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To present common technical and non-technical issues leading to medicolegal litigation, illustrated by a series of 54 cases, with the aim of using these examples to prevent harm to patients and to prevent surgeons from having to experience the stress of litigation.A series of 78 medicolegal litigation cases reviewed by a single expert witness over 13 years from 2008 to 2021 was analysed by two reviewers. Twenty-nine cases were identified as having a non-technical learning point and 25 were identified as having a technical learning point. These are discussed using illustrative examples and the steps that could have avoided these issues are considered.All major issues and themes are illustrated with cases demonstrating the errors that lead to litigation and the often-simple steps that can be taken to avoid them. Out of 29 non-technical issues, 13 involved consent issues (45%), eight involved delays in treatment (28%) and eight involved failure to provide adequate safeguarding advice (28%). Out of 25 technical issues, 13 cases involved intra-operative problems (52%) including nine ureteric injuries, eight involved errors or omissions in the immediate preoperative period (32%) and four resulted from decisions around emergency decompression of the obstructed infected kidney. These emergency cases featured complications of amputation (two out of four) and death (one out of four). These decisions are complex and there are many subtleties to these cases, which are discussed in detail.We hope that this case series highlights the potentially catastrophic outcomes of even small errors of judgement, and allows careful stone surgeons to learn from the experiences of those unfortunate others without having to encounter these situations themselves.

Background: Ischemic heart disease following the obstruction of coronary vessels leads to the death of cardiac tissue and the formation of a fibrotic scar. In contrast to adult mammals, zebrafish can regenerate their heart after injury, enabling the study of the underlying mechanisms. One of the earliest responses following cardiac injury in adult zebrafish is coronary revascularization. Defects in this process lead to impaired cardiomyocyte repopulation and scarring. Hence, identifying and investigating factors that promote coronary revascularization holds great therapeutic potential. Methods: We used wholemount imaging, immunohistochemistry and histology to assess various aspects of zebrafish cardiac regeneration. Deep transcriptomic analysis allowed us to identify targets and potential effectors of Vegfc (vascular endothelial growth factor C) signaling. We used newly generated loss- and gain-of-function genetic tools to investigate the role of Emilin2a (elastin microfibril interfacer 2a) and Cxcl8a (chemokine (C-X-C) motif ligand 8a)-Cxcr1 (chemokine (C-X-C) motif receptor 1) signaling in cardiac regeneration. Results: We first show that regenerating coronary endothelial cells upregulate vegfc upon cardiac injury in adult zebrafish and that Vegfc signaling is required for their proliferation during regeneration. Notably, blocking Vegfc signaling also significantly reduces cardiomyocyte dedifferentiation and proliferation. Using transcriptomic analyses, we identified emilin2a as a target of Vegfc signaling and found that manipulation of emilin2a expression can modulate coronary revascularization as well as cardiomyocyte proliferation. Mechanistically, Emilin2a induces the expression of the chemokine gene cxcl8a in epicardium-derived cells, while cxcr1 , the Cxcl8a receptor gene, is expressed in coronary endothelial cells. We further show that Cxcl8a-Cxcr1 signaling is also required for coronary endothelial cell proliferation during cardiac regeneration. Conclusions: These data show that after cardiac injury, coronary endothelial cells upregulate vegfc to promote coronary network reestablishment and cardiac regeneration. Mechanistically, Vegfc signaling upregulates epicardial emilin2a and cxcl8a expression to promote cardiac regeneration. These studies aid in understanding the mechanisms underlying coronary revascularization in zebrafish, with potential therapeutic implications to enhance revascularization and regeneration in injured human hearts.

