dark energy, dark matter, an intergalactic medium and an interstellar medium. Let us then calculate how much mass-energy ECOs accrete from these media.Given that ECOs would be completely immersed in these media, we can model their accretion through the Bondi–Hoyle framework. We assume then that the accretion rate is given by (see e.g. –56)4\docc the speed of light [Let us now apply this accretion rate to matter in the interstellar, intergalactic and intracluster medium. The interstellar medium consists of gas in various forms that fills the space between stars in a galaxy. The density is of light . Using t1,10-5)c , and a c-27kg/m3 . Using tthors of , who stu31)kg/m3 , 62, whiLet us now consider the ECO accretion of dark matter. The density of dark matter depends strongly on the type of galaxy or cluster the ECO lives in. Supermassive ECOs, like supermassive black holes, are expected to live in galaxy cores, since they would sink to the center through dynamical friction. The local mass density of dark matter in our galaxy is about -21kg/m3 , but nea profile ). Using eference  has showOne may also wish to consider the accretion of cosmic microwave background (CMB) radiation and dark energy into ECOs. Following the cluster plus black hole model of , one fintidal heating) during the early inspiral of a coalescence event, and the same tools are applicable to ECOs with absorption efficiency k. Consider then an ECO in the early quasi-circular inspiral, where velocities are small and fields are sufficiently weak that the post-Newtonian approximation holds [v is the orbital velocity, and Even if ECOs were completely alone in the Universe, their mass would still increase due to the absorption of the gravitational waves they emit when in orbit around each other. Perturbation theory allows us to estimate the amount of mass-energy absorbed by a black hole , we assume the Bondi-Hoyle rate is constant to find on years , 31  of these processes force the ECO to have a minimum radius that is many orders of magnitude larger than a Planck length from its would-be horizon. Using Eq. , we findFrom the above minimum radii one can calculate the maximum compactness of an ECO relative to that of a black hole. Using Eq. , we findWe have shown that ECOs cannot have a surface anywhere near a Planckian distance away from their would-be horizons, if they are to avoid collapse into black holes due to accretion by the interstellar medium, intergalactic medium, dark matter accretion, or gravitational wave absorption when in a binary. This result has strong implications for the search of ECOs with tidal Love numbers , 22 or wCan one circumvent these no-go results? The easiest way to do so would be to argue that the Hoop conjecture does not apply to ECOs, the classical ones we studied within the context of standard General Relativity, for some reason. This is somewhat hard to believe, since this conjecture does not rely on the particular form of the field equations. Nonetheless, one could argue that violations (though never observed) could be possible if one allows for forms of matter that do great violence to the energy conditions. If so, one would then have to explain where this strange matter came from in the first place, and how it interacts with all other astrophysical observations. Another way to bypass the no-go results is to argue that the ECO surface is not fixed, but rather it increases as its mass increases. This indeed occurs for black holes because their area is proportional to their mass squared. However, the surface of ECOs have so far been theorized to be rigid for most of the individual examples that exist in the literature. For instance, gravastars (ECOs with a de Sitter interior and a Schwarzschild exterior) possess a thin but rigid shell with an extremely stiff equation of state . DynamicThe purpose of our analysis is not to discourage the open-minded scientific inquiry of theoretical possibilities that are not observationally excluded, but rather to point out that some of these possibilities are theoretically excluded on the basis of stability. Ultimately, rather than investigating observations that may reveal the presence of an ECO, it may be more worthwhile to cement the foundations of classical ECO theory from an action-principle stand point, thus allowing for the investigation of whether these ECOs can form dynamically in nature from gravitational collapse or not. Lacking this, ECOs remain a theoretical possibility that is currently more rooted in our imagination than in reality.


