Increased Rejection Rates Research Articles

Advanced Modeling and Comparative Analysis of Nanofiltration Membrane Parameters: NF90 vs. NP010

Purpose: This study aimed to characterize commercial nanofiltration membranes (NF90 and NP010) by determining their membrane parameters and estimating osmotic pressure using the virial equation. Method: A comparison has been conducted using the Van't Hoff equation for both dilute and concentrated mixtures. Membrane parameters (σ, Ps, and ks) have been experimentally obtained, and osmotic pressure has been calculated using the virial equation, with results compared to the Van't Hoff equation. Various solutes, including lactose, Al3+, Mg2+, Na+, and Cl-, have been tested at different concentrations to investigate the membrane behavior. Result: Result: The virial equation has shown better agreement with experimentally measured fluxes than the Van't Hoff equation. With an increase in solute concentration, σ has decreased, while Ps and ks have increased. Higher cation valency has increased rejection rates, with lactose exhibiting the highest rejection. The rejection rates have followed the order of RLactose > RAl3+ > RMg2+ > RNa > RCl. The order of σ values has been as follows: σLactose > σAl3+ > σMg2+ > σNa+ > RσCl. While the order of Ps and ks values has been Cl->Na+>Mg2+>Al3+>lactose. Conclusion: The virial equation has proven to be more effective in estimating osmotic pressure. The findings have provided valuable insights into membrane behavior under varying conditions, optimizing the application of NF membranes across various industries.

Polyelectrolyte-modified covalent organic framework membranes for multivalent cation removal

Covalent organic framework (COF) has become a promising membrane material in chemical separations. However, the application of COF membranes for ion separation is still challenging, due to the mismatch between the pore size of COFs (1–5 nm) with the diameter of hydrated ions (<1 nm). Herein, a cationic polyelectrolyte surface modification strategy of COF membranes was proposed, by assembling a cationic polyelectrolyte (PEI, PDDA, PAH) layer on the surface of an anionic COF (TpPa-SO3H) membrane via dip coating. The cationic polyelectrolytes on the membrane surface offered abundant positive charges and reduced the surface pore size, leading to the synergistic enhancement of the size sieving and the electrostatic repulsion. Accordingly, effective rejection of multivalent cations was realized with a significantly increased rejection rate of 97.1 % for MgCl2, compared to that of TpPa-SO3H membrane (10.3 %). Furthermore, the polyelectrolyte-modified COF membrane exhibited desirable separation performance for heavy metal ions in water. The rejection rates for heavy metal salts, including CrCl3, CdCl2, CuCl2, PbCl2 and NiCl2, reached 98.5 %, 97.3 %, 97.0 %, 96.2 %, and 96.0 %, respectively, and remained above 95 % during the 7-day long-term operation test.

Splenectomy as a Risk Factor for Graft Rejection Following Endothelial Transplantation: Retrospective Study.

Anterior chamber-associated immune deviation (ACAID) is an active immunotolerance mechanism, which is induced by placing antigen into the anterior eye chamber as long as a major surgical trauma is avoided. For this reason, ACAID may be a major contributor to the favorable immunologic outcomes in Descemet membrane endothelial keratoplasty (DMEK). Rodent models have demonstrated the importance of a functional spleen for the development of an ACAID. This study aimed to investigate whether splenectomy leads to increased rejection rates after DMEK in humans. A retrospective evaluation was conducted on the course following DMEK at the Eye Center, Medical Center, University of Freiburg, for patients with a self-reported history of splenectomy compared to patients without this condition. Potential study patients were contacted by mail. A questionnaire to self-report splenectomy and the time thereof was sent out. The medical records of all consenting patients at the Eye Center were reviewed for graft survival and immune reactions. We asked 1818 patients after DMEK to report their history of splenectomy. A total of 1340 patients responded and were included in the study. Of these 1340 patients, 16 (1.2%) reported a history of splenectomy (ie, 26 DMEKs, with 10 patients being transplanted in both eyes and 6 patients being transplanted in 1 eye; median age at surgery 73.7, range 66.7-76.1 y). The remaining patients (1324 patients, ie, 1941 eyes) served as controls, with 1941 DMEKs (median age at surgery 71.5, range 64.1-77.2 y). Five (19%) out of the 26 eyes from the splenectomy group required a second transplant due to dislocation (n=2.8%), failure (n=2.8%), and rejection (n=1.4%). Kaplan-Meier analysis revealed no relevant difference compared with controls. Our results suggest that splenectomy has no major effect on the outcome following DMEK. Subsequent, ACAID may not be the main reason for the favorable immunological outcomes in DMEK, or the camero-splenic axis may be subordinate in humans. However, we only included 16 patients who underwent splenectomy, so it might be possible that we missed a minor effect.

Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant.

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.

Reduced floating-point precision in regional climate simulations: an ensemble-based statistical verification

Abstract. The use of single precision in floating-point representation has become increasingly common in operational weather prediction. Meanwhile, climate simulations are still typically run in double precision. The reasons for this are likely manifold and range from concerns about compliance and conservation laws to the unknown effect of single precision on slow processes or simply the less frequent opportunity and higher computational costs of validation. Using an ensemble-based statistical methodology, Zeman and Schär (2022) could detect differences between double- and single-precision simulations from the regional weather and climate model COSMO. However, these differences are minimal and often only detectable during the first few hours or days of the simulation. To evaluate whether these differences are relevant for regional climate simulations, we have conducted 10-year-long ensemble simulations over the European domain of the Coordinated Regional Climate Downscaling Experiment (EURO-CORDEX) in single and double precision with 100 ensemble members. By applying the statistical testing at a grid-cell level for 47 output variables every 12 or 24 h, we only detected a marginally increased rejection rate for the single-precision climate simulations compared to the double-precision reference based on the differences in distribution for all tested variables. This increase in the rejection rate is much smaller than that arising from minor variations of the horizontal diffusion coefficient in the model. Therefore, we deem it negligible as it is masked by model uncertainty. To our knowledge, this study represents the most comprehensive analysis so far on the effects of reduced precision in a climate simulation for a realistic setting, namely with a fully fledged regional climate model in a configuration that has already been used for climate change impact and adaptation studies. The ensemble-based verification of model output at a grid-cell level and high temporal resolution is very sensitive and suitable for verifying climate models. Furthermore, the verification methodology is model-agnostic, meaning it can be applied to any model. Our findings encourage exploiting the reduction of computational costs (∼30 % for COSMO) obtained from reduced precision for regional climate simulations.

Digital Nudging and Cookie Rejection: An Experiment

AbstractWhen browsing the Internet, web users tend to accept all cookies even though this may threaten their online security. We apply a salience nudge and a framing nudge to the design of a cookie banner and test their individual and combined effectiveness in fostering rejection of unnecessary cookies in an online experiment (N = 358). The salience nudge makes the rejection button more visible, and the framing nudge phrases button labels as negations. Compared to the control with no nudges, which elicited a rejection rate of 27%, the salience nudge increased rejection rate by 7 percentage points (but p = 0.305), the framing nudge by 18 pp (p = 0.009), and the combination of the two by 53 pp (p &lt; 0.0001). We also find that, when users are offered a customization option rather than the rejection button, only 3% of them select the option and reject non-necessary cookies. Finally, we explore how cookie rejection is related to the time users spend making the decision and to their personality traits. Our findings suggest that cookie rejection can indeed be fostered by an appropriate design of cookie banners and that legislation for protecting the online security of users should introduce specific design guidelines.

Why do manuscripts submitted to the Turkish Journal of Physical Medicine and Rehabilitation get rejected?

The study aimed to examine the reasons for the rejection of manuscripts, considering the increased rejection rates of our journal of up to 73% in 2022, and help authors realize what the editors and referees are paying attention to while assessing the manuscript. In this retrospective study, original articles, case reports, systematic reviews, and meta-analyses submitted and rejected to the Turkish Journal of Physical Medicine Rehabilitation were searched between January 1, 2016, and June 30, 2022. After reviewing the referee's evaluations and editorial opinions for all rejected articles, the reasons for rejection were classified under three main headings: journal, manuscript, and ethical issues. The manuscript issues were detailed under 11 subheadings. A total of 1,293 rejected submissions were reviewed. Of these, 35% were rejected at the editorial stage, while 65% were rejected after peer review. Thirty-three submissions were rejected for ethical reasons, 168 were out of the journal's field of interest, and 1,092 (84%) submissions were rejected for reasons related to the manuscript. The three most common reasons for rejection were protocol/methodology errors (44%), lack of contribution to the literature (41%), and lack of adequate discussion (40%). Before starting the studies, supporting the hypotheses with the current literature review, planning with the right protocol, and interpreting the findings in the discussion will facilitate the acceptance of the manuscripts to our journal.