We present preliminary stone ablation rate results from an automated bench model using two pulse-modulated Ho:YAG lasers and a thulium fibre laser (TFL) in contact and non-contact modes. Ablation rate was assessed using automated apparatus that moved the laser fibre across flat BegoStone phantoms at a constant stone-to-fibre working distance (WD). Pre-soaked and unsoaked stones were used. A range of powers (20–60 W) was tested at WD of up to 3 mm. In pseudocontact, the prototype Ho:YAG laser produced higher ablation than the reference Ho:YAG laser at all powers tested (p p p

Introduction Incidental identification of small, asymptomatic renal calculi has risen with increasing high-resolution imaging. The natural history of such stones and small residual fragments remains unclear, however kidney stone disease (KSD) demands growing healthcare resource utilisation with wide-ranging costs of treatment and varying management recommendations. Materials and methods We systematically reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and PRISMA methodology. We searched Medline, Scopus, Embase, EBSCO, Cochrane library and Clinicaltrials.gov using themes of "asymptomatic", "nephrolithiasis", "observation", "symptoms", "admission", "intervention" and similar allied terms for all English language articles from 1996-2020 (25 years). Inclusion criteria were studies of minimum 50 patients, stones ≤10mm, and mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission and intervention. Results Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0-59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones 5mm, nor those 10mm. Risk of admission varied from 14-19% and risk of intervention from 12-35%. Meta-analysis demonstrated significantly decreased likelihood of intervention for stones 5mm and 10mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2 =0%, Cochran's Q=3.09, P=0.69; Intervention: I2 =0%, Cochran's Q=1.76, P=0.88). Conclusions This systematic review indicates that stone size is not a reliable predictor of symptoms, however risk of intervention is greater for stones 5mm and 10mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines.

Receptor interacting protein kinase 3 (RIPK3) can activate and be activated by ER stress. Islet inflammation associated with underlying activation of RIPK3 is conserved from zebrafish to humans. However, the role of RIPK3 in mammalian beta cells and the mechanism by which ER stress activates RIPK3 are not well defined. To investigate the role of RIPK3 in beta cell function, we generated beta cell specific Ripk3 knockout mice (Ripk3ßKO) in C57BL/6J background with or without the Akita mutation (Ins2C96Y/+, which causes ER stress induced beta cell apoptosis and early onset diabetes) (Ripk3ßKOAkita) . We found that the glucose tolerance was worsened in Ripk3ßKO mice than wildtype controls after 16 weeks of high fat diet. Similarly, Ripk3ßKOAkita mice had higher random blood glucose, lower circulating insulin, and worse glucose tolerance than Akita C57BL/6J mice as early as 4 weeks of age. Unexpectedly, isolated islets from Ripk3ßKO and Ripk3ßKOAkita mice have comparable glucose stimulated insulin secretion (GSIS) and are more resilient to palmitate-induced lipotoxicity than their control counterparts. Similarly, pharmacological inhibition of RIPK3 protected human islets from palmitate-induced impairment of GSIS ex vivo. We are currently investigating the role of specific islet inflammation stages in the divergent GSIS phenotypes between in vivo and ex vivo. To investigate how ER stress activates RIPK3 in beta cells, we tested the effect of inhibiting classic UPR branches on RIPK3 activation in MIN6 cells, a mouse beta cell line. We found that IRE1a activation appears to play an essential role in RIPK3 activation. Interestingly, Ripk3 knockdown in MIN6 cells also decreased IRE1a levels. We next seek to define the mechanism underlying the crosstalk between RIPK3 and IRE1a signaling pathways. Disclosure L.Yang: None. B.Yang: None. X.Tong: None. C.Dai: None. Z.Tang: None. W.Chen: None. Funding National Institutes of Health (DK117147)

Shunt active power filter (APF), with higher switching frequency, has a potential market for suppressing wideband harmonics in the more electric aircraft (MEA) or high-speed train (HST) power grid. In this case, the selective extraction of harmonic current reference is essential. Recursive discrete Fourier transform (RDFT) is widely adopted for its excellent selectivity and low computational burden. However, RDFT is tough to implement in the higher frequency APF with the shorter switching cycle, and suffers from the demerit of slow dynamics. To alleviate those, three improved RDFTs are proposed in this paper. Firstly, it is revealed that RDFT can be regarded as a series of DFT and inverse-DFT (IFT), and its settling time depends on the comb filter of DFT. Then, by rearranging the sampling frequency of DFT according to the extracted harmonic, the computational burden of twice-sampling RDFT (TS-RDFT) is reduced while satisfying the same extraction accuracy. Furtherly, to improve the dynamics of TS-RDFT while retaining the merits of simplicity and selectivity, the comb filter is reconfigured based on the load current spectrum. For balanced loads, the settling time of TS-RDFT can be shortened from 1 to 1/6 fundamental cycle in the synchronous reference frame. For unbalanced loads, it is shortened to 1/2 cycle in the $\alpha \beta $ frame. Finally, the simulations with Matlab for harmonic extraction in 400Hz grid and the experiments with the APF prototype for harmonic suppression in 50Hz grid are carried out to verify the effectiveness of the proposed methods.

