Background; Both herpetic pain and itching in shingles are two symptoms whose pathogenesis has not been elucidated, although they are thought to be due to nerve damage. These two symptoms are difficult to treat and negative impact quality of life. In addition, It is unclear which patient will have the symptoms of itching or pain. Vitamin B 12 is a neurotropic agent which is contributes to the treatment of nerve damage, and effective in treating neuropathic pain and itch. In this study we investigated that is relationship between vitamin B12 both herpetic pain and herpetic itch. Methods; In this study, we investigated the effect of vitamin B12 values on itching and pain symptoms that patients with shingles have in the acute period. Vitamin B 12 values of 53 adults with patients with shingles with herpetic pain or herpetic itching were recorded and compared with the control group. Results; We found that patients with herpetic pain had lower vitamin B12 values than the control group (p=0.046) and patients with herpetic itch (p=0.021). Vitamin B12 values of herpetic itch patients did not show significant difference from the control group (p=0.816). Conclusions; Although vitamin B12 deficiency plays a role in the etiology of herpetic pain, it has no effect on herpetic itching. Our study supports that the etiopathogenesis of HI is different from herpetic pain, and will help studies focusing on herpetic itching etiopathogenesis.

Purpose: We aimed to investigate the relationship between the staining rates of thrombospondin-1, VEGF and PDGFR-in tissue preparations in patients diagnosed with DLBCL as a result of lymphadenopathy biopsy and their clinical features at the time of diagnosis, response to treatment and prognosis. Materials and Methods: For this purpose, a total of 44 patients with a diagnosis of DLBCL, 24 male and 20 female, and 13 patients diagnosed with control reactive lymphadenopathy, 6 male and 7 female were enrolled. After the pathology preparations of the patient and control groups were stained immunohistochemically with VEGF, PDGFR-β, thrombospondin-1 stains, the clinical characteristics of the patients and the relationship between survival analysis and staining rates were analyzed statistically. Results: When the patients were compared with the control group in terms of VEGF, PDGFR-β, thrombospondin-1 staining rates, we found that staining with PDGFR-β was lower in patients (p = 0.009). Although it was not statistically significant for PDGFR-β, it was observed that 5-year OS and PFS values were low in patients with high levels of expression, on the contrary, 5-year OS was low in patients with high thrombospondin staining rate. A negative correlation was seen between thrombospondin-1 and PDGFR-β (p=0.003, r=-0.440). Conclusion: As a result, although no relationship was found between VEGF and survival in our study, it was observed that PDGFR-β and thrombospondin-1 were effective in prognosis. A negative correlation was seen between thrombospondin-1 and PDGFR-β.

Species invasion represents one of the major drivers of biodiversity change globally, yet there is widespread confusion about the nature of non-indigenous species (NIS) impact. This stems from differing notions of what constitutes invasive species ‘impact’ and the scales at which it should be assessed. At local scales, the mechanisms of impact on competitors can be classified into four scenarios: 1) minimal impact from NIS inhabiting unique niche space; 2) neutral impact spread across the community and proportional to NIS abundance; 3) targeted impact on a small number of competitors with overlapping niches; and 4) pervasive impact that is disproportionate to NIS abundance and caused by modifications that filter out other species. I developed a statistical test to distinguish these four mechanisms based on community rank-abundance curves and then created a scale-independent standardized impact score. Using an example long-term dataset, that has high native plant diversity and an abundance gradient of the invasive vine, Vincetoxicum rossicum, I show that impact resulted in either targeted extirpations or widespread biodiversity loss. Regardless of whether NIS impact is neutral, targeted or pervasive, the net outcome will be the homogenization of ecosystems and reduced biodiversity at larger scales, perhaps reducing ecosystem resilience.