The editors, members of the editorial board, publishers, reviewers, authors, and all other entities related to the Euroasian Journal of Hepato-Gastroenterology are extremely happy as the articles of the journal are now referred in PubMed. This is in addition to its indexing in several other indexing organizations. Our thanks and gratitude are for all who have been working for this important endorsement and those who worked for this purpose.Indexing of journals in PubMed is not the only and final target of the editors and publisher. The journal should be placed in better position by having an impact factor within a reasonable time. To achieve this goal, some fundamental changes would be incorporated soon.The journal will act as an official journal of the Euroasian Gastroenterological Association (EGA). A strong executive committee of EGA would constantly look after the journal.The editorial board of the journal will be strengthened and formulated to meet the demand of the time. The instructions to authors will be made more objective-oriented and the authors will get better review process for their precious article.The numbers of issues of the journal will be extended from the present levels of two per year. All these efforts would finally make this journal one of the most prestigious journals in this region. We all are expecting your active cooperation to accomplish this goal.We are extremely glad of the work and collaboration of the publisher of the journal, JAYPEE Publisher, for their outstanding support in the last 7 years and hope that these scholastic and materialistic support would be provided for years to come.Finally, we would remind that a journal is an outcome of a team work and we do hereby express our gratitude to all seen and unseen entities related to journal compilation and publication.Sheikh Mohammad Fazle AkbarEditor-in-ChiefEuroasian Journal of Hepato-GastroenterologyHasan OzkanEditor-in-ChiefEuroasian Journal of Hepato-GastroenterologyMamun Al-MahtabCo-Editor-in-ChiefEuroasian Journal of Hepato-Gastroenterology


Organ donation after brain death (DBD) is the standard strategy for organ transplantation; however, the concept of brain death is not universally accepted due to cultural beliefs and barriers amongst billions of people worldwide. Hence, a novel donation pattern has been established in China which outlines the concept of donation after brain death followed by circulatory death (DBCD). Differently from any current donation classification, this new concept is formulated based on combination of recognizing brain death and circulatory death. Should approval be gained for this definition and approach, DBCD will pave a novel donation option for billions of people who cannot accept DBD due to their cultural beliefs.A multi-center, cohort study was conducted from February 2012 to December 2015. 523 kidney transplant recipients from four kidney transplant institutions were enrolled into the study, of which, 383 received kidneys from DBCD, and 140 from DBD. Graft and recipient survivals following transplantation were retrospectively analyzed. Postoperative complications including delayed graft function,, and acute rejection, were also analyzed for both groups.P = 0.32 and 0.86,respectively). One-year graft and recipient survivals were equal between DBCD and DBD groups . Furthermore, DBCD did not increase incidences of postoperative complications compared with DBD, including delayed graft function  and acute rejection . Additionally, antithymocyte globulin as induction therapy and shorter warm ischemia time decreased incidence of delayed graft function in DBCD group .DBCD could achieve comparable graft and recipient survivals in comparison with DBD (Log-rank Kidney donation through DBCD achieves equally successful outcomes as DBD, and could provide a feasible path to graft availability for billions of people who face barriers to organ donation from DBD. Kidney transplantation is currently the preferred treatment mode for patients with end-stage renal disease . AlthougIn the light of cultural barriers, efforts to promote DBD in China have not been satisfied from 2009 . Hence, This was a multi-center, retrospective, observational cohort study involving 523 kidney transplants from DBCD or DBD from February 2012 to December 2015. The transplants were performed in four institutions: The Third Affiliated Hospital of Sun Yat-sen University, The First Affiliated Hospital of Jilin University, The Second Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, and The Third Affiliated Hospital of Guangzhou Medical University. Of the 523 kidney transplant recipients enrolled, 383 received DBCD and 140 DBD.Donors were selected based on confirmed patient identity, age ≤ 65 years, no history of kidney disease, drug abuse or uncontrollable psychotic symptoms, no active infection including HIV, bacteria or fungus, no history of uncontrolled hypertension, diabetes mellitus with complications, no history of malignant melanoma, metastatic or incurable malignancy .No organs from executed prisoners were used in the study, and procurement of kidneys from all donors was conducted in accordance with the Declaration of Helsinki and Istanbul Declaration, and approved by the Human Organ Transplantation and Ethics Committee of each institution. The donation types were determined by donors’ families, who also signed consent forms that were approved by the Ethics Committees of each institution. The Ethics Committees were established according to the Operational Guidelines for Ethics Committees that Review Biomedical Research developed by the World Health Organization, and consequently included physicians, lawyers, statisticians, paramedical personnel, and laypersons . Organ a2 with a velocity of 6 L/minute was added to patient via tracheal intubation for 8–10 min. Breathing movement should be closely observed and arterial blood gas analysis should be tested finally. The cessation of spontaneous respiratory function was defined as no breathing movement with PaCO2 equal or greater than 60 mmHg or a rise of 20 mmHg more than basal level. The brain death of each donor was adjudicated independently by two neurologists or neurosurgeons [The definition of brain death was strictly determined by the exclusion of confounders, as well as the presence of three essential findings; namely, irreversible coma, absence of spontaneous motor activity, and the absence of all brain-stem reflexes. To determine the cessation of respiratory function, an apnea test should be carried out before declaration of brain death as follows: after mechanical ventilation and vasopressors withdrawn, 100% concentration of Osurgeons , 11.Cardiac death was legally defined as irreversible cessation of circulatory function, based on definitive proof by confirmatory tests, such as electrocardiography, intra-arterial monitoring or Doppler ultrasound. An observation period of 5 min was also employed, to ensure the irreversibility and permanence of the patient’s cardiac death .Organ donation and recovery was conducted by organ procurement organization established by the National Health and Family Planning Commission of China. DBDs were procured after declaration of brain death according to the aforementioned diagnostic criteria. For DBCDs, following determination of brain death, written consent was obtained from the donor’s immediate family, agreeing to donation of the kidney and withdrawal of life support. The obtained consent for donation was then reported to the Organ Donation Committee, which supervised the DBCD process.Donors were monitored with invasive blood pressure sensors in the operating room. Following condolences, mechanical ventilation and vasopressors were withdrawn, and vital signs were continued to be monitored. The definition of cardiac death was determined according to the aforementioned criteria, and after 5 min of observation following cardiac arrest, death was declared and organ recovery initiated. According to the national guidelines in China, warm ischemia time was recorded from the termination of life support to the hypothermic perfusion of graft, and cold ischemia time was recorded as the duration from hypothermic perfusion to blood reperfusion during transplantation surgery. The warm ischemia time of the kidney grafts was limited to under 60 min . Zero-tiEither antithymocyte globulin (ATG) or basiliximab was administered as induction therapy. Additionally, methylprednisolone (500 mg/day) was continuously administered intravenously during the first 3 days postoperatively. Maintenance immunosuppressive regimens consisted of a calcineurin inhibitor, mycophcnolate mofetil, and prednisone. Myeophenolate mofetil initiated immediately after transplantation was maintained at a daily dose of 1.0–1.5 g. Tacrolimus or cyclosporine was started on Day 2–4 at 0.1–0.15 mg/kg/day or 6–8 mg/kg/day, respectively, according to the level of recovery of renal graft function. The immunosuppressive regimens were adjusted to achieve target therapeutic trough levels in peripheral blood. Oral administration of prednisone, initiated at 30 mg/day on Day 4 following transplantation, was reduced by 5 mg every week to a maintenance dose of 10–15 mg/day.;: 0–1 of six possible mismatches, 2–4 mismatches, and 5–6 mismatches [Postoperative complications such as incidences of DGF, primary non-function (PNF) and acute rejection (AR) were retrospectively analyzed in this study. The definition of DGF in our study is the use of dialysis in the first postoperative week, or failure of serum creatinine to decrease by 10% in the first 48 h following transplantation . PNF wassmatches . PositivAll recipients were followed up and routine tests as well as concentration of calcineurin inhibitors were regularly assessed. Graft and recipient survivals were also analyzed. Follow-up of a patient ceased upon the patient’s death, PNF, resection of the transplanted kidney or secondary transplantation due to complications arising from the first.P values less than 0.05 were considered statistically significant.Baseline characteristics of recipients and donors as well as postoperative complications between the two groups were compared using the t-test for continuous variables or the chi-squared test for discrete variables. Kaplan–Meier curves were plotted to depict graft and recipient survivals, and a curve comparison was performed between the two groups using the log-rank test. Incomplete data entries were not included in our analyses. Risk factors for survivals were studied using a cox regression regression analysis. All analyses were performed with Statistical Package for Social Science 22.0 for Windows . P > 0.05) (Table P > 0.05). Although no significant difference was found in mean age between two groups, 59.8% of DBCD donors were older than 40 years, compared with 12.1% of DBD donors (P < 0.05). A significant difference was found in the causes of death and a significantly greater proportion of DBD donors died from cerebral trauma than DBCD donors . Likewise, a significantly greater proportion of DBCD donors died from cerebrovascular accident than DBD donors . The warm ischemia time of DBCD donation was 16.2 ± 5.2 min, with a range of 9 to 35 min. Among different groups of warm ischemia time, 57.8% donors had warm ischemia time 10-20 min. No significant difference was found in cold ischemia time between the two groups .In this study, 199 DBCD and 85 DBD donors were included. There was no significant difference in gender, use of vasoactive drugs, cardio-pulmonary resuscitation, intensive care unit time, body mass index and serum terminal creatinine between the two groups  (Table P = 0.78). All the positive PRA recipients in the two groups were classified into 10–50%. Regarding induction therapy, 291 recipients (76%) in the DBCD group received ATG compared with 39 recipients (27.9%) in the DBD group (P < 0.05).No significant differences were found between recipients from the two groups for most baseline characteristics (5) Table . The majP > 0.05; Table P = 0.46). Five recipients in DBCD group developed PNF, but none from DBD group (P = 0.33). However, all the five grafts with PNF were confirmed with severe glomerulosclerosis by zero-time biopsy. ATG was found to be related with lower incidence of DGF in comparison to basiliximab in the DBCD group . Additionally, 9.1% cases from DBCD group suffered from AR