In the flexible AC/DC distribution system supplying passive network, when the modular multi-level converter (MMC) inverter AC line fault occurs, the MMC short-circuit current amplitude is greatly affected by the control strategy, which may affect the operation performance of three-stage current protection. In view of this, a flexible AC/DC distribution network system supplying power to the passive network is built on the RTDS platform, and then the AC fault traverse strategy is designed in the MMC controller. Based on the thinking of coordinated control and protection of the fault through the strategy into two cases with no input to higher current protections performance simulation contrast, the simulation results show that asymmetric fault occurred when MMC inverter AC line, under the effect of communication failure through the strategy, the current main protection I, II period of refusing action, only by this line nearly backup protection current section III delay removal of fault. The three-stage current protection based on the fault current characteristics of pure AC system has poor action performance and is no longer suitable for the AC line of MMC inverter station.

INTRODUCTION AND OBJECTIVE:Holmium:YAG laser has been the lithotrite of choice for around 30 years in kidney stone surgery. The relatively high absorption in water is clinically useful but also lim...

Glucagon has emerged as the main regulator of extracellular amino acid homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other amino acid sensors in the α cell proliferation has not been described. Here, using gcgr-deficient zebrafish and cultured mouse islets, we show that α cell proliferation requires the calcium sensing receptor (CaSR) and downstream extracellular signalregulated protein kinase (ERK1/2). Inactivation of casr dampened α cell proliferation, which can be rescued by re-expression of CaSR or activation of the downstream Gq, but not Gi, signaling in α cells. CaSR was also unexpectedly necessary for mTORC1 activation in α cells. Furthermore, co-activation of Gq and mTORC1 induced α cell proliferation independent of hyperaminoacidemia. These results reveal another amino acid sensitive mediator, and identify major pathways necessary and sufficient for hyperaminoacidemia-induced α cell proliferation.

The shunt power capacitor will cause parallel resonance in the medium voltage (MV) power distribution system with nonlinear load. MMC-SAPF with low switching frequency is applied to handle this problem. Firstly, topology and control of device including modulation strategy is studied. Then, the parallel resonance mechanism in the MV power distribution system is analyzed. And then harmonic mitigation and resonance damping of MMC-SAPF is investigated. Finally, a large number of experimental results are tested to prove the utility of control strategy.

We assessed the literature around post-treatment asymptomatic residual stone fragments and performed a meta-analysis. The main outcomes were intervention rate and disease progression.We searched Ovid®, MEDLINE®, Embase™, the Cochrane Library and ClinicalTrials.gov using search terms: "asymptomatic", "nephrolithiasis", "ESWL", "PCNL", "URS" and "intervention." Inclusion criteria were all studies with residual renal fragments following treatment (shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy). Analysis was performed using 'metafor' in R and bias determined using Newcastle-Ottawa scale.From 273 articles, 18 papers (2,096 patients) had details of intervention rate for residual fragments. Aggregate intervention rates for ≤4 mm fragments rose from 19% (20 months) to 22% (50 months), while4 mm fragments rose from 22% to 47%. Aggregate disease progression rates for ≤4 mm rose from 25% to 47% and4 mm rose from 26% to 88%. However, there was substantial difference in definition of "disease progression." Meta-analysis comparing4 mm against ≤4 mm fragments: intervention rate for4 mm (vs ≤4 mm): OR=1.50 (95% CI 0.70-2.30), p0.001, ILarger post-treatment residual fragments are significantly more likely to require further intervention especially in the long term. Smaller fragments, although less likely to require further intervention, still carry that risk. Notably, there is no significant difference in disease progression between fragment sizes. Patients with residual fragments should be appropriately counselled and informed decision-making regarding further management should be done.

