Synapomorphies Research Articles

An in vitro analysis of the interaction between infliximab and granulocyte–monocyte apheresis

ObjectivePrimary non-response and secondary loss of response to anti-TNF agents are common in inflammatory bowel disease. Increasing drug concentrations are correlated to better clinical response and remission rates. Combination of granulocyte–monocyte apheresis (GMA) with anti-tumor necrosis factor (TNF) agents could be an option in these patients. The objective of our study was to perform an in vitro assay to determine if the GMA device can lead to infliximab (IFX) adsorption. Patients and methodsA blood sample was obtained from a healthy control. It was incubated with three concentrations of IFX (3, 6, and 9μg/ml) at room temperature for 10min. At that time, 1ml was collected to determine the IFX concentration. Then, 10ml of each drug concentration was incubated with 5ml of cellulose acetate (CA) beads from the GMA device at 200rpm for 1h at 37°C to simulate physiological human conditions. A second sample of each concentration was collected and IFX levels were determined. ResultsNo statistically significant differences were observed in the IFX levels in the blood samples before and after incubation with the CA beads (p=0.41) and after repeated measurements (p=0.31). Mean change was 3.8μg/ml. ConclusionsThe in vitro combination of GMA and IFX did not change the circulating levels of IFX at the three concentrations tested, suggesting that there is no interaction between the drug and the apheresis device in vitro and that they might be safely combined with each other.

Secondary flow and loss mechanisms of variable stator vanes in an annular cascade

Axial compressors with variable stator vanes require annular gaps and radial gaps from the endwalls for smooth adjustment, which induces complex secondary flows such as the penny leakage vortex and tip leakage vortex, leading to a negative impact on the aerodynamic performance. To better understand these mechanisms, numerical investigations were conducted on four different clearance configurations. The results show that the penny leakage vortex moves toward the suction side under the transverse pressure gradient and mixes with the hub corner stall vortex. This causes the corner separation to be further developed, leading to an increase in total pressure loss by 13.6%. However, the tip clearance leakage flow could reduce the transverse pressure gradient, which prevents penny leakage vortex from mixing with low-energy fluid in the corner region. Moreover, the hub corner stall vortex is also replaced by the tip leakage vortex, which effectively suppresses the range of corner separation. Under the comprehensive effects of the penny leakage vortex and the tip leakage vortex, the total pressure loss coefficient is increased only by 7.6%. Therefore, the mixing effect between the penny leakage vortex and low-energy fluid in the corner separation is the main reason for higher loss production of the cascade, and these findings provide theoretical support for the future application of flow control technology to reduce secondary flow loss.