Bayesian joint models for multi-regional clinical trials.

In recent years, multi-regional clinical trials (MRCTs) have increased in popularity in the pharmaceutical industry due to their ability to accelerate the global drug development process. To address potential challenges with MRCTs, the International Council for Harmonisation released the E17 guidance document which suggests the use of statistical methods that utilize information borrowing across regions if regional sample sizes are small. We develop an approach that allows for information borrowing via Bayesian model averaging in the context of a joint analysis of survival and longitudinal data from MRCTs. In this novel application of joint models to MRCTs, we use Laplace's method to integrate over subject-specific random effects and to approximate posterior distributions for region-specific treatment effects on the time-to-event outcome. Through simulation studies, we demonstrate that the joint modeling approach can result in an increased rejection rate when testing the global treatment effect compared with methods that analyze survival data alone. We then apply the proposed approach to data from a cardiovascular outcomes MRCT.

Ambient light exposure of photostimulable phosphor plates: is there a safe limit for acceptable image quality?

To subjectively assess radiographs obtained with photostimulable phosphor (PSP) plates exposed to clinical levels of ambient light prior to read-out to potentially set a safe limit for acceptable image quality. Six dental regions of a dry human skull were X-rayed using PSP plates from VistaScan and Express under four exposure times: 0.1, 0.2, 0.32, and 0.4 s. Before read-out, the PSP plates were exposed to ambient light for 0, 5, 10, 30, 60, and 90 s. Six observers were asked to classify the 288 resulting radiographs as acceptable or unacceptable based on the identification of anatomical structures and global image quality. The number of answers classifying radiographs as unacceptable was used to calculate a rejection rate; a pairwise comparison for better image quality was further conducted among radiographs considered acceptable. Reproducibility was tested by having 25% of all experimental groups reassessed. Intra- and interobserver agreement ranged from 0.87 to 1.00 and from 0.81 to 0.92, respectively. Exposure of PSP plates to ambient light increased rejection rates mostly as of 10 s. In the pairwise comparison, subtle differences were observed between radiographs obtained with PSP plates not exposed and those exposed to ambient light for 5 s. Ambient light exposure of PSP plates impairs the image quality of radiographs. A safe limit of ambient light exposure of 5 s for VistaScan and Express should be considered. Ambient light exposure of PSP plates within safe limits can avoid retakes and reduce unnecessary patient exposure to X-rays.

Methodology for the characterization and understanding of longitudinal wrinkling during calendering of lithium-ion and sodium-ion battery electrodes

The manufacturing of lithium-ion battery (LIB) cells is following a complex process chain in which the individual process steps influence the subsequent ones. Meanwhile, increasing requirements especially concerning the battery performance, sustainability and costs are forcing the development of innovative battery materials, production technologies and battery designs. The calendering process directly affects the volumetric energy density of an electrode and therefore of a battery cell. Calendering is still challenging as it causes high stresses in the electrode that lead to defects and thus increased rejection rates. The interaction between electrode material and process as well as the formation of defects is still not fully understood, especially when new material systems are used. In this context, the sodium-ion battery (SIB) is one post-lithium battery system that is a promising option to overcome the limitations of conventional LIBs. Therefore, this paper presents a first material and machine independent methodology to describe and understand the defect type longitudinal wrinkle, which mostly appears at the uncoated current collector edge of an electrode and in running direction. The aim is to systematically characterize the longitudinal wrinkles according to their geometry. The automatic data acquisition is carried out with a laser triangulation system and a 3D scanning system. The geometry values are calculated from the raw data and correlated to selected process parameters. The methodology is applicable regardless of the material as shown by exemplary results of NMC811 cathodes for LIB and hard carbon anodes for SIB. By using two different pilot calenders it is shown, that the data acquisition can be carried out independently of the machine. The presented methodology contributes to finding solutions for the avoidance of longitudinal wrinkling in any battery electrode and therefore to reducing the rejection rate.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients

IntroductionThe management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited.MethodsThis retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression.ResultsThere were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03–7.48), P = 0.044).ConclusionDespite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.