Object: Our aim is to evaluate the elevation of pancreatic enzymes in COVID-19 patients and their relationship with severity of COVID-19. Method: In this study, 1378 patients with COVID-19 infection were included. Relation of elevated amylase and lipase levels and co-morbid conditions with the severity of COVID-19 were checked. The effect of hemodynamic parameters and organ failures on pancreatic enzymes and their relations with prognosis were statistically analyzed. Results: There were 678 (%49,2) female patients and 700 (50,8%) male patients. Of all patients, 687 (49,9%) had mild, 691 (50,1%) severe COVID-19 infections. Elevated amylase levels were detected in 23% of patients (n:316). 19% (261) of them had a slight (1-3 times) increase in amylase levels, while 4% (55) had a more than 3 times increase in amylase than normal. Only 6% of patients with elevated amylase leves had the acute pancreatitis according to Atlanta criteria. According to univariate and multivariate analyses, elevated amylase levels was found statistically related with severity of COVID-19 (OR:4,37-p <0,001). And also diabetes mellitus (DM) (OR:1,82-p:0,001), kidney failure (OR:5,18- p< 0,001), liver damage (OR:6,63 p < 0,001), hypotension (OR:6,86-p< 0,001), sepsis (OR:6,20-p:0.008) were found to related to death of COVID-19. Conclusions: Elevated pancreatic enzyme levels in COVID-19 infections is to related to severity of COVID-19 infection and hemodynamic instability. Similar to other organs, the pancreas can be affected by severe COVID-19 infection.

Skeletal involvement in CLL is very rare. We present a case of ileum bone lesion during in a patient receiving 5th line of therapy. Despite radiotherapy and salvage therapies, subsequent bone lesions led to a fatal outcome. Further studies on the mechanism by which bone disease develops are currently needed.

Objective: Congenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology and enhance telomere length (TL) shortening. We aim to study the association between periconception maternal TL, as future predictive biomarker, and the risk of having a child with COD. Design: HAVEN-study, a multicenter case-control triad study conducted in the Netherlands. Setting and population: 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Methods: TL was estimated, on DNA from venous blood samples, by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios (OR) per standard deviation (SD) decrease between maternal T/S ratio and COD and VSD risk. Main outcome measures: The risk of COD in offspring. Results: A significant association was shown between maternal TL shortening (per standard deviation) and a 29% increased risk of VSD in offspring (OR 1.29(95% CI 1.04-1.61), P= 0,02), which remained significant after additional adjustment for maternal age (adjOR 1.25(95% CI 1.01-1.55), P= 0,04). No association between maternal TL and the risk of overall COD in offspring was observed. Conclusion: Shortening of maternal TL, due to maternal conditions including age, is associated with an approximately 1.3-fold increased risk, per SD in TL-shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.

\cite{redirecting}La frequente domanda di risorsa idrica porta ad una necessità di depurare l'acqua con maggiore efficienza cercando di favorire il riutilizzo dell'acqua per uso agricolo o industriale. I sistemi convenzionali sono diventati obsoleti perché non riescono più a garantire il rispetto delle norme sulle concentrazioni di inquinanti per il riutilizzo della risorsa. Negli anni, la ricerca scientifica ha sviluppato un impianto di trattamento a membrana (MBR) in grado di ottenere un efficacia di trattamento elevata grazie al processo di filtrazione su membrana, ma la diffusione è stata limitata a causa dei costi iniziali e di gestione dell'impianto e a causa del fenomeno del fouling, cioè lo sporcamento della membrana. Per risolvere questi problemi, sono state sperimentate membrane dinamiche autoformanti, cioè membrane composte da materiale di supporto in grado di utilizzare il fouling a favore per migliorare l'efficienza depurativa. Un altro vantaggio si ottiene con l'applicazione di processi elettrochimici che migliorano la mitigazione del fouling e le proprietà dell'effluente. In questa attività è stata osservata l'efficienza depurativa di un bioreattore a membrana dinamica autoformante incapsulata combinato con i processi elettrochimici (e-ESFDMBR) a scala pilota utilizzando un refluo reale.