365 Phase 2 trial in progress—lirentelimab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments

Abstract Atopic dermatitis (AD) is a chronic pruritic inflammatory dermatitis that affects approximately 16.5 million (7.3%) adults in the USA, of which around 6.6 million (40%) have moderate-to-severe disease. The current standard of care includes topical treatments supplemented with corticosteroids with and without immunosuppressants. Patients with AD inadequately controlled by topical treatments and immunosuppressants are often treated with biologics and/or JAK inhibitors. Some patients do not have an adequate clinical response or are unable to tolerate these treatments prompting the need for novel therapies. Mast cells (MCs) and eosinophils (eos) are implicated in the pathogenesis of AD. Sialic acid-binding Ig-like lectin (Siglec)-8 is expressed selectively on MCs and eos; engagement with an antibody results in broad inhibition of MC activation and eos depletion. Lirentelimab (AK002) is a humanized, nonfucosylated IgG1 monoclonal antibody that binds specifically to Siglec-8. Preclinical data demonstrate that lirentelimab can broadly inhibit multiple modes of MC stimulation that drive AD pathogenesis. Lirentelimab, administered every 4 weeks as an infusion (IV), has been tested in over 600 healthy volunteers and patients with inflammatory and allergic diseases; in those with concomitant AD, improvements in AD were observed. Overall, lirentelimab IV has been well-tolerated; the most common AE being infusion related reactions (IRRs) typically associated with the initial infusions. In a phase 1 study, a subcutaneous (SC) formulation of lirentelimab was well-tolerated with no IRRs. The results of these studies provide a strong rationale for conducting this phase 2 proof-of-concept, randomized, double-blind, placebo-controlled study of lirentelimab SC in adults with moderate-to-severe AD inadequately controlled by topical treatments (NCT05155085, ‘ATLAS’). Adults (18–80 years) are eligible for screening if they have had chronic AD presented for ≥3 years with moderate-to-severe symptoms defined as: Eczema Area and Severity Index (EASI) score ≥16, involvement of ≥10% of the Body Surface Area and Investigator Global Assessment (IGA) score ≥3, documented recent history of inadequate response to treatment with medications such as topical corticosteroids, calcineurin inhibitors, JAK inhibitors or PDE4 inhibitors (crisaborole), and biologic-naïve or biologic-exposed (secondary loss of response, intolerance or lack of access). The complete list of inclusion/exclusion criteria will be presented. One hundred and thirty patients will be randomized 1 : 1 to receive either seven SC injections of 300-mg lirentelimab or placebo every 2 weeks and then followed for 12 weeks after the last dose. The primary endpoint is the proportion of patients who achieve EASI-75 at week 14 (2 weeks after last dose) compared with baseline. All patients who receive study medication will be included in the safety analysis. Secondary endpoints include percent change in EASI at week 14 from baseline and proportion of patients with IGA of 0 or 1 and a 2-point improvement at week 14 compared with baseline. Patients who complete the study (Day 99 visit of double-blind period) will be given the option to enroll in an open-label extension for seven doses of 300-mg lirentelimab SC for 12 weeks. Qualified participants will receive medication, lab tests and medical care related to the study at no cost. This study is currently enrolling in the USA and Germany. Please visit clinicaltrials.gov (NCT05155085) or email atlas.info@allakos.com to learn more about this study.

Corrective osteotomy of the distal radius with palmar locking plate osteosynthesis without bone grafting and without cortical contact.

The aim of this study was to assess bone healing and secondary fracture displacement after corrective osteotomy of the distal radius without any cortical contact using palmar locking plates without bone grafting. Between 2009 and 2021, 11 palmar corrective osteotomies of extra-articular malunited distal radius fractures and palmar plate fixations without the use of bone grafts and without cortical contact, were assessed. All patients showed complete osseous restoration and significant improvement in all radiographic parameters. Except for one patient, there were no secondary dislocations or loss of reduction in the postoperative follow-up. Bone grafts may not be mandatory for bone healing and prevention of secondary fracture displacement after palmar corrective osteotomy without cortical contact and fixation with palmar locking plate.Level of evidence: IV.

The effects of the decline of a keystone plant species on a dune community plant-pollinator network

Ecological communities are maintained through species interactions, and the resilience of species interactions is critical to the persistence of natural communities. Keystone species play outsized roles in maintaining species interaction networks, and within plant-pollinator communities are high priorities for conservation. The loss of a keystone plant from a plant-pollinator network is expected to cause changes to network structure and composition of pollinator species, with the potential to cause secondary losses of plants and pollinators. To understand how the unmanipulated decline of a keystone plant affects the structure and composition of its network, we studied the plant-pollinator interactions of a Lake Michigan dune plant community where the population of the keystone plant, Cirsium pitcheri, is in rapid decline. The network prior to C. pitcheri decline (2016) was compared to the network as C. pitcheri continued to decline (2021 and 2022) in response to habitat loss. We find evidence that the loss of C. pitcheri altered network structure such that the community may be more sensitive to perturbations. Furthermore, changes in the composition of pollinators were explained by species turnover to a greater extent than by interaction rewiring, including the loss of bumblebees. Short-term negative consequences based on the changes to network structure and composition might lead to long-term effects on the persistence of the dune community. Our study exemplifies that the decline of a keystone plant can have negative implications for conservation of a plant-pollinator community. Using an interaction network framework to assess plant-pollinator communities has potential to develop strategies for best conservation and restoration practices in habitats vulnerable to habitat loss and disturbance.