compared with 8.6% in DBD group (P = 1.0). According to a previous published study, we divided warm ischemia time into two groups: ≤18 min and > 18 min [. . Of 383 recipients, 101 patients (26.4%) received grafts with WIT > 18 min, of whom there were 27 patients (26.7%) suffered from DGF . Incidences of PNF and AR were also higher in the > 18 min group; however, no significant difference was found . Serum creatinine levels were recorded at different follow-up time points, and no significant difference was found in serum creatinine curves between the two groups (P = 0.08).There was no significant difference in postoperative complications between the two groups . In DBCD group, five patients had PNF, five severe bleeding and three renal allograft ruptures postoperatively and resected transplanted kidneys, whereas four patients had severe bleeding, two renal allograft rupture, one peri-renal abscess, and one severe AR from DBD. Regarding recipient survival, seven from DBCD group died from severe pneumonia or cardiovascular disease, and three from the DBD group died from severe pneumonia or myocardial infarction.The median follow-up time for graft and recipient was 25 months . Graft survival in DBCD group was comparable to DBD group (P > 0.05).The cox regression regression analysis showed that no characteristics of recipients and donors in this study affected graft and recipient survivals following kidney transplantation from DBCD and DBD  as well as AKI, all of which inevitably exert adverse effects on graft and recipient survival, and increase incidences of DGF and PNF , 22, 23.A standard protocol defines the approval criteria for DBCD. Before declaration of brain death, an apnea test should be carried out to determine whether autonomous respiration exits. The test should be terminated if cardiac arrhythmia, decline of oxygen saturation and blood pressure are observed. In order to limit warm ischemic time, cardio-respiratory support should be withdrawn in the operating room after all necessary preparations have been completed, and the retrieval team and operating room staff should be ready in advance . ATG is P < 0.05), this may be attributed to the more conservative view held by older people in China regarding brain death, and the understanding of younger generation in DBD. Interestingly, a significantly higher proportion of DBCD donors died from cerebrovascular episodes. Age of a donor may have influenced this, as older people are potentially at a higher risk of developing cerebrovascular events.Through comparison of donor baseline characteristics, 59.8% of DBCD donors were identified to be older than 40 years, compared with 12.1% of DBD donors (Information about the long-term outcome of DBCD was not available in our study due to the limited time since which this novel donation pattern had been established. Additionally, more accurate measurement of warm ischemia time of DBCD should be ensured, which could account for the unexpected finding that PNF and AR were higher in the > 18 min group, although no significant difference was found. Warm ischemia time was reported no effect on graft outcome which may be attributed to insufficient samples size and inability to detect this effect , 31. ThuDBCD, a novel donation approach, provides an acceptable outcome in terms of both survival and postoperative complications, and should be regarded as equivalent to DBD. The benefits of DBCD largely arise from its controlled procurement process of grafts which reduces the risks of warm ischemia injury. The controlled processes of DBCD should therefore be strictly followed.In conclusion, although DBD is currently the standard strategy for organ transplantation, our findings suggest that DBCD is a viable option to provide graft availability to renal transplant patients. In view of the large numbers of people universally who cannot accept DBD, DBCD can be considered a cultural and medical milestone that overcomes donation barriers.


Accurate alignment of toric intraocular lens (TIOL) to steep corneal astigmatic axis is important to achieve effective postoperative results. The authors compare the accuracy of astigmatism correction using automated and manual marking in TIOL implantation during cataract surgery.One hundred thirty-two eyes with nuclear density from Grade 2 to 4 were randomly subdivided into 2 groups . All patients underwent manual marking and the steep axis was compared to SensoMotoric Instruments (SMI). After phacoemulsification, 62 patients underwent toric IOL implantation using the SMI and 70 patients underwent toric IOL implantation using manual marking. Intraoperative measurement was the steep axis difference. Clinical measurements included preoperative and postoperative best corrected visual acuity (BCVA), and TIOL axis.P < 0.05).The intraoperative steep axis difference between SMI and manual marking was 7.86 ± 6.4 degrees. The difference between the preoperative steep axis and the postoperative TIOL axis using SMI (3.63 ± 1.12 degrees) was significantly lower than that using manual marking (8.29 ± 2.23 degrees) (The steep axis measurements may be different when using SMI vs. manual marking. The SMI is more accurate than manual marking for TIOL implantation during cataract surgery.ISRCTN12294725, Retrospectively registered, on 20 July 2018.Current Controlled Trials  With developments in cataract surgery, only correction of refractive errors with removal of the opaque lens and implantation of an intraocular lens is not the major goal of the cataract surgery. An estimated 35% of cataract patients have 1.00 diopter (D) or more than 1.00 diopter of preexisting corneal astigmatism .Limbal corneal relaxing incisions and implantation of a toric intraocular lens (IOL) have been used for correction of astigmatism in cataract patients , 4.Because 1° of off-axis rotation results in a loss of up to 3.3% of lens cylinder power , markingRecently, an eye tracking systems called SensoMotoric Instruments  has been used to visualize the steep corneal axis through the operating microscope during toric IOL implantation.To the best of our knowledge, there are no studies evaluating the efficacy of SMI in cataract surgery with toric