A theoretical modeling framework for motile and colonial harmful algae.

Climate change is leading to an increase in severity, frequency, and distribution of harmful algal blooms across the globe. For many harmful algae species in eutrophic lakes, the formation of such blooms is controlled by three factors: the lake hydrodynamics, the vertical motility of the algae organisms, and the ability of the organisms to form colonies. Here, using the common cyanobacterium Microcystis aeruginosa as an example, we develop a model that accounts for both vertical transport and colony dynamics. At the core of this treatment is a model for aggregation. For this, we used Smoluchowski dynamics containing parameters related to Brownian motion, turbulent shear, differential setting, and cell-to-cell adhesion. To arrive at a complete description of bloom formation, we place the Smoluchowski treatment as a reaction term in a set of one-dimensional advection-diffusion equations, which account for the vertical motion of the algal cells through molecular and turbulent diffusion and self-regulating buoyant motion. Results indicate that Smoluchowski aggregation qualitatively describes the colony dynamics of M. aeruginosa. Further, the model demonstrates wind-induced mixing is the dominant aggregation process, and the rate of aggregation is inversely proportional to algal concentration. Because blooms of Microcystis typically consist of large colonies, both of these findings have direct consequences to harmful algal bloom formation. While the theoretical framework outlined in this manuscript was derived for M. aeruginosa, both motility and colony formation are common among bloom-forming algae. As such, this coupling of vertical transport and colony dynamics is a useful step for improving forecasts of surface harmful algal blooms.

Anticholinergic burden of patients with dementia attending a Psychiatry of Later Life service.

OBJECTIVES: Older adults with dementia are particularly vulnerable to adverse outcomes resulting from anticholinergic use. We aimed to: (i) Examine the anticholinergic burden of patients with dementia attending a Psychiatry of Later Life (PLL) service (ii) Examine concomitant prescription of acetylcholinesterase inhibitors (AChEIs) and anticholinergics and (iii) Compare the Anticholinergic Cognitive Burden (ACB) scale with a recently published composite list of anticholinergics. METHODS: Retrospective chart review of new referrals with a diagnosis of dementia (n = 66) seen by the PLL service, Tallaght University Hospital, Dublin, Ireland, over a consecutive period of 4 months. RESULTS: The mean ACB score was 2.2 (range = 0-9, SD = 2.1). 37.9% (n = 25) had a clinically significant ACB score (>3) and 42.1% (n = 8) of those taking AChEIs had a clinically significant ACB score. A significantly greater number of medications with anticholinergic activity were identified using the composite list versus the traditional ACB scale (2.3 v.1.5, p = 0.001). CONCLUSIONS: We demonstrated a significant anticholinergic burden amongst patients with dementia attending a specialist PLL service. There was no difference in anticholinergic burden between groups prescribed and not prescribed AChEIs, indicating that these medications are being prescribed without discontinuation of potentially inappropriate medications with anticholinergic activity. The true anticholinergic burden experienced by patients may be underestimated by the use of the ACB score alone, although the clinical significance of this finding is unclear. Calculation of true clinical anticholinergic burden load and its translation to a specific rating scale remains a challenge.

The Impact of Body Mass Index Upon the Efficacy of Adalimumab in Hidradenitis Suppurativa.

Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. Individual patient data from 578 PIONEER Phase 3 participants were analyzed. Descriptive, multivariable regression analysis and receiver operating characteristic (ROC) curves were calculated to assess the relationship between BMI and clinical outcome measures using R v3.5.3. Participants in the overweight and obese BMI category had reduced odds (58 and 67%, respectively) of achieving HiSCR [OR = 0.42 (95%CI -0.19, 0.91) p = 0.03], [OR = 0.33 (95%CI 0.16, 0.67) p = 0.002] compared to participants with BMI < 25. Reduction in AN count and IHS4 score was not significantly associated. ROC analysis did not reveal any cut off value predictive of treatment outcome. No correlation between BMI and baseline disease activity or covariate interactions were identified. These findings suggest BMI is a significant covariate in the setting of lower baseline disease activity, supporting the concept of disease heterogeneity and differential therapeutic response to Adalimumab.