Numerical and experimental investigation of quantitative relationship between secondary flow intensity and inviscid blade force in axial compressors

The secondary flow attracts wide concerns in the aeroengine compressors since it has become one of the major loss sources in modern high-performance compressors. But the research about the quantitative relationship between secondary flow and inviscid blade force needs to be more detailed. In this paper, a database of 889 three-dimensional linear cascades was built. An indicator, called Secondary Flow Intensity (SFI), was used to express the loss caused by secondary flow. The quantitative relationship between the SFI and inviscid blade force deterioration was researched. Blade oil flow and Computation Fluid Dynamics (CFD) results of some cascades were also used to cross-validate. Results suggested that all numerical cascade cases can be divided into 3 clusters by the SFI, which are called Clusters A, B and C in the order of the increasing SFI indicator. The corner stall, known as the strong corner separation, only happens when the SFI is high. Both calculations and oil flow experiments show that the SFI would stay at a low level if the vortex core at the endwall surface does not appear. The strong interaction of Kutta condition and endwall cross-flow is considered the dominant mechanism of higher secondary flow losses, rather than the secondary flow penetration depth on the suction surface. In conclusion, the inviscid blade force spanwise deterioration is strongly related to the SFI. The correlation of the SFI and spanwise inviscid blade force deterioration is given in this paper. The correlation could provide a quantitative reference for estimating secondary flow losses in the design.

Comparative Study of the Performance Improvement of an Axial Compressor with a Micro-Vortex Generator and a Suction Slot

Flow control methods have been gradually applied to improve the flow field characteristics of axial compressors. However, most of the current research is focused on the cascade, and few studies have taken a compressor as the research object. Therefore, a 3.5-stage transonic axial compressor is adopted to explore the characteristics of different flow control schemes. The effects of the micro-vortex generator (MVG), segmented boundary layer suction (BLS), and combined technology (COM) on the MVG and BLS are compared by the numerical simulation method. The research results are summarized as follows. The excessive accumulated low-energy fluid in the blade passage induces the occurrence of a corner stall in the last stage stator of an axial compressor. At this time, the compressor can still work, but the performance has accelerated deterioration. The flow characteristics are effectively improved when the MVG is introduced, the stall margin improvement ΔSM and the peak efficiency improvement Δηe of the last stage are 2.1% and 1.02%, respectively. Moreover, the BLS shows advantages in removing the three-dimensional reverse flow and decreasing the total pressure loss compared with the MVG, the ΔSM of the last stage is 2.69%, and the Δηe is 1.83%. When the combined technology is applied, it shows a significant advantage in delaying the occurrence of a corner stall, and the stall margin of the last stage is improved by 2.71%. Based on a quantitative analysis method using loss sources, the three flow control schemes show significant advantages in reducing the secondary flow loss sources and the wake loss sources. Above all, the BLS shows significant advantages in reducing the total pressure loss, and the COM shows an advantage in expanding the stable operating range. The research results will provide a reference for studies of flow control methods related to reducing flow losses and widening stability margins.

The Storyteller by Brandon Hobson

Reviewed by: The Storyteller by Brandon Hobson April Spisak Hobson, Brandon The Storyteller. Scholastic, 2023 [224p] Trade ed. ISBN 9781338797268 $17.99 Paper ed. ISBN 9781338893281 $7.99 Reviewed from digital galleys R Gr. 5-7 Despite his sister’s insistence that any evidence regarding their mother’s disappearance would either have been found or is long gone, Ziggy is certain there might be clues left in the desert caves Mom often explored, even after ten years. He decides to consult his classmate Alice, one of the few other Cherokee kids at their school, whose knowledge of trickster spirits, Nunnehi, convinces him the spirits might have some answers. Tamping down his usually overwhelming anxiety, Ziggy sets out on an epic night of adventure and revelations on a quest that is filled with talking animals (for example, an armadillo who asserts that he is Andrew Jackson, justifying genocide while quoting from a State of the Union speech) and mysterious figures who convey equally opaque messages. Ziggy is a carefully developed protagonist, and Hobson deftly explores the particular grief of mourning a missing person whose fate is unknown. Ziggy and his older sister hurt from the loss of their mother but also from their father’s inability to openly share stories about her because of his own pain, a secondary loss for Ziggy. The blending of the familiar and the fantastical works beautifully within the context of one long, exhausting, and anxiety-fueled night where Ziggy is doggedly determined to find some kind of peace or insight even if he cannot find his mom. Hobson seamlessly integrates Cherokee lore, history, and cultural details, grounding Ziggy in a loving family and community; a grim larger text about Ziggy’s mother being one of thousands of Native women to have vanished is also woven in. Mostly, however, the novel zooms in on sixth-grader Ziggy and his broadening understanding of his own potential to be more than his biggest fears. Avid readers will already likely believe fervently in the power of stories to engage, inform, and sometimes even heal, and Ziggy’s slow progression toward that knowledge is compelling and believable. [End Page 327] Copyright © 2023 The Board of Trustees of the University of Illinois

Implant Choice and Outcomes of the Sinus Tarsi Approach for Displaced Intra-articular Calcaneal Fractures.