Surface water storage—including wetlands and other small waterbodies—has largely been disregarded in traditional hydrological models. In this paper, the grid resampling method is adopted to study the influence of the digital elevation model (DEM) grid resolution on depression storage (DS) considering different rainfall return periods. It is observed that the DEM grid size highly affects DS, and the higher the grid resolution is, the larger the DS value. However, when the grid resolution reaches a certain value, the maximum DS value decreases. This suggests that a critical grid resolution value exists at which the water storage capacity of depressions is maximized, namely, 20 m in this work. This phenomenon is further verified in two test cases with and without the infiltration process, i.e., calculations of the local area and without infiltration area, respectively. This research may facilitate the accurate computation of the DS process, which is greatly affected by the grid resolution, thereby improving the reliability of hydrological models.

The Budyko framework, which can describe a simple but useful partitioning of precipitation under supply and energy limits, is used widely to estimate evapotranspiration (ET). Previous studies have investigated time-variant Budyko functions on annual or interannual scales but seldom on the intra-annual scale. This study used a monthly two-parameter ( κ and y0) Budyko function and three schemes that considered single observations (ET or streamflow (Q)) and dual observations (ET and Q) to assimilate the time-varying parameters using the ensemble Kalman filter method. The study considered the contiguous USA (CONUS) using the Model Parameter Estimation Experiment dataset. The time-varying parameters were explained on the basis of time series analysis and correlation with meteorological data. Three conclusions were as follows. (1) The identified time-varying parameters ( κ and y0) of the Budyko function could effectively simulate ET. (2) The assimilation using only ET observations could identify a plausible set for parameter κ but was inadequate for y0 . (3) Most time-varying parameters exhibited a 12-month period, and the trend and change points detected for Midwest CONUS were related to anthropogenic influences such as extraction and use of groundwater. The findings show that changing environment can be detected by using the proposed time-varying parameters of the Budyko function.

Faced with the anthropic activities of urban streams stretches through rectification with concrete, there is a concern about the modifications of the aquatic habitats and consequent ecological damages to the ecosystems. Based on biophilic engineering, there is a great opportunity to idealize and test interventions to revitalize such hampered ecosystems. Hence, we verified the performance of biological and organic factors, after the implementation of one-off interventions in three rivers using biophilic handmade materials and structural elements in their fixation. We carried out the project in urban stretches of concrete bed streams, located in Sorocaba-SP, Southeast of Brazil. In two years, we conducted biweekly in situ and laboratory measurements to characterize the study sites, idealize, scale, implement the projects, and, evaluate the ecological responses of the implementations. We collected sampling in two points: upstream and downstream interventions. We evaluated the performance of the interventions through the analysis of SWOT (Strengths, Weaknesses, Opportunities, and Threats) factors and by using the Analytic Hierarchy Process (AHP). We presented the results through a decision-making matrix for stakeholders, which indicated that our ideas are of low cost and easy to implement. Then, we got the following scenario of SWOT priorities: opportunity (58.55%), strength (24.71%), threat (10.74%), and weakness (6.00%). They demand constant efforts for maintenances and they need adjustments to a better understood by residents and the watershed management. We concluded that the strengths observed in the project turn our idea replicable in any part because it attaches the idea of caring about the environment through biophilic techniques, and the weaknesses are liable to modifications (improvements) in future projects that consider such proposal.

Geonor T-200B weighing precipitation gauge (Geonor) and Chinese standard precipitation gauge (CSPG) are widely used for measuring precipitaion in the Qinghai-Tibet Plateau. However, their measurements must be adjusted due to wetting, evaporation loss and wind-induced undercatch. Some transfer functions had been proposed in previous studies, but their applicability in the Qinghai-Tibetan Plateau has not been evaluated. In our study, a precipitation measurement intercomparison experiment was carried out from August 2018 to September 2020 at a station in the central Qinghai-Tibet Plateau, and these transfer functions are also evaluated based on the results of the experiment. The results show that: (1) the catch efficiency of Geonor for rain, mixed, snow, hail are 92.06%, 85.32%, 68.08% and 91.82% respectively, and the catch efficiency of CSPG are 92.59%, 81.32%, 46.43% and 95.56% respectively. (2) K2017b has the most accurate correction results for Geonor solid and mixed precipitation at 30 minutes time scale, and the M2007e scheme has the most accurate correction results for Geonor solid precipitation at event scale. (3) The current transfer functions for CSPG underestimate the solid precipitation, while overestimate the liquid precipitation. Based on the results of the comparative observation in our study, new CSPG transfer functions are proposed for the central Qinghai-Tibet Plateau. (4) Hail is also an important precipitation type in the central Qinghai-Tibet Plateau. Because the capture rate of hail precipitation is close to that of rain, and the temperature when hail precipitation occurs is high, it is not necessary to determine the hail precipitation type, and the transfer functions recommended in this study can also get a good correction results.