On generating functions in additive number theory, II: lower-order terms and applications to PDEs.

We obtain asymptotics for sums of the form ∑ n = 1 P e α k n k + α 1 n , involving lower order main terms. As an application, we show that for almost all α 2 ∈ [ 0 , 1 ) one has sup α 1 ∈ [ 0 , 1 ) | ∑ 1 ≤ n ≤ P e α 1 n 3 + n + α 2 n 3 | ≪ P 3 / 4 + ε , and that in a suitable sense this is best possible. This allows us to improve bounds for the fractal dimension of solutions to the Schrödinger and Airy equations.

Dermal tunnels influence time to clinical response and family history influences time to loss of clinical response in patients with hidradenitis suppurativa treated with adalimumab.

BACKGROUND: Clinical response in hidradenitis suppurativa (HS) is most commonly assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR) measure. Dermal tunnels, increased body mass index, smoking and antibiotic use significantly decrease the odds of achieving HiSCR. However, there are few data exploring if clinical features are also associated with length of time to achieve clinical response and/or time to lose clinical response. AIM: To explore whether variables associated with achievement of HiSCR are associated with time to achieve HiSCR and time to loss of HiSCR in patients with HS treated with adalimumab 40 mg weekly in the PIONEER open-label extension study. METHODS: Time-to-event analyses were performed to estimate time to achieve HiSCR and time to loss of HiSCR. The log rank test was used to compare cumulative incidence curves for a priori patient- and disease-associated factors. Cox regression analysis was performed to compare time-to-event outcomes in the presence of a priori variables. All statistical analyses were completed with R software (V3.5.3). RESULTS: Presence of dermal tunnels significantly increased the time to achieve HiSCR (median 32.6 vs. 14.3 weeks, P = 0.02) and the hazard ratio (HR) was significant after controlling for patient and disease factors (HR = 0.70, 95% CI 0.51-0.96, P = 0.03). A positive family history of HS significantly decreased the time to loss of HiSCR (median 11.4 vs. 18 weeks, P < 0.001) and remained significant in Cox regression analysis (HR = 2.01, 95% CI 1.40-2.88, P < 0.001). CONCLUSION: The presence of dermal tunnels significantly influences the odds of achieving HiSCR and the time to achieve HiSCR, while family history influences time to loss of HiSCR.

Chaos in a simple model of a delta network.

The flux partitioning in delta networks controls how deltas build land and generate stratigraphy. Here, we study flux-partitioning dynamics in a delta network using a simple numerical model consisting of two orders of bifurcations. Previous work on single bifurcations has shown periodic behavior arising due to the interplay between channel deepening and downstream deposition. We find that coupling between upstream and downstream bifurcations can lead to chaos; despite its simplicity, our model generates surprisingly complex aperiodic yet bounded dynamics. Our model exhibits sensitive dependence on initial conditions, the hallmark signature of chaos, implying long-term unpredictability of delta networks. However, estimates of the predictability horizon suggest substantial room for improvement in delta-network modeling before fundamental limits on predictability are encountered. We also observe periodic windows, implying that a change in forcing (e.g., due to climate change) could cause a delta to switch from predictable to unpredictable or vice versa. We test our model by using it to generate stratigraphy; converting the temporal Lyapunov exponent to vertical distance using the mean sedimentation rate, we observe qualitatively realistic patterns such as upwards fining and scale-dependent compensation statistics, consistent with ancient and experimental systems. We suggest that chaotic behavior may be common in geomorphic systems and that it implies fundamental bounds on their predictability. We conclude that while delta "weather" (precise configuration) is unpredictable in the long-term, delta "climate" (statistical behavior) is predictable.

Development of a novel mammalian display system for selection of antibodies against membrane proteins.

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD ) as low as 0.8 nm We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule-positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Malignancy and infection risk during adalimumab therapy in hidradenitis suppurativa.