Operative fixation of displaced intra-articular calcaneal fractures is considered the gold standard, for which multiple fixation methods are available. This study compares the (functional) outcome of screw fixation (SF), plate fixation (PF), and anatomical plate fixation (APF) via the sinus tarsi approach (STA). A total of 239 patients (265 fractured calcanei) who received surgical treatment of a displaced intra-articular calcaneal fracture via STA between 2011 and 2022 were included. Böhler angle (BA) measured immediately postoperatively (BA post-OR) and the decrease in BA at 1 year (∆BA) differed significantly in favor of PF/APF compared with SF (BA post-OR: SF vs PF P = .010 and SF vs APF P = .001; ∆BA: SF vs PF P = .032 and SF vs APF P = .042). Implant removal surgery was performed significantly less in the APF group as compared to the SF/PF groups (APF vs SF/PF; 9.9% vs 22.9%/23.7%, P = .015). Surgical site infections and secondary arthrodesis of the subtalar joint occurred equally in the 3 groups. Furthermore, the mean American Orthopaedic Foot & Ankle Society ankle-hindfoot scale, Foot Function Index score, and EuroQOL-5D-index / visual analog scale score, did not differ notably between SF, PF, and APF. The results show that both PF and APF are favored over SF because of an improved correction of BA measured directly postoperatively, a lower secondary loss of BA and, for APF, a lower implant removal rate. There was no difference in the rate of surgical site infections, need for secondary arthrodesis, nor functional outcome scores between different implants using the STA. Level III, retrospective cohort study.

Decrease in osteoporotic fracture in the western Kitakyushu region by the STOP-Fx study.

The Seamless Treatment of Osteoporosis against Fractures (STOP-Fx) study was initiated to provide and continue therapeutic interventions for registered patients with osteoporotic fractures. Women who visited six hospitals in the western Kitakyushu area for osteoporotic fractures between October 2016 and December 2018 were included in the study. Data collection for primary and secondary outcomes was conducted from October 2018 to December 2020, 2years after STOP-Fx study enrollment. The primary outcome included the number of surgeries for osteoporotic fractures after the STOP-Fx study intervention, while secondary outcomes were the intervention rate of osteoporosis treatment, incidence and timing of secondary fractures, and factors associated with secondary fractures and loss to follow-up. Concerning the primary outcome, the number of surgeries for osteoporotic fractures decreased since the STOP-Fx study initiation: 813 in 2017, 786 in 2018, 754 in 2019, 716 in 2020, and 683 in 2021. Regarding the secondary outcome, of the 805 patients enrolled, 445 were available for follow-up at 24months. Of the 279 patients who were untreated for osteoporosis at enrollment, 255 (91%) were on treatment at 24months. There were 28 secondary fractures, which were associated with increased tartrate-resistant acid phosphatase-5b and decreased lumbar spine bone mineral density during enrollment in the STOP-Fx study. As the demographics and medical area served by six hospitals in the western Kitakyushu region have not changed significantly since the STOP-Fx study initiation, the STOP-Fx study may have contributed in decreasing the number of osteoporotic fractures.