Investigating Defects of Esophageal Motility in Lung Transplant Recipients.

BackgroundLung transplant patients are at risk of developing chronic lung allograft dysfunction (CLAD) of which bronchitis obliterans syndrome (BOS) is the most common. These patients also are noted to develop gastrointestinal (GI) disease. Gastroesophageal reflux disease (GERD) is implicated in BOS, and diagnosis and treatment of GERD may help to decrease incidence of BOS.MethodsA total of 131 lung transplant recipients with post-transplant evaluation between 2012 and 2019 were studied. Of 60 post-transplant evaluations with at least 6 months of post-transplant follow-up that included impedance testing, high-resolution manometry (HRM), and pH testing, procedures were performed according to recognized standards.ResultsOf 60 patients, 56 (93%) were alive at 1-year post-transplant. The patients were found to have high rates of GI motility diseases: 37 patients (62%) had abnormal impedance testing, 50 patients (83%) had abnormal HRM results, 22 patients (37%) had abnormal pH test results. There was associated high rejection rates in patients with abnormal esophageal motility. There were 37 patients that had abnormal impedance test results and of those 25 patients (67%) developed rejection. Fifty patients had abnormal post-transplant HRM studies, 33 (66%) had an acute cellular rejection episode. Twenty-two patients had abnormal pH results, with 14 (63%) having an acute cellular rejection.ConclusionsPatients undergoing lung transplantation were found to have increased incidence of abnormal GI motility studies of the esophagus. These patients were further found to have increased rejection rates and BOS which has been associated with worsened mortality. Developing a formalized pre- and post-transplant motility study process, using evolving technologies for these patients, may provide guidance of at-risk patients for CLAD and early treatment to prevent CLAD.

De novo donor-specific HLA antibodies reduce graft survival rates and increase the risk of kidney transplant rejection: A single-center retrospective study

BackgroundWe investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients. MethodsThe sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys. ResultsDnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (<4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell–mediated rejection (p < 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p < 0.05). ConclusionDnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.

A chitosan/dopamine-TiO2 composite nanofiltration membrane for antifouling in water purification

A major obstacle for the development of the cellulose-based nanofiltration membrane is its fouling. In this study, a novel cellulose-based composite nanofiltration membrane (CS/DA-TiO2-NFM) with excellent anti-fouling performance was prepared through casting of both chitosan (CS) and TiO2 modified by dopamine (DA-TiO2) on the cellulose substrate membrane. DA-TiO2 was successfully introduced into the surface of membrane, resulting in significant improvement in its hydrophilicity due to the formation of dense CS layers. Furthermore, both CS and DA-TiO2 were effective antimicrobial agents (against E. coli 90.6% and S. aureus 95.1%) that could minimize the accumulation of bacteria on the CS/DA-TiO2-NFM. For the antifouling test against BSA, the irreversible recovery ratio of the CS/DA-TiO2-NFM was only 23.25% of the control (no CS/DA-TiO2 modified NFM). In addition, the CS/DA-TiO2-NFM exhibited an increased rejection rate of MgSO4 (enhanced 40.93%) and water-flux (enhanced 18.10%) compared with the control. These results highlight the potential of the presented approach for designing membranes with effective separation performance and antifouling for drinking water treatment.

Electrokinetic Enhancement of Water Flux and Ion Rejection through Graphene Oxide/Carbon Nanotube Membrane.