IOL implantation.Here in, we compare the outcomes of toric IOL implantation marked with SMI and manual marking 2technique in the cataract patients with corneal astigmatism.This prospective randomized study comprised 132 eyes of 132 patients with cataract and coexisting corneal astigmatism more than 1.5 diopters (D) who were randomly assigned to undergo phacoemulsification and posterior chamber toric intraocular lens implantation at the Seoul St. Mary’s Hospital between February 2014 and December 2017. The study protocol followed the guidelines of the Declaration of Helsinki and the institutional review board of Bucheon St. Mary’s Hospital. Patients provided written informed consent after receiving an explanation of the surgical systems used in the study.One hundred thirty-two eyes were randomly divided into two groups . All patients underwent manual marking and the steep axis was compared to SMI intraoperatively. After phacoemulsification, 62 patients underwent toric IOL implantation using SMI (group 1) and 70 patients underwent toric IOL implantation using manual marking (group 2).Corneal pathology, pseudoexfoliation, history of ocular trauma and intraoperative complications such as posterior lens capsule rupture, lens dislocation, and ocular inflammation were excluded.Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), keratometer, refractometer, and corneal topography by a Scheimpflug imaging system  were assessed preoperatively.Intraoperative measurements included the steep axis difference between SMI and manual marking. The postoperative parameters measured at 1-day postoperatively, 1-month postoperatively, and 2-months postoperatively were uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), keratometer, refractometer, and corneal topography by a Scheimpflug imaging system (Pentacam). The visual acuity measurements had been recorded by masked personnel.For SMI marking, reference image of the steep axis was taken using a reference unit in the outpatient department. The reference image and data of the steep axis were transferred to the SMI system in the operating room.For manual marking, the axis-marking procedure was performed with topical anesthesia. The patient was seated at the surgical table and instructed to gaze at a distant target. Using a toric reference marker , the corneal limbus was marked at the 3-, 6-, and 9-o’clock positions. Next, with the patient lying on the surgical table, the steep axis was marked using a Mendez ring . The steep axis difference between SMI and manual marking was measured in all 132 eyes.Phacoemulsification was performed by the same surgeon (C.K.J.) using the Intrepid Infiniti system as described previous publication . After pP value of less than 0.05 was considered statistically significant.All data are expressed as the mean ± standard deviation. Pairwise comparisons of treatment group categorical variables were performed using the Mann-Whitney U test and continuous variables were analyzed using the unpaired t test. The analyses were performed using SPSS for Windows software . A P > 0.05).Table P < 0.05)  Fig. .Fig. 1InP < 0.05)  (Table P > 0.05)  was significantly lower than that using manual marking (8.29 ± 2.23 degrees) (P < 0.05). But, there was no significant difference in the BCVA between the two groups (P > 0.05)  in the SMI group was significantly higher than that in the manual marking group (5) Table .Microincision and small incision cataract surgery enables the almost astigmatically neutral phacoemulsification incisions . Newly dAstigmatic error has become the most important cause of low uncorrected visual acuity, as the phacoemulsification technique has improved. Astigmatism less than 0.5 D did not degrade visual acuity after cataract surgery . PatientBecause of the innovations in IOL technology and phacoemulsification technique, implantation of toric IOLs is the best method for correction of large corneal astigmatism more than 1.5 Diopters in patients requiring cataract surgery .Accurate alignment of toric IOL to steep corneal astigmatic axis is important to achieve effective postoperative results . InaccurMany methods are used to mark the steep corneal astigmatic axis. When the patient is sitting, the preoperative marking of the horizontal corneal meridian is the most important step . MarkingNowadays, digital image guidance such as SMI ensures accurate toric IOL alignment without manual marking during cataract surgery.P = 0.104) [P = 0.001) [P = 0.003) [Elhofi AH et al. compared the clinical outcome of digital and manual marking for toric intraocular lens (IOL) alignment . The mea= 0.104) . The mea= 0.001) . Also, t= 0.003) .However, there is no study comparing digital-marking and manual-marking in the same patients.P < 0.05)  between the two groups (05) Fig. .P < 0.05). The visual acuity (logMAR) in the SMI group was also significantly better than that in the manual marking group at the postoperative 2 months (P < 0.05).The accuracy of marking steep axis using SMI was significantly better than that using manual marking after 1 day Fig.  and 2 moAtchison DA et al. described that small levels of crossed cylinder blur produces losses in visual acuity that are dependent on the cylinder axis . The difP > 0.05).To the best of our knowledge, this is the first study comparing manual marking and SMI in the same patients during the operation. Our results showed that SMI causes a large difference in the steep astigmatic axis compared to manual marking. Also, the postoperative effectiveness of the toric IOL axis and uncorrected visual acuity for SMI were better than those for manual marking. However, there was no significant difference in TIOL rotation and best corrected visual acuity between the two groups (The only limitation of this study was that we provided the results obtained by a single surgeon. A multivariate evaluation should be performed in the future.Accurate marking of the steep astigmatic axis is important to achieve accurate alignment of the toric IOL and good postoperative uncorrected visual acuity. SMI would be a better instrument that provides accurate preoperative marking, intraoperative toric IOL alignment, and better postoperative results.