Estimating tissue-specific TNF mRNA levels prior to anti-TNFα treatment may support therapeutic optimisation in IBD patients

Background and aims Tumour necrosis factor-α (TNF) antagonists have improved the management of inflammatory bowel disease (IBD), however, their usage and administration persist to be suboptimal. Here, we examined the relationship between tissue-specific TNF mRNA expression in mucosal biopsies from IBD patients and anti-TNF treatment response. Methods Archived tissue samples from patients with luminal IBD that had all been or were in treatment with anti-TNF were included (18 adults and 24 paediatric patients). Patients were stratified into three groups according to anti-TNF response: responders, primary non-responders (PNR) and secondary loss of response (SLOR). TNF mRNA was detected using RNAscope in situ hybridisation (ISH) and the expression was quantified using image analysis. Results The ISH analysis showed varying occurrence of TNF mRNA positive cells located in lamina propria and often with increased density in lymphoid follicles (LF). Consequently, expression estimates were obtained in whole tissue areas with and without LF. Significantly higher TNF mRNA expression levels were measured in adults compared to paediatric patients in both the analyses with and without LF (p = .015 and p = .016, respectively). Considering the relation to response, the adult and paediatric patients were evaluated separately. In adults, the TNF expression estimates were higher in PNRs compared to responders with and without LF (p = .017 and p = .024, respectively). Conclusion Our data indicate that adult PNR have significantly higher TNF mRNA levels than responders. This suggests that higher anti-TNF dose may be considered for IBD patients with high TNF mRNA expression estimates from the start of treatment.

Two-Year Results of the Banded Versus Non-banded Re-sleeve Gastrectomy as a Secondary Weight Loss Procedure After the Failure of Primary Sleeve Gastrectomy: a Randomized Controlled Trial

BackgroundInsufficient weight loss or weight regain has been reported in up to 30% of patients after laparoscopic sleeve gastrectomy (LSG). Approximately 4.5% of patients who undergo LSG need revisional surgery for a dilated sleeve.MethodsThis randomized controlled trial compared the outcomes between banded (BLSG) and non-banded re-LSG (NBLSG) after weight regain. Percentage excess body weight loss (%EWL), percentage total weight loss (%TWL), associated medical problems, gastric volume measurement, and endoscopy were measured preoperatively and 1 and 2 years postoperatively.ResultsBoth groups (25 patients each) achieved similar % EWL and %TWL at six months, one year, and two years postoperatively (%EWL 46.9 vs. 43.6, 83.7 vs. 86.3, and 85.7 vs. 83.9) (p= > 0.151) (%TWL 23.9 vs. 21.8, 43.1 vs .43.3, 44.2 vs. 42.2) (p=>0.342), respectively. However, the body mass index was significantly lower with BLSG (24.9 vs. NBLSG, 26.9). Both groups showed a significant reduction in stomach volume after two years (BLSG -248.4 mL vs. NBLSG -215.8 mL). Food tolerance (FT) scores were significantly reduced in both groups, whereby BSLG had significantly lower FT with an average of -1.1 point. No significant differences were observed regarding improvement of the associated medical problems after the first and two years after revisional LSG or the postoperative complications between both groups.ConclusionLaparoscopic re-LSG is feasible and safe with satisfactory outcomes in patients with weight regain after LSG who have gastric dilatation without reflux esophagitis. Both groups had comparable significant weight loss effects and improvement of associated medical problems. The BLSG tends to have a more stable weight loss after two years with a significantly lower BMI, lower stomach volume, and less weight regain. Food tolerance decreased in both groups but reduced more in the BLSG group. After a 2-year follow-up, we may regard both procedures are safe, with no significant differences in the occurrence of complications and nutritional deficits.Graphical

Comparison of Secondary Flow Characteristics in Mixed-Flow Turbine between Nozzleless and Symmetric Nozzle Vane Angles under Steady-State Flow at Full Admission

In industrial applications, radial or mixed-flow turbines are frequently used in energy recovery systems, small turbines for producing power, and turbochargers. The implementation of radial or mixed-flow turbines helps to maintain high efficiency at a large range of pressure ratios by reducing the overall turbine losses and secondary flow losses. Numerous findings on secondary flow development research adopting double-entry turbines can be obtained in the public domain, except asymmetric volute, which is less well-researched. The focus of the present work is to investigate the evolution of secondary flows and their losses in a mixed-flow turbine used in an asymmetric volute turbine, by employing an experimentally validated three-dimensional computational fluid dynamics (CFD). The flow topology is analyzed to explain the formation and evolution of flow separations at the pressure, suction, and hub surfaces. As the opening angle of the nozzle vane increases, the incidence angle falls into the positive range while the maximum pressure difference between the shroud and hub decreases by about 40%. The results also show that the development of secondary flow accounts for the majority of losses and induced the centrifugal pressure head influence. The presence of symmetric nozzle vanes in both large and small scrolls is also found to have a significant detrimental effect on the turbine efficiency, which is 4% lower than the nozzleless case. Furthermore, significant flow separation is observed in the symmetrical nozzle vane configuration as opposed to that of nozzleless. In addition, the centrifugal pressure head indicated by the maximum pressure difference between the hub and shroud influences the overall turbine efficiency, as the symmetrical nozzle vane arrangement is introduced with two different turbine rotational speeds of 30 K rpm and 48 K rpm.