Graphene oxide (GO) is promising for constructing next-generation high-performance membranes for water treatment and desalination. However, GO-based membranes are still subjected to low ion rejection or limited water flux. Herein, the electrokinetic effect is employed as a new strategy for the coenhancement of water flux and ion rejection through an ethylenediamine-polystyrenesulfonate intercalated graphene oxide/carbon nanotube (GO&EDA-PSS/CNT) asymmetric membrane. Benefiting from the external voltage applied across the GO&EDA-PSS layer, the electrokinetically driven water transport velocity is significantly increased from 0 to 23.7 μm s-1 with increasing the voltage from 0 to 3.0 V. As a result, the water flux is improved from 9.1 to 17.4 L m-2 h-1 under a transmembrane pressure of 1 bar. Simultaneously, the rejection rate for NaCl is increased from 52.4% to 78.3%. Numerical analysis reveals that the increased rejection rate is attributed to the electrokinetic enhancements of water transport through the membrane and ion partitioning between the membrane and bulk solution. These results indicate that the assistance of the electrokinetic effect is an effective means to improve membrane filtration performance, which provides a new perspective on the design of advanced membranes for achieving high water flux and rejection efficiency.

Natural and artificial scents do not increase egg rejection rates of model brood parasitic eggs by American robins (Turdus migratorius)

Hosts of obligate avian brood parasites can diminish or eliminate the costs of parasitism by rejecting foreign eggs from the nests. A vast literature demonstrates that visual and/or tactile cues can be used to recognize and reject natural or model eggs from the nests of diverse host species. However, data on olfaction-based potential egg recognition cues are both sparse and equivocal: experimentally-applied, naturally-relevant (heterospecific, including parasitic) scents do not appear to increase egg rejection rates in two host species, whereas unnatural scents (human and tobacco scents) do so in one host species. Here I assessed the predictions that (i) human handling of mimetically-painted model eggs would increase rejection rates, and (ii) applying unnatural or natural scents to mimetically or non-mimetically painted model eggs alters these eggs’ respective rejection rates relative to controls. I studied wild American Robins (Turdus migratorius), a robust rejecter species of the eggs of obligate brood parasitic Brown-headed Cowbirds (Molothrus ater). There was no statistical evidence to support either prediction, whereas poorer color-mimicry was still a predicted cause of greater egg rejection in this data set. Nonetheless, future studies could focus on this and other host species and using these and different methods to apply and maintain the scenting of model eggs to more directly test hosts’ use of potential olfactory cues in the foreign-egg rejection process.

A cellulose-based nanofiltration membrane with a stable three-layer structure for the treatment of drinking water

Nanofiltration membrane (NFM) is an effective and advanced semi-permeable membrane (pore size: 1 ~ 2 nm) for deep purification of drinking water due to their low operating pressure and high divalent salt ion rejection. In this work, a stable cellulose-based polyamide nanofiltration membrane (NF-PDA-RCM) with a unique three-layered structure was prepared for advanced treatment of drinking water, via the method of chemical bond connection followed by the interfacial polymerization strategy. The regenerated cellulose membrane (RCM), as the supporting layer of NFM, prepared by phase inversion method has good physical compatibility and abundant porous channels. Further, the flux of NFM can be controlled by adjusting the pore size of the RCM. Through Michael addition reaction, the supporting layer and the active layer of NF-PDA-RCM are connected by the covalent bonds, resulting in a great improvement in the stability of NF-PDA-RCM. The resultant NF-PDA-RCM has increased rejection rate of MgSO4 (enhanced about 9.3%) and water-flux (enhanced about 78.5%) compared with that of no polydopamine (PDA) modified NFM. The RCM are completely biodegradable, allowing the NF-PDA-RCM to be a promising candidate for treating drinking water.

Review on measuring training effectiveness, an integrated model of training effectiveness and satisfaction with employee development interventions

The world is changing rapidly, and with businesses required to be more competitive, the need for employees to be on top of their job has increased. Change is the order of the day, working methods and techniques are witnessing a change giving birth to the need for employees to learn continuously. The most innovative form of technology used, regardless of company size was videotapes. The major barriers or obstacles to using more innovative tools (i.e., computer-based) were high costs and short life span of current computer technology. Every organization determines its training needs according to its own environment and observed signals. Performance reports, for example, may indicate that performance is declining (e.g., decrease in production numbers, lower quality, increased number of accidents, increased rejection rates, etc).

The Evolution of Animal Models in Wound Healing Research: 1993-2017.