The differences between the two nisin containing diets were mainly attributable to differences in the nisin release from the starch matrices while the differences between the carriers were mainly attributable to the type of resistant starch they possessed. Indeed, the differences in the relative abundance of several genera in the mice consuming the starch dough and starch gel diets, in particular Akkermansia, the relative abundance of which was 0.5 and 11.9%, respectively , points to the potential value of resistance starch as a modulator of beneficial gut microbes. Intact nisin and nisin digestion products (in particular nisin fragment 22–31) were detected in the feces and the nisin was biologically active. However, despite a three-fold greater consumption of nisin in the group fed the nisin in starch dough diet, twice as much nisin was detected in the feces of the group which consumed the nisin in starch gel diet. In addition, the relative abundance of three times as many genera from the lower gastrointestinal tract (GIT) were significantly different  to the control for the group fed the nisin in starch gel diet, implying that the starch gel afforded a degree of protection from digestion to the nisin entrapped within it.There is a growing recognition of the role the gastrointestinal microbiota plays in health and disease. Ingested antimicrobial proteins and peptides have the potential to alter the gastrointestinal microbiota; particularly if protected from digestion. Nisin is an antimicrobial peptide that is used as a food preservative. This study examined the ability of nisin to affect the murine microbiota when fed to mice in two different starch based matrices; a starch dough comprising raw starch granules and a starch gel comprising starch that was gelatinized and retrograded. The effects of the two starch matrices by themselves on the microbiota were also examined. Following 16S rRNA compositional sequencing, beta diversity analysis highlighted a significant difference ( The gastrointestinal microbiota impacts on the health of the host in variety of ways, including through its potential to protect against infection, provide nutrients, and influence on bodyweight -based approach to examine the impact of nisin on the entire microbiota. Nisin has been consumed in vivo at up to 239 mg per kg body weight per day without any adverse effects on food consumption, body weight, hematology, ophthalmology, or gross pathology , the resistant starch content has been reported as 46% on a w/w basis  was obtained from Sigma Aldrich . Dextrose equivalent 12 maltodextrin (DE12 MD) was obtained from Roquette . All other reagents were from Sigma Aldrich  unless otherwise specified.The nisin A preparation used in this study was Nisaplin® . This preparation was concentrated by salting out as previously described  enriched nisin, 44% (w/w) HACS, and 55% (w/w) dilute HCl, with a final pH of 3. Starch gels without nisin were composed of 45% (w/w) HACS and 55% (w/w) dilute HCl, with a final pH of 3. The suspensions were split into 10 mL aliquots, heated at 115°C for 15 min and subsequently incubated at 4°C for a minimum of 16 h to ensure thorough retrogradation. Starch dough was prepared with and without nisin as follows. The starch dough balls with nisin comprised 1% (w/w) enriched nisin, 51.5% (w/w) HACS, 22.5% DE12 MD, and 25% (w/w) dilute HCl. The starch dough balls without nisin contained 52.5% (w/w) HACS, 22.5% DE12 MD, and 25% (w/w) dilute HCl. For the preparation of the nisin containing starch dough balls, the dilute HCL and enriched nisin (at pH 3) were heated at 115°C for 15 min and allowed cool to room temperature before addition to the rest of the ingredients, to ensure that the treatment of the nisin in the starch dough was comparable with that of the nisin in the starch gel. All the components of the starch dough balls were then mixed in a laminar flow cabinet. Each starch dough ball was thoroughly kneaded to achieve homogeneity and firmness. The starch dough balls were stored at 4°C until use.n = 10 per test diet).This study was carried out in accordance with European Directive 2010/63/EU. The protocol was approved by the University College Cork Animal Experimentation Ethics Committee (2011/005). Male C57BL/6JOlaHsd mice aged 3–4 weeks  were group housed (5 per cage) and were maintained in a 12:12 h light-dark cycle. During the initial 10 day acclimatization period, the mice were fed a standard nutritionally complete low-fat rodent diet ; this diet is henceforth referred to as the nutritionally complete (NC) diet. Subsequently weight matched mice were assigned to receive the following test diets: starch dough (SD), starch dough containing nisin (SD-N), starch gel (SG), and starch gel containing nisin (SG-N)  according to the manufacturer's instructions