Response of terminal Schwann cells following volumetric muscle loss injury

An often-overlooked component of traumatic skeletal muscle injuries is the impact on the nervous system and resultant innervation of the affected muscles. Recent work in a rodent model of volumetric muscle loss (VML) injury demonstrated a progressive, secondary loss of neuromuscular junction (NMJ) innervation, supporting a role of NMJ dysregulation in chronic functional deficits. Terminal Schwann cells (tSCs) are known to be vital for the maintenance of NMJ structure and function, in addition to guiding repair and regeneration after injury. However, the tSC response to a traumatic muscle injury such as VML is not known. Thus, a study was conducted to investigate the effect of VML on tSC morphological characteristics and neurotrophic signaling proteins in adult male Lewis rats that underwent VML injury to the tibialis anterior muscle using a temporal design with outcome assessments at 3, 7, 14, 21, and 48 days post-injury. The following salient observations were made; first, although there is a loss of innervation over time, the number of tSCs per NMJ increases, significantly so at 48 days post-injury compared to control. The degree of NMJ fragmentation was positively correlated with tSC number after injury. Moreover, neurotrophic factors such as NRG1 and BDNF are elevated after injury through at least 48 days. These results were unanticipated and in contrast to neurodegenerative disease models, in which there is a reduction in tSC number that precedes denervation. However, we found that while there are more tSCs per NMJ after injury, they cover a significantly smaller percent of the post-synaptic endplate area compared to control. These findings support a sustained increase in neurotrophic activity and tSC number after VML, which is a maladaptive response occurring in parallel to other aspects of the VML injury, such as over-accumulation of collagen and aberrant inflammatory signaling.

Wolbachia springs eternal: symbiosis in Collembola is associated with host ecology.

Wolbachia are endosymbiotic alpha-proteobacteria infecting a wide range of arthropods and nematode hosts with diverse interactions, from reproductive parasites to obligate mutualists. Their taxonomy is defined by lineages called supergroups (labelled by letters of the alphabet), while their evolutionary history is complex, with multiple horizontal transfers and secondary losses. One of the least recently derived, supergroup E, infects springtails (Collembola), widely distributed hexapods, with sexual and/or parthenogenetic populations depending on species. To better characterize the diversity of Wolbachia infecting springtails, the presence of Wolbachia was screened in 58 species. Eleven (20%) species were found to be positive, with three Wolbachia genotypes identified for the first time in supergroup A. The novel genotypes infect springtails ecologically and biologically different from those infected by supergroup E. To root the Wolbachia phylogeny, rather than distant other Rickettsiales, supergroup L infecting plant-parasitic nematodes was used here. We hypothesize that the ancestor of Wolbachia was consumed by soil-dwelling nematodes, and was transferred horizontally via plants into aphids, which then infected edaphic arthropods (e.g. springtails and oribatid mites) before expanding into most clades of terrestrial arthropods and filarial nematodes.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens.

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Comparative effectiveness of bovine carotid artery xenograft and polytetrafluoroethylene in hemodialysis access revision.