Holmium:YAG laser has been the lithotrite of choice for around 30 years in kidney stone surgery. Lasers have evolved over the years to offer higher power, increased pulse frequencies and longer pulse durations. The drivers for change have been to improve stone ablation and to minimise retropulsion. We report on a new prototype Holmium laser that fires multiple “micro-pulses” in “pulse packets” and discuss the stone phantom ablation rate results utilizing a bench model. The prototype laser demonstrated impressive stone ablation rates in our bench testing across a range of power settings. We will discuss the details of these results supporting that pulse-modulation with packets of micro-pulses are a promising technological development. (Disclaimers: Bench Test results may not necessarily be indicative of clinical performance. The testing was performed by or on behalf of BSC.

Stone retropulsion during laser lithotripsy results from various physical phenomena such as recoil momentum, bubble dynamics, and subsequent jet formation. Considerable stone retropulsion has been observed whereby the optical energy is converted into both mechanical and thermal energy as a distinctive bubble generation and collapse. It is hypothesized that by reducing the peak power and lengthening the pulse duration, we can reduce this conversion of optical energy into mechanical energy. This should maximize the thermal effects on the stone leading to enhanced ablation efficiency as well as less stone “chasing”. We are reporting on a new prototype Holmium laser with low pulse power and long temporal pulse durations in an attempt to minimize stone retropulsion.

This paper presents a 100 kHz switching frequency shunt active power filter (SAPF), which is based on SiC-MOSFET and DSP TMS320F28377D. Compared to the mostly about 10kHz switching frequency SAPF, 100kHz switching frequency makes it easy to design the current loop controller and achieve higher control bandwidth. By adopting the simple PI regulator to design the current loop, appropriate parameters of PI regulator and current loop bandwidth are given. Recursive discrete Fourier transform (RDFT) is used to extract harmonics selectively. By analyzing the relationship between different switching frequencies and harmonic extraction accuracy, harmonic suppression characteristics are improved at 100 kHz switching frequency. Meanwhile, due to the use of SiC-MOSFET, SAPF can operate stably with a low loss. A 10kVA prototype using CREE SiC power module CCS050M12CM2 is set up to verify the validity of the design method.

LCL filter is commonly adopted in grid-tied inverters to eliminate harmonics produced by the pulse width modulation (PWM), because of its superior attenuation ability. However, it introduces potential resonance that is especially critical when connected to a weak grid with grid impedance varying. Practically, the active damping methods are popular in stabilizing the inverter system due to their flexibility and power loss-less, compared to passive ones. Active methods are mostly implemented with additional digital filters, power converters, control loops or/and sensors, complicating inverter and increasing the costs. This paper provides an active damping method based on digital control delay (DCD) to ensure the stability of LCL-filtered inverters under the stiff or weak grid conditions. It is implemented with tuning the DCD to a proper region, which can be easily determined by method proposed in this paper. Finally, damping method is verified by simulation results in MATLAB/Simulink.

Islet inflammation is an important etiopathology of type 2 diabetes; however, the underlying mechanisms are not well defined. Using complementary experimental models, we discovered RIPK3-dependent IL1B induction in β cells as an instigator of islet inflammation. In cultured β cells, ER stress activated RIPK3, leading to NF-kB-mediated proinflammatory gene expression. In a zebrafish muscle insulin resistance model, overnutrition caused islet inflammation, β cell dysfunction, and loss in an ER stress-, ripk3-, and il1b-dependent manner. In mouse islets, high-fat diet triggered the IL1B expression in β cells before macrophage recruitment in vivo, and RIPK3 inhibition suppressed palmitate-induced β cell dysfunction and Il1b expression in vitro. Furthermore, in human islets grafted in hyperglycemic mice, a marked increase in ER stress, RIPK3, and NF-kB activation in β cells were accompanied with murine macrophage infiltration. Thus, RIPK3-mediated induction of proinflammatory mediators is a conserved, previously unrecognized β cell response to metabolic stress and a mediator of the ensuing islet inflammation.