with some modifications. To increase DNA yield, after the addition of InhibitEX buffer, bead beating (3 min × 2) and an incubation at 95°C for 5 min, were performed. The samples were quantified using a Qubit® dsDNA High Sensitivity Assay Kit  in conjunction with a Qubit® 2.0 fluorometer . The initial amplification PCRs were performed as outlined in the Illumina 16S Metagenomic Sequencing Library Preparation Guide  with the following alterations; 30 amplification cycles were used and the amplification PCRs were each performed in a total volume of 60 μL which contained 25 ng DNA and 1 μL of each primer at a 10 μM concentration. The subsequent clean up using the AMPure® XP purification system  was scaled up appropriately to account for the greater volume. The index PCRs and subsequent AMPure® XP clean up were as outlined in the Illumina protocol. The samples were quantified using the Qubit® procedure and the concentrations normalized to 20 nM and pooled as per the Illumina protocol. The pooled sample (100 μL) was purified using AMPure® XP beads and the sample eluted using 50 μL of a 10 mM Tris solution. The pooled sample was quantified using the Qubit® procedure and sample quality was determined using an Agilent 2100 Bioanalyzer . The pooled sample was denatured and sequenced using a 500 cycle v2 kit on the MiSeq™ sequencing platform  following protocols outlined by Illumina at the Teagasc Sequencing Centre, Moorepark.Sequences were filtered on the basis of quality  and length  with PRINSEQ  and the samples were then restored to their original volumes using 0.1% TFA.To detect nisin in the fecal pellets, the nisin was extracted from the pellets as described by Rea et al.  with minRP-HPLC was carried out on a Jupiter, 5 μm, C18, 300 Å, 250 × 4.6 mm column from Phenomenex  with an acetonitrile  gradient as described previously  as previously described , the weight gain for the mice on the SG and SG-N diets from days 4 to 7 of the trial was significantly different  and the weight gain for the mice on the SD and SG diets from days 11 to 15 of the trial was significantly different . The total consumption per cage of the SD-N and SG-N test diets was 20.8 ± 2.5 and 6.5 ± 2.0 g, respectively, and the daily consumption of these diets were significantly different during the 6 h  and 8 h  consumption period. The total nisin consumption per cage over the course of the trial was 144 ± 14 and 52 ± 11 mg for the SD-N and SG-N diet groups, respectively, and the daily consumption of the nisin portion of those diets were also significantly different during the 6 h  and 8 h  consumption period. The average nisin consumption per day per cage during the 8 h consumption period was 17 ± 1 and 6 ± 2 mg for the SD-N and SG-N diets groups, respectively. Therefore, there was approximately a three-fold greater consumption of nisin by mice on the SD-N diet compared to mice on the SG-N diet. For SD-N compared to SD, SG-N compared to SG and SD compared to SG there were no statistically significant differences during the 6 h  and 8 h  consumption periods .The cumulative consumption of the NC and test diets and resultant body weight gain are shown in Figure The activity assays of the fecal pellets from mice consuming SD, SD-N, SG, and SG-N diets Figure  showed aMALDI TOF MS of the fecal pellets of mice on the SD-N Figure  and SG-NRP-HPLC of the fecal pellets of mice on the SG-N diet showed a single dominant peak Figure  that eluIntact nisin normally elutes from a RP-HPLC at 36% acetonitrile Figure  and subsp = 0.031, n = 3) nisin in the feces of the group fed SG-N (1.7 ± 0.2 ng/mg) compared to the groups fed SD-N (0.8 ± 0.1 ng/mg), despite the fact that less nisin was consumed by the group fed the SG-N diet, which would indicate that more intact nisin reached the lower GIT in SG-N-fed mice. Therefore, at the final time point (8 h test diet period), despite the significantly  greater nisin consumption of the mice on the SD-N diets, there was significantly  greater nisin in the feces from consumption of the SG-N diets.Quantifying the intact nisin in the feces at the final time point based on antibacterial activity showed significantly more .Following total metagenomic DNA extraction from the fecal pellets from day 15, 16S rRNA gene amplicons (V3–V4 region) were generated and sequenced using the Illumina MiSeq™ platform. The mean number of sequence reads and alpha diversity indices for each diet group are shown in Table Bacteroidetes and Firmicutes were the dominant phyla showing a relative abundance of 54–62 and 25–33%, respectively. There were no significant differences between the relative abundance of Bacteroidetes and Firmicutes across the diet groups  in the relative abundance between diet groups in the phyla Actinobacteria, Tenericutes, and Verrucomicrobia . These changes