BACKGROUND: The association of adalimumab therapy with malignancy and infection is established in other inflammatory diseases; however, rates of hidradenitis suppurativa (HS) are based on case reports or retrospective healthcare data and the effect of adalimumab therapy on these rates is unknown. Previously reported rates in the PIONEER OLE Phase 3 study reported on rates only in a subpopulation of 88 participants rather than the entire cohort. AIM: To quantify rates of malignancy and serious infection in all patients with HS treated with adalimumab 40 mg weekly. METHODS: Reanalysis was undertaken of individual patient data from the PIONEER 1, PIONEER 2 and PIONEER open-label extension Phase 3 trial data encompassing 591 unique patients with HS administered adalimumab 40 mg weekly without concurrent antibiotic exposure. Incidence rates of serious infection and malignancy were calculated. RESULTS: Incidence rates of serious infection and malignancy were 2.14 and 0.46 per 100 patient-years, respectively. Rates of infection and malignancy were comparable to those in other inflammatory conditions examined. CONCLUSION: Incidence of serious infection in patients with HS on adalimumab is comparable to those with psoriasis and inflammatory arthropathies, but the incidence of malignancy is increased. This may reflect disease-specific malignancy risk rather than an effect of adalimumab.

Should all community mental health teams be sectorised?

OBJECTIVES: Sectorised catchment areas have characterised Irish mental health service delivery since the devolution of institutional care. Unlike other catchment areas, the Cluain Mhuire Community Mental Health Service (CMCMHS) never sectorised. With the development of Community Health Networks (CHNs) and Primary Care Centres, the CMCMHS has come under renewed pressure for structural change. We aimed to consider the implications of these proposed changes on staff and service users. METHOD: We obtained demographic information comparing the CHNs with respect to attendee numbers, new referrals and admissions over a 1- year period. Secondly, we conducted an anonymous survey seeking opinions on the proposals to switch to a sector-based model and/or specialist inpatient care. RESULTS: Referral and admission rates differed across CHNs, broadly consistent with populations. About 36% of staff and 33% of service users supported changing to a sector-based system. In the event of a sector-based system of care being implemented, 66% of service users felt that existing service users should remain under the care of their current team. There was little support among any group for the development of specialist inpatient teams. CONCLUSIONS: We discuss the benefits and drawbacks of sectorisation of mental health service provision. Most patients did not want to change teams either as current service users or as re-referrals (indicating it will take a significant time to transition to a sector-based system). Without clear pathways towards integration with primary care teams, the advantages of sectorisation may not outweigh the challenges associated with its implementation.

The 2017-19 activity at Mount Agung in Bali (Indonesia): Intense unrest, monitoring, crisis response, evacuation, and eruption.

After 53 years of quiescence, Mount Agung awoke in August 2017, with intense seismicity, measurable ground deformation, and thermal anomalies in the summit crater. Although the seismic unrest peaked in late September and early October, the volcano did not start erupting until 21 November. The most intense explosive eruptions with accompanying rapid lava effusion occurred between 25 and 29 November. Smaller infrequent explosions and extrusions continue through the present (June 2019). The delay between intense unrest and eruption caused considerable challenges to emergency responders, local and national governmental agencies, and the population of Bali near the volcano, including over 140,000 evacuees. This paper provides an overview of the volcanic activity at Mount Agung from the viewpoint of the volcano observatory and other scientists responding to the volcanic crisis. We discuss the volcanic activity as well as key data streams used to track it. We provide evidence that magma intruded into the mid-crust in early 2017, and again in August of that year, prior to intrusion of an inferred dike between Mount Agung and Batur Caldera that initiated an earthquake swarm in late September. We summarize efforts to forecast the behavior of the volcano, to quantify exclusion zones for evacuations, and to work with emergency responders and other government agencies to make decisions during a complex and tense volcanic crisis.

Models of infiltration into homogeneous and fractal porous media with localized sources.