The pathological feature of diabetes, hyperglycemia, is a result of an inadequate number and/or function of insulin producing β cells. Replenishing functional β cells is a strategy to cure the disease. Although β-cell regeneration occurs in animal models under certain conditions, human β cells are refractory to proliferation. A better understanding of both the positive and the negative regulatory mechanisms of β-cell regeneration in animal models is essential to develop novel strategies capable of inducing functional β cells in patients. Zebrafish are an attractive model system for studying β-cell regeneration due to the ease to which genetic and chemical-genetic approaches can be used as well as their high regenerative capacity. Here, we highlight the current state of β-cell regeneration studies in zebrafish with an emphasis on cell signaling mechanisms.

Affected by the control strategy of suppressing the negative sequence current and limiting the amplitude of the positive sequence current after the MMC fault, the fault characteristics of the converter side of the AC line interconnected with the MMC show that the negative sequence current is very small and the positive sequence current amplitude is different from the rated value Compared with the fault characteristics of the traditional power supply, there are obvious differences between the minor characteristics and the fault characteristics of the traditional power supply. And it has been simulated and verified on the RTDS simulation platform.

With the development of wind power technology, wind farms have gradually formed a mixed operation pattern dominated by DFIG and PMSG. By analyzing the short-circuit current characteristics when a fault occurred in the main transformer protection zone of the wind farm and the hybrid wind farm is connected to the grid, the possible impacts of the short-circuit current of the hybrid wind farm on the protection of the transformer is studied. The results show that after mixing different unit types, when the fault occurs in the main transformer protection zone of the wind farm, the short-circuit current contains the second harmonic component, and its attenuation speed is related to the number of PMSG, the number of DFIG, the fault location, and the severity of the fault. Under the influence of above factors, the blocking time of the second harmonic blocking protection will be prolonged, thereby increasing the operating time of the ratio differential protection.

The AC-DC hybrid distribution network based on modular multilevel converters (MMC) is beneficial for receiving distributed generation (DG), energy storage devices and DC loads. Therefore, the coordinated control of MMC and DG is very important for its safe operation. In this paper, doubly-fed induction generator (DFIG) are used as DG, and the control strategies of DFIG and MMC systems are analyzed. The system modeling research is carried out on a real time digital simulator (RTDS) platform. Then based on MMC control, an improved adaptive Crowbar circuit is proposed to improve inverter AC system low-voltage ride-through (LVRT) capability. The results show that the coordinated control strategy can better compensate the reactive power of the system to achieve LVRT, and verify the effectiveness of the control strategy adopted by the converter station.

The construction of Alternating Current and direct current (AC-DC) hybrid distribution networks is the future development trend. Due to the large number of distributed generation (DG) and power electronic devices, the fault characteristics on the AC side are more complicated. At the same time, due to the control strategy and topology, conventional protection methods has adaptability problems to the power system containing power electronics equipment. Therefore, it is of great significance to study the adaptability analysis of AC-DC hybrid distribution network protection to ensure the safe and reliable operation. This paper summarizes the research on the topological structure, fault characteristics, and protection principles, then analyzes the impact of AC-DC interactions on the protection configuration of the AC-DC hybrid distribution networks.