were reflected at the corresponding family level. However, there was also a significantly higher  relative abundance of the family Ruminococcaceae  in the proportions of the genera Anaerotruncus and Hydrogenoanaerobacterium, i.e., members of the Ruminococcaceae family, in mice that consumed the SG-N diet. Relative to the SD diet, the SD-N diet significantly  affected the relative abundance of only three genera; i.e., Lactobacillus and Bifidobacterium, which were lower, and Escherichia/Shigella, which were higher  greater in the mice fed the SD diet compared to the SG diet, whereas the relative abundance of the genera Akkermansia, Lachnospiracea incertae sedis, and Parabacteroides were all significantly  greater in the mice fed the SG diet relative to the SD diet  for the SG-N diet group compared to the SD-N diet group.There were also differences between the diet groups when compared on the basis of starch matrix. The relative abundance of the genera t Figure . In addits Table  and thisThe aim of this study was to determine if orally ingested nisin could be delivered to the lower GIT in two different starch matrices and subsequently impact on the lower GIT microbiota. Additionally, it was examined whether the type of starch itself could modulate the lower GIT microbiota.To the authors' knowledge Table  the onlyin vitro INFOGEST digestion model for the human GIT, detected nisin fragments corresponding to the N-terminus of nisin  post digestion, while no intact nisin was detected . In each case a single genus, i.e., Bifidobacterium, Anaeroplasma, and Akkermansia, respectively, comprised the majority (>98%) of the genera detected belonging to these phyla.More nisin was detected in the fecal samples of the mice on the SG-N diet despite them having consumed less nisin than those on the SD-N diet; implying that more intact nisin reached the lower GIT on the SG-N diet and that the starch gel may have afforded some protection to the nisin from digestion in the upper GIT. To the authors' knowledge there are no reported studies of the There were differences between the cumulative consumption of SD compared to SG Figure , howeverThere were also differences between the cumulative consumption of SG-N compared to SG, and SD-N compared to SD Figure , howeverp < 0.001, n = 10) in relative abundance, only two genera were also significantly different  in relative abundance when SD-N was compared to SD and SG-N was compared to SG. Additionally, of these two genera, Lachnospiraceae incertae sedis was only significantly different  in relative abundance in SG-N compared to SG, while Bifidobacterium showed significantly lower  relative abundance in both the SD-N compared to SD and SG-N compared to SG. It has been reported previously that Bifidobacterium are particularly sensitive to nisin relative to other intestinal bacteria  in relative abundance in SD-N compared to SD and SG-N compared to SG (Table Clostridium cluster XIVa), whereas the genera and family that significantly increased  in relative abundance in SD-N compared to SD and SG-N compared to SG (Table Escherichia/Shigella), contained Gram negative members (Ruminococcaceae) or may have had nisin resistant mechanisms that are known to be present in some strains (Lactococcus and Corynebacterium)  different in both the SD-N and SG-N diet groups compared to the SD and SG diet groups. Bifidobacteria have been demonstrated to attenuate Escherichia/Shigella in several studies, including in mice  is 1 mg nisin per kg body weight per day  when compared on the basis of resistant starch type including Akkermansia, Anaeroplasma, Bifidobacterium, Lachnospiracea, Odoribacter, and Parabacteroides have positive health associations  greater in mice fed the SG (RS3) than the SD (RS2) diet . This may be attributable to the type of starch, however confirmation of this would require further investigation using NC diets incorporating the various starch types.Resistant starch is capable of modulating the microbiota in the lower GIT and its effect depends on the type of resistant starch  favoring the abundance of different bacterial taxa. It was particularly notable how the relative abundance of the probiotic RG, AB, SM, CH, RR, PC, KN, and MR contributed to the design of the experiments. RG, PO, FC, and KN performed the experiments. RG performed statistical analysis of the data. RC performed the bioinformatic analysis of the data. RG, RC, PO, CH, RR, KN, and MR contributed to the interpretation of the data. RG wrote the manuscript. RC, PO, FC, AB, SM, CH, RR, PC, KN, and MR revised the manuscript. All authors approved of the final manuscript being submitted and agree to be accountable for the work detailed in the submitted manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GG and handling Editor declared their shared affiliation.