When hemodialysis arteriovenous accesses fail, autogenous options are often limited. Non-autogenous conduit choices include bovine carotid artery xenografts (BCAG) and expanded polytetrafluoroethylene (PTFE), yet their comparative effectiveness in hemodialysis access revision remains largely unknown. A cohort study was performed from a prospectively collected institutional database from August 2010 to July 2021. All patients undergoing an arteriovenous access revision with either BCAG or PTFE were followed for up to 3 years from their index access revision. Revision was defined as graft placement to address a specific problem of an existing arteriovenous access while maintaining one or more of the key components of the original access (e.g. inflow, outflow, and cannulation zone). Outcomes were measured starting at the date of the index revision procedure. The primary outcome was loss of secondary patency at 3 years. Secondary outcomes included loss of post-intervention primary patency, rates of recurrent interventions, and 30-day complications. Pooled logistic regression was used to estimate inverse probability weighted marginal structural models for the time-to-event outcomes of interest. A total of 159 patients were included in the study, and 58% received access revision with BCAG. Common indications for revision included worn out cannulation zones (32%), thrombosis (18%), outflow augmentation (16%), and inflow augmentation (13%). Estimated risk of secondary patency loss at 3 years was lower in the BCAG group (8.6%, 3.9-15.1) compared to the PTFE group (24.8%, 12.4-38.7). Patients receiving BCAG experienced a 60% decreased relative risk of secondary patency loss at 3 years (risk ratio 0.40, 0.14-0.86). Recurrent interventions occurred at similar rates in the BCAG and PTFE groups, with 1.86 (1.31-2.43) and 1.60 (1.07-2.14) interventions at 1 year, respectively (hazard ratio 1.22, 0.74-1.96). Under the conditions of this contemporary cohort study, use of BCAG in upper extremity hemodialysis access revision decreased access abandonment when compared to PTFE.

Parasitic Component Small-Signal Modeling and Control of a Practical CLLC Resonant Converter

This article presents a comprehensive characterization of an asymmetric resonant CLLC dc/dc converter plant transfer function obtained using a generalized harmonic approximation (GHA)-based small-signal modeling approach. The effect of circuit parasitic components is comprehensively considered while deriving this model, and a quantified comparison of the resultant plant frequency response with a conventional first harmonic approximation (FHA)-based model is presented, which provides the designer insightful findings to design a robust and noise immune closed-loop compensator. Furthermore, a thorough explanation of a sliding mode control (SMC) along with detailed parameterization of the controller coefficients is provided by analyzing the system’s dynamic behavior and comparing the response with a conventional proportional–integral (PI)-based controller. In addition to the objective of designing a robust SMC controller, a phase shift-based secondary side modulation is introduced, which facilitates a significant reduction in the secondary side switching losses, thus enhancing the steady-state efficiency of the overall system. To validate and benchmark the open-loop plant response and controller dynamics, detailed steady-state results are elucidated for a 400–28- and 400–24-V voltage conversion at a rated load of 1 kW, with a resonant frequency of 500 kHz. Furthermore, a comprehensive experimental comparison between the proposed hybrid control scheme and the conventional PI controller is shown for two dynamic load changes corresponding to 10%–90% load step-up and 90%–10% load step-down. Quantification of dynamic response portrays a settling time reduction of 46.4% and an over/undershoot reduction of 33%, thus validating the robustness of the proposed control scheme.

EFFICIENCY OF DUAL THERAPY WITH VEDOLIZUMAB AND TOFACITINIB IN REFRACTORY ULCERATIVE COLITIS PATIENTS – SINGLE CENTRE EXPERIENCE

Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients.

Investigation of a centrifugal pump for energy loss due to clearance thickness while pumping different viscosity oils

The clearance between the stationary volute and rotating impeller of a centrifugal pump is crucial; however, it affects the internal flow and deteriorates the pump performance. This study performed a flow investigation through a numerical simulation to understand the effect of clearance and pumping fluid viscosity under the design and off-design conditions of a centrifugal pump. Numerical simulations were conducted by solving unsteady Reynolds-averaged Navier-Stokes (URANS) equations and validated using experimental results. Five three-dimensional centrifugal pump flow domains were created, by varying the clearance thickness, and simulated with three different fluid properties. Consequently, the numerical simulation results aided in understanding the internal flow pattern and estimating energy loss due to disk friction and leakage through the clearance. It was found that the disk friction and leakage losses, which cause secondary losses in the pump, were highly affected by the fluid properties and clearance thickness. The clearance thickness drastically affected both the volumetric and hydraulic efficiencies to leakage; however, beyond a particular value, it became less significant. Furthermore, the viscous oils caused a high disk friction loss; however, the leakage loss was less affected by the clearance thickness.