Significance: Wound healing is a complex and dynamic series of events influenced by a variety of intrinsic and extrinsic factors. Problematic wounds, particularly chronic wounds and pathologic scars, remain clinically significant burdens. Modeling physiologic and aberrant wound repair processes using in vitro or in vivo models have contributed to Advances in Wound Care (AWC); however, the fidelity of each model used, particularly with respect to its species-specific limitations, must be taken into account for extrapolation to human patients. Twenty-five years of wound healing models published in Wound Repair and Regeneration (1993-2017) and AWC (2012-2017) were collected and analyzed to determine trends in species utilization and models used. Recent Advances: In 25 years, 1,521 original research articles utilizing one or more wound models were published (total of 1,665 models). Although 20 different species were used over the course of 25 years, 5 species were most commonly utilized: human, mouse, rat, pig, and rabbit. In vivo modeling was used most frequently, followed by in vitro, ex vivo, and in silico modeling of wound healing processes. Critical Issues: A comparison of articles from 1993 to 1997 and 2013 to 2017 periods showed notable differences in model and species usage. Experiments utilizing mouse and human models increased, while the usage of pig models remained constant, rabbit and rat models declined in the more recent time period examined compared to the time period two decades before. Future Directions: This analysis shows notable changes in types of models and species used over time which may be attributed to new knowledge, techniques, technology, and/or reagents. Explorations into mechanisms of limb regeneration and wound healing of noncutaneous tissues have also contributed to a shift in modeling over time. Changes within the journals (i.e., page expansion and increased rejection rates), research funding, and model expense may also influence the observed shifts.

Splenomegaly May Increase Rejection Rates in Matched-Related Transplants for Thalassemia, This Effect Is Mitigated by Additional Immunosuppression.

Background Severe thalassemia syndromes (ST) are highly curable by BMT but rejection may occur in 5 to 30% of cases. Splenomegaly was shown to increase the risk of rejection even in low risk transplant setting in our earlier review (https://ash.confex.com/ash/2017/webprogram/Paper104001.html). Objective To assess the impact of splenomegaly on rejection and study the effectiveness of increased immunosuppression in the preparative regimen. Methods We compared transplant outcomes in patients with splenomegaly between two conditioning regimens: Our earlier protocol (Regimen A) and a more recent modified one (Regimen B) (Fig 1). Our BMT network used Regimen A between August 2013 and Dec 2016 which comprised of busulfan (14 mg/kg oral, not adjusted to serum levels), cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (ATG) (Genzyme 4 mg/kg or Fresenius 16 mg/kg on days -12 to -10). Regimen B consisted of same backbone as Regimen A except Fludarabine total dose of 150 mg was added upfront and ATG dose was increased to 7 mg/kg in case of splenomegaly and or sex mismatched transplants (Jan 2017 to Jun 2108). G-CSF-primed bone marrow (5 μg/kg/dose twice daily for 3 to 5 days prior to harvest) was the source of hematopoietic stem cells in all cases. All patients were considered low risk based on liver size 3 by ultrasound measurement adjusted for height. All sibling couples were HLA-compatible. Results In total of 168 patients analyzed, 87 for Regimen A and 81 with Regimen B. Regimen A had 11 patients and Regimen B had 20 patients with significant splenomegaly. There was noticeable overall improvement in rejection rates between Regimen A and Regimen B patient groups (Fig 2) (p = 0.028) while improvement in rejection rates within the splenomegaly group between Regimen A and Regimen B was far more significant (Fig 3) (p = 0.0045). We could not detect any difference in variables potentially associated with rejection risk such as donor-recipient sex mismatch (p = 0.4), serum ferritin at BMT (p = 0.17), pre-BMT blood transfusions (p = 0.37), age at BMT (p = 0.59), ABO mismatch (p = 0.53) and spleen Z scores measured by ultrasound at BMT(p = 0.54) by univariate analysis. The median total nucleated cell dose was higher on Regimen B (9.45, IQR 7.065 – 11.815) compared to Regimen A (6.47, IQR 5.725 – 8.102) (p = 0.023) and the median follow up was shorter (median 15.8 vs 9.35 months) factors which may have contributed to improved results in Regimen B. Conclusion The increased risk of rejection related to splenomegaly can be decreased by adding fludarabine to the standard ATG- Bu-Cy protocol without significantly increasing transplant-related morbidity and mortality or resorting to splenectomy pre-BMT.