Silent RSV in infants with SARS‑CoV‑2 infection: a case seriesAntonietta Giannattasio, MD, PhD1, Marco Maglione, MD, PhD1, Carolina D’Anna, MD1, Stefania Muzzica, MD1,Francesca Angrisani, MD1, Sabrina Acierno, MD1, Alessandro Perrella2, MD, PhD2, Vincenzo Tipo, MD11Santobono-Pausilipon Children’s Hospital, Pediatric Emergency and Short Stay Unit, Naples, Italy2Cardarelli Hospital, Infectious Disease-Health Policy Direction, Naples, Italy

Detecting fat globules in blood in diagnosing fat embolism syndrome (FES) remains controversial. This case illustrated two life threatening episodes possibly due to FES, with a dramatic increases of fat globules in blood. Significance of quantitative change of fat in blood in diagnosing FES should be evaluated in the future.

In South Vietnam, live bird markets (LBMs) are key in the value chain of poultry products and spread of avian influenza virus (AIV) although they may not be the sole factor to determine avian influenza (AI) prevalence in the southern part. Therefore, a risk analysis of AIV spread was conducted by including all possible value chain factors. A cross-sectional study was performed in backyard farms, high-biosecurity farms (bio-farms), LBMs, and poultry delivery stations (PDSs) in the four districts of Vinh Long Province in December 2016 and August 2017. A total of 3 597 swab samples were collected from individual poultry at 101 backyard farms, 50 bio-farms, 58 sellers in LBMs, and 17 traders in PDSs and then investigated for AIV isolation. Concurrently, information related to participants and birds was collected and used to identify the fixed and random effects of factors in AIV infection. A total of 274 birds were positive for virus isolation, with a prevalence of 7.6% (95% confidence interval [CI]: 6.8–8.5) at the individual poultry level, and the adjusted prevalence based on the sampling weight was 7.9% (95% CI: 7.6–8.2). The significantly higher prevalence in PDSs (20.7%) and LBMs (14.2%) compared to backyard farms (3.0%) and bio-farms (0.6%) suggested that PDSs are another hot spot for AIV circulation. The high diversity in the seller and trader population characteristics was revealed using multiple-correspondence analysis to analyze the participants’ demographic factors in LBM and PDS. The mixed-effect logistic regression model revealed that keeping duck at the sampling time and the owner’s older age should be risk factors of AIV infection in PDS. Therefore, functional AI control efforts to monitor the PDS system should be emphasized to minimize AIV circulation risk in Vietnam.

Objective: To determine the association between treatment of persistent BV in pregnancy and risk for spontaneous preterm birth (sPTB). Design: The retrospective data from IBM® MarketScan® Commercial Database was analyzed. Setting: United States outpatient data. Population or Sample: Women aged 12–55 years with a singleton gestation. Methods: Women were linked to an outpatient medications database and medications taken during the pregnancy were analyzed. Treatment of BV in pregnancy was defined as a diagnosis of BV and treatment with Metronidazole and/or Clindamycin, and persistent treatment of BV was defined as BV in more than 1 trimester or BV requiring more than 1 antibiotic prescription. Odds ratios were calculated comparing sPTB in those with BV and persistent BV to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. Main outcome measures: sPTB Results: Among a cohort of 2,538,606 women, 216,611 had an associated ICD-9 or ICD-10 code for diagnosis of BV alone, and 63,817 had BV and were treated with either metronidazole and/or clindamycin. The sPTB rate among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% CI 1.52, 1.81]) or those with 3 or more prescriptions in pregnancy (1.48 [95% CI 1.35, 1.63]. Conclusions: Treatment of persistent BV is associated with increased sPTB risk.