In winter, fish have suppressed immune functions and are susceptible to bacteria or virus which may lead to a high mortality. It is necessary to improve the immune response and disease resistance for overwintering fish. A recent study suggested that repeated handling increased the innate immune mechanisms and disease resistance in Senegalese sole. Therefore, the present study tested the hypothesis that appropriate repeated handling could compromise the immune depression and increase the disease resistance in channel catfish over winter. The experiment was carried out in field cages from Nov. 2012 to April 2013. Before the experiment, 35 fish with an average weight of 188.4 g were randomly assigned to one of six cages (2 mx2mx 2 m). Three cages were designed as the control group and did not receive any interfere. Fish in the other three cages received a weekly repeated handling of an air exposure for 5 min. Fish were not fed over winter. At the end of the trial, fish were challenged with Aeromonas hydrophila at a dose of 5.6 x 10(8) CFU ml(-1). The results showed that final body weight was not changed between groups. The spleen somatic index increased while the head kidney somatic index decreased in the unhandled fish after bacterial challenge, but these indices were not significantly changed in the repeated handled fish. Plasma cortisol levels in the control fish were induced at 6 h post challenge and then declined to the normal levels. However, plasma cortisol levels in the repeated handled fish did not show any significant change after bacteria challenge. The reduced inducement of heat shock protein 70 (HSP70) expression by repeated handling was observed in fish post bacterial challenge. After overwintering, repeated handled fish exhibited increased catalase (CAT) activities and reduced malondialdehyde (MDA) contents. Plasma total antioxidant capacity (TAOC), CAT and superoxide dismutase (SOD) activities of channel catfish were enhanced by repeated handling post bacterial challenge. The enhanced up-regulation of Interleukin 8 (IL8), IL1 beta-a, IL1 beta-b together with the immune related genes of Toll-like receptor 2 (TLR2), TLR3, nucleotide-binding oligomerization domain 1 (NOD1) and NOD2 by repeated handling was found in catfish after bacterial challenge. The present results indicated that a combination of signaling pathways through TLRs and NODs was involved in the innate immune response of the overwintering repeated handled channel catfish against invading bacteria. (c) 2015 Elsevier Ltd. All rights reserved.

High mortalities and suppressed immune functions of farmed fish over winter are the universal problems in aquaculture. It is necessary to improve the immune response and disease resistance in the overwintering fish. A recent study suggested that repeated handling increased innate immune mechanisms and disease resistance in Senegalese sole. Therefore, the present study evaluated the hypothesis that appropriate repeated handling could compromise the immune depression and increase the disease resistance in gibel carp over winter. The experiment was executed in field net cages (2 m × 2 m × 2 m) from Dec. 4, 2012 to Apr. 2, 2013. Three cages with 50 fish per cage were randomly designed as the control group and did not receive any interfere over winter. The other three cages received repeated handling with an air exposure for 5 min every week during the experiment. Fish were not fed over winter. At the end of the trial, fish were challenged with Aeromonas hydrophila at a dose of 1.5 × 10(8) CFU ml(-1). The results showed that no significant difference of final body weight was found between groups. The spleen and kidney somatic index increased in the control fish after bacterial challenge and showed a rising trend but not a statistical change in repeated handled fish. Plasma cortisol levels significantly increased in the control fish at 6 h post bacterial challenge and then declined. However, repeated handled fish did not show any significant change in plasma cortisol levels after challenge. The reduced inducement of heat shock protein 70 (HSP70) expressions by repeated handling was found in gibel carp post bacterial challenge. After overwintering, the repeated handled fish exhibited increased catalase (CAT) and superoxide dismutase (SOD) activities. Enhanced plasma CAT activities and reduced plasma malondialdehyde (MDA) contents were found in repeated handled fish over time against invading bacteria. Up-regulation of myeloid differentiation primary response gene 88 (MyD88) and interleukin 11 (IL11) was observed in repeated handled fish over time after bacterial challenge. The overexpression of IL11 was significantly reduced by repeated handling against invading bacteria compared to the control group. The present results implied that a MyD88-dependent signaling pathway was involved in the innate immune responses of gibel carp by repeated handling over winter against invading bacteria.

A modal parameter identification method of impulse response function, based on a modulated Gaussian wavelet transform, is presented. The factors influencing the identification accuracy and the required conditions of using this parameter identification method are discussed. Numerical verification of the proposed method is presented for several two-degree-of-freedom examples. A wind tunnel flutter experiment on a wing model of missiles is introduced. The data set from the flutter test is analyzed by using the proposed wavelet transform method. The first two order modal parameters of the wing model are identified, and then the critical dynamic stress is predicted by using the flutter stability parameter method. Finally, the results are compared with the results of FFT analysis.