We study a random-walk infiltration (RWI) model, in homogeneous and in fractal media, with small localized sources at their boundaries. In this model, particles released at a source, maintained at a constant density value, execute unbiased random walks over a lattice; a model that represents solute infiltration by diffusion into a medium in contact with a reservoir of fixed concentration. A scaling approach shows that the infiltrated length, area, or volume evolves in time as the number of distinct sites visited by a single random walker in the same medium. This is consistent with numerical simulations of the lattice model and exact and numerical solutions of the corresponding diffusion equation. In a Sierpinski carpet, the infiltrated area is expected to evolve as t^{D_{F}/D_{W}} (Alexander-Orbach relation), where D_{F} is the fractal dimension of the medium and D_{W} is the random-walk dimension; the numerical integration of the diffusion equation supports this result with very good accuracy and improves results of lattice random-walk simulations. In a Menger sponge in which D_{F}>D_{W} (i.e., a fractal with a dimension close to 3), a linear time increase of the infiltrated volume is theoretically predicted and confirmed numerically. Thus, no evidence of fractality can be observed in measurements of infiltrated volumes or masses in media where random walks are not recurrent, although the tracer diffusion is anomalous. We compare our findings with results for a fluid infiltration model in which the pressure head is constant at the source and the front displacement is driven by the local gradient of that head. Exact solutions in two and three dimensions and numerical results in a carpet show that this type of fluid infiltration is in the same universality class of RWI, with an equivalence between the head and the particle concentration. These results set a relation between different infiltration processes with localized sources and the recurrence properties of random walks in the same media.

Sporadic pemphigus foliaceus and class II human leucocyte antigen allele associations in the white British and Indo-Asian populations in the UK.

BACKGROUND: Pemphigus foliaceus (PF) has both genetic and environmental susceptibility factors. Current data on human leucocyte antigen (HLA) in patients with sporadic PF are limited. AIM: To better define the distribution of HLA alleles in patients with PF in the UK. METHODS: We recruited 36 patients [26 of white British (WB) descent, 10 of Indo-Asian (IA) descent] with PF who were living in the UK and 159 ethnically matched normal controls, and analysed their class II HLA DRB1 and DQB1 allele distribution. RESULTS: There was an increased frequency of DRB1*1404 in association with DQB1*0503 in IA patients with PF. The DRB1*04 allele group as a whole had an increased frequency (P < 0.001) in the WB patient group compared with controls. The alleles contributing to this significance were DRB1*0401 (P = 0.03) and DRB1*0404 (P < 0.01). CONCLUSION: This is the largest HLA association study in sporadic PF from the UK to date. There appears to be a difference in PF susceptibility alleles between WB and IA patients, highlighting the importance of racial variation in genetic susceptibility to disease development.

Plastic Surgery Inclusion in the Undergraduate Medical Curriculum: Perception, Challenges, and Career Choice-A Comparative Study.

OBJECTIVE: The undergraduate medical curriculum has been overcrowded with core learning outcomes with no formal exposure to plastic surgery. The aim of this study was to compare medical students from two educational settings for the basic understanding, preferred learning method, and factors influencing a career choice in plastic surgery. DESIGN AND SETTING: A prospective cohort study based on a web-based anonymous questionnaire sent to final year medical students at Birmingham University (United Kingdom), McGill University (Canada), and a control group (non-medical staff). The questions were about plastic surgery: (1) source of information and basic understanding; (2) undergraduate curriculum inclusion and preferred learning methods; (3) factors influencing a career choice. A similar questionnaire was sent to non-medical staff (control group). The data was analysed based on categorical outcomes (Chi-square χ2) and level of significance p ≤ 0.05. RESULTS: Questionnaire was analysed for 243 students (Birmingham, n = 171/332, 52%) (McGill n = 72/132, 54%). Birmingham students (14%) considered the word "plastic" synonymous with "cosmetic" more than McGill students (4%, p < 0.025). Teaching was the main source of knowledge for McGill students (39%, p < 0.001) while Birmingham students and control group chose the media (70%, p < 0.001). McGill students (67%) more than Birmingham (49%, p < 0.010) considered curriculum inclusion. The preferred learning method was lectures for McGill students (61%, p < 0.01) but an optional module for Birmingham (61%). A similar proportion (18%) from both student groups considered a career in plastic surgery. CONCLUSIONS: Medical students recognised the need for plastic surgery inclusion in the undergraduate curriculum. There was a difference for plastic surgery source of information, operations, and preferred method of learning for students. The study highlighted the urgent need to reform plastic surgery undergraduate teaching in collaboration with national educational bodies worldwide.

Key Matrix Proteins Within the Pancreatic Islet Basement Membrane Are Differentially Digested During Human Islet Isolation.

Clinical islet transplantation achieves insulin independence in selected patients, yet current methods for extracting islets from their surrounding pancreatic matrix are suboptimal. The islet basement membrane (BM) influences islet function and survival and is a critical marker of islet integrity following rodent islet isolation. No studies have investigated the impact of islet isolation on BM integrity in human islets, which have a unique duplex structure. To address this, samples were taken from 27 clinical human islet isolations (donor age 41-59, BMI 26-38, cold ischemic time < 10 h). Collagen IV, pan-laminin, perlecan and laminin-α5 in the islet BM were significantly digested by enzyme treatment. In isolated islets, laminin-α5 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident during culture. Collagen IV and pan-laminin were present in the disorganized BM of isolated islets, yet a significant reduction in pan-laminin was seen during the initial 24 h culture period. Islet cytotoxicity increased during culture. Therefore, the human islet BM is substantially disrupted during the islet isolation procedure. Islet function and survival may be compromised as a consequence of an incomplete islet BM, which has implications for islet survival and transplanted graft longevity.

Substrate Specificity Profiling of Histone-Modifying Enzymes by Peptide Microarray.

The dynamic addition and removal of covalent posttranslational modifications (PTMs) on histone proteins serves as a major mechanism regulating chromatin-templated biological processes in eukaryotic genomes. Histone PTMs and their combinations function by directly altering the physical structure of chromatin and as rheostats for effector protein interactions. In this chapter, we detail microarray-based methods for analyzing the substrate specificity of lysine methyltransferase and demethylase enzymes on immobilized synthetic histone peptides. Consistent with the "histone code" hypothesis, we reveal a strong influence of adjacent and, surprisingly, distant histone PTMs on the ability of histone-modifying enzymes to methylate or demethylate their substrates. This platform will greatly facilitate future investigations into histone substrate specificity and mechanisms of PTM signaling that regulate the catalytic properties of histone-modifying enzymes.

The challenges of diagnosis and treatment of dementia in Down's syndrome.

OBJECTIVES: People with Down syndrome (DS) are at high risk for developing dementia and early diagnosis is vital in enhancing quality of life. Our aim was to compare our practice to consensus recommendations on evaluation, diagnosis and pharmacological treatment of individuals with DS who develop dementia. We also aimed to establish the average time taken to make a diagnosis of dementia and to commence pharmacotherapy, and to assess tolerability to acetylcholinesterase inhibitors. METHODS: Retrospective chart review in an exhaustive sample containing all current service users attending our service with DS and a diagnosis of dementia (n=20). RESULTS: The sample was 75% female and 70% had a moderate intellectual disability. The average age at diagnosis of dementia was 52.42 years old. The average time to diagnosis from first symptom was 1.13 years and the average time to commence pharmacotherapy was 0.23 years. A total of 17 patients commenced on acetylcholinesterase inhibitors, and of these seven discontinued medication due to side-effects or lack of efficacy. CONCLUSIONS: The results on anticholinesterases add to the limited pool of data on treatment of dementia in DS. There was an identified need to improve the rates of medical, vision and hearing assessments, and prospective screening. Deficiencies in screening and diagnosis may be addressed by implementing a standardised dementia assessment pathway to include prospective screening and longitudinal assessment using easily administered scales. We highlight the importance of improving the diagnostic process, as a vital window of opportunity to commence a comprehensive care plan may be lost.

Can we ease the financial burden of colonoscopy? Using real-time endoscopic assessment of polyp histology to predict surveillance intervals.

BACKGROUND: Polyps identified at colonoscopy are predominantly diminutive (<5 mm) with a small risk (>1%) of high-grade dysplasia or carcinoma; however, the cost of histological assessment is substantial. AIM: The aim of this study was to determine whether prediction of colonoscopy surveillance intervals based on real-time endoscopic assessment of polyp histology is accurate and cost effective. METHODS: A prospective cohort study was conducted across a tertiary care and private community hospital. Ninety-four patients underwent colonoscopy and polypectomy of diminutive (≤5 mm) polyps from October 2012 to July 2013, yielding a total of 159 polyps. Polyps were examined and classified according to the Sano-Emura classification system. The endoscopic assessment (optical diagnosis) of polyp histology was used to predict appropriate colonoscopy surveillance intervals. The main outcome measure was the accuracy of optical diagnosis of diminutive colonic polyps against the gold standard of histological assessment. RESULTS: Optical diagnosis was correct in 105/108 (97.2%) adenomas. This yielded a sensitivity, specificity and positive and negative predictive values (with 95%CI) of 97.2% (92.1-99.4%), 78.4% (64.7-88.7%), 90.5% (83.7-95.2%) and 93% (80.9-98.5%) respectively. Ninety-two (98%) patients were correctly triaged to their repeat surveillance colonoscopy. Based on these findings, a cut and discard approach would have resulted in a saving of $319.77 per patient. CONCLUSION: Endoscopists within a tertiary care setting can accurately predict diminutive polyp histology and confer an appropriate surveillance interval with an associated financial benefit to the healthcare system. However, limitations to its application in the community setting exist, which may improve with further training and high-definition colonoscopes.

False-negative BD MGIT™ TBc Identification Test results in routine tuberculosis diagnosis: a New Zealand perspective.

>We previously reported on a comparison of the AccuProbe(®) Gen-Probe(®) MTBC assay (AccuProbe) (BioMérieux, Marcy L'Etoile, France) with the Becton Dickinson (BD) MGIT™ TBc Identification (TBc) Test (BD, Franklin Lakes, NJ, USA) in our laboratory. In the period following the shift from the AccuProbe assay to the TBc test, we obtained six false-negative results. On sequencing the mpt64 gene, we found that these false-negative cases had mutations in the mpt64 gene due to deletion, insertion or substitution. Despite the occurrence of false-negative results, we found that the reduced cost and minimal technical expertise, combined with a new testing algorithm, still make this test the preferred option for rapidly identifying Mycobacterium tuberculosis complex in MGIT cultures in a low TB burden country such as New Zealand.

The clinical spectrum of de novo donor-specific antibodies in pediatric renal transplant recipients.

The development of donor-specific HLA antibodies (DSA) is associated with worse renal allograft survival in adult patients. This study assessed the natural history of de novo DSA, and its impact on renal function in pediatric renal transplant recipients (RTR). HLA antibodies were measured prospectively using single-antigen-bead assays at 1, 3, 6 and 12 months posttransplant followed by 12-monthly intervals and during episodes of allograft dysfunction. Of 215 patients with HLA antibody monitoring, 75 (35%) developed DSA at median of 0.25 years posttransplant with a high prevalence of Class II (70%) and HLA-DQ (45%) DSA. DSA resolved in 35 (47%) patients and was associated with earlier detection (median, inter-quartile range 0.14, 0.09-0.33 vs. 0.84, 0.15-2.37 years) and lower mean fluorescence intensity (MFI) (2658, 1573-3819 vs. 7820, 5166-11 990). Overall, DSA positive patients had more rapid GFR decline with a 50% reduction in GFR at mean 5.3 (CI: 4.7-5.8) years versus 6.1 (5.7-6.4) years in DSA negative patients (p = 0.02). GFR decreased by a magnitude of 1 mL/min/1.73 m(2) per log10 increase in Class II DSA MFI (p < 0.01). Using Cox regression, independent factors predicting poorer renal allograft outcome were older age at transplant (hazard ratio 1.1, CI: 1.0-1.2 per year), tubulitis (1.5, 1.3-1.8) and microvasculature injury (2.9, 1.4-5.7). In conclusion, pediatric RTR with de novo DSA and microvasculature injury were at risk of allograft failure.