Objetive: To evaluate the ultrasonographic contractile activity indices of the diaphragm in infants with moderate and severe bronchiolitis supported with high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV) to predict the need of invasive mechanical ventilation (IMV). Methods: Prospective observational study in infants admitted to a Pediatric Intensive Care Unit (PICU). Diaphragmatic excursion (dEx), diaphragmatic inspiratory (dTi) and expiratory time (dTe), and fraction of diaphragmatic thickening (dTF) were recorded at admission, 24 h and 48 h in both diaphragms. RESULTS: Twenty-six patiens were included (14 on HFNC and 12 on NIV) with a total of 56 ultrasonographic evaluations. Three patients required IMV. Sixty-four percent of the patients on HFNC required NIV as rescue therapy and 2/14 IMV (14,2%). In the HFNC group there were no differences in dEx between those who required escalation to NIV or IMV and those who didn’t. Diaphragmatic left thickening fraction (Left dTF) increased in patients on HFNC requiring IMV vs those needing NIV (Left dTF 47% vs 22% (13-30); p=0,046, r=0,7) (Fig 2). Diaphragmatic inspiratory time was higher in infants on HFNC requiring IMV and diaphragmatic expiratory time was shorter (dLET, p=0,038; dRET, p=0,022). In the NIV group there were no diffenreces in dEx, dTi, dTe or dTF between patients needing escalation to IMV and those who didn’t. We found no correlation between a clinical score and echographic dTF. CONCLUSION: In infants with moderate or severe brochiolitis receiving HFNC the use of ultrasonographic left dTF could help predict respiratory failure (RF) and need for IMV. The use of ultrasonographic diaphragmatic excursion is of little help to predict both.

BACKGROUND: Workplace burnout can result in negative consequences for clinicians and patients. We assessed burnout prevalence and sources among pediatric hematology/oncology inpatient nurses, ambulatory nurses, physicians (MDs), and advanced practice providers (APPs) by evaluating effects of job demands and involvement in patient safety events (PSEs). METHODS: A cross-sectional survey (Maslach Burnout Inventory) measured emotional exhaustion, depersonalization, and reduced personal accomplishment. The NASA Task Load Index measured mental demand, physical demand, temporal demand, effort, and frustration. Relative weights analyses estimated the unique contributions of tasks and PSEs on burnout. Post-hoc analyses evaluated open-response comments for burnout factors. RESULTS: Burnout prevalence was 33%, 20%, 34% and 33% in inpatient nurses, ambulatory nurses, and MD, and APPs respectively (N=481, response rate 69%). Reduced personal accomplishment was significantly higher in inpatient nurses than MDs & APPs. Job frustration was the most significant predictor of burnout across all four cohorts. Other significant predictors of burnout included temporal demand (nursing groups & MDs) effort (inpatient nurses & MDs) and PSE involvement (ambulatory nurses). Open-response comments identified time constraints, lack of administrator support, insufficient institutional support for self-care, and inadequate staffing and/or turnover as sources of frustration. CONCLUSIONS: All four clinician groups reported substantial levels of burnout, and job demands predicted burnout. The body of knowledge on job stress and workplace burnout supports targeting organizational-level sources, versus individual-level factors, as the most effective prevention and reduction strategy. This study elaborates on this evidence by identifying structural drivers of burnout within a multidisciplinary context of pediatric hematology/oncology clinicians.

Dietary diversity during infancy and the association with childhood food allergen sensitization Authors: Kate Maslin PhD1,2, Kaci Pickett MSc3, Suzanne Ngo3,4 MD, William Anderson3,4 MD, Taraneh Dean PhD2,5, Carina Venter PhD2,3,4School of Nursing and Midwifery, University of Plymouth, Plymouth, UK.The David Hide Asthma and Allergy Centre, St. Mary’s Hospital, Isle of Wight, UKUniversity of Colorado School of Medicine, Colorado, USAAllergy and Immunology Section, Children’s Hospital Colorado, Colorado, USAUniversity of Brighton, Brighton, UKRunning title: Dietary diversity and food sensitization

The format of science papers and articles now have hardly changed since the 17th century, even though research methods and published content have evolved immensely. Why do scientists produce innovative modern-day research, but still publish it in a 400-year-old format? What can we do to produce scientific articles ‘of the future’ that better serve the global, collaborative, and data-rich science of the 21st century?Alberto Pepe, Senior Director, Strategy and Innovation, Atypon and Matteo Cavalleri, Publisher, Wiley will be discussing Wiley’s vision of the scientific article, and how preprints, interactive figures, multimedia elements and code integration are innovating scholarly publications.Part of Wiley Research APAC Webinars, recording available (free registration required) here.

A Majorana fermion is the single fermionic particle that is its own antiparticle. Its dynamics is determined by the Majorana equation, where the spinor field is by definition equal to its charge-conjugate field. In this paper, we investigated Shannon’s entropy of linear Majorana fermions to understand how this quantity is modified due to an external potential of the linear type linear. Subsequently, we turn our attention to the construction of an ensemble of these Majorana particles to study the thermodynamic properties of the model. Finally, we show how Shannon’s entropy and thermodynamic properties are modified under the linear potential action. KEYWORDS: Majorana Fermions; Thermodynamic properties; Shannon’s Entropy.

Proning in Pregnancies Complicated by Acute Respiratory Distress Syndrome. A Call to Action During the COVID-19 Pandemic.Authors: L Cojocaru, OM Turan, A Levine, L Sollecito, S Williams, E Elsamadicy, S Crimmins, S Turan.Liviu Cojocaru, MD: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science. University of Maryland School of Medicine, Baltimore, MD, USA.(lcojocaru@som.umaryland.edu) (ORCID No: 0000-0003-1558-702X).Ozhan M Turan, MD, Ph.D.: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science. University of Maryland School of Medicine, Baltimore, MD, USA.(oturan@som.umaryland.edu)Andrea Levine, MD: Division of Pulmonary and Critical Care Medicine. Department of Medicine. University of Maryland School of Medicine, Baltimore, MD, USA.(andrea.levine@som.umaryland.edu)Linda Sollecito, BSN, RN, CCRN: Medical Intensive Care Unit. University of Maryland Medical Center, Baltimore, MD, USA.(lsollecito@umm.edu)Susan Williams, MS, RN, CCRN: Medical Intensive Care Unit. University of Maryland Medical Center, Baltimore, MD, USA.(susanwilliams@umm.edu)Emad Elsamadicy, MD: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science. University of Maryland School of Medicine, Baltimore, MD, USA.(eelsamadicy@som.umaryland.edu)Sarah Crimmins, DO: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science. University of Maryland School of Medicine, Baltimore, MD, USA.(scrimmins@som.umaryland.edu)Shifa Turan, MD, RDMS: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science. University of Maryland School of Medicine, Baltimore, MD, USA.(sturan@som.umaryland.edu)Correspondence to: Liviu Cojocaru, MD: Division of Maternal-Fetal Medicine. Department of Obstetrics, Gynecology and Reproductive Science, University of Maryland School of Medicine, Baltimore, MD, USA.(lcojocaru@som.umaryland.edu)Disclosures: None.Acknowledgments: We are grateful to Bill Seiler, Erin Rummel, Kelly Kennedy, Alexandra Bessent, Chris Wells, McLellan Shelby, Jessica Peterson, and Amanda Sullivan for assistance in creating the proning video instructions.Short title: Proning in pregnancies complicated by ARDS. It’s time!

Objective: To validate the Weiniger model, a multivariable prediction model for placenta accreta spectrum (PAS). Design: Multicentre external validation study. Setting: Two tertiary care hospitals in the United States. Population: Cohort A included patients with risk factors (prior caesarean delivery, placenta praevia) and/or ultrasound features of PAS (variable risk) presenting to a tertiary care hospital. Cohort B patients were referred to a tertiary care hospital specifically for ultrasound features of PAS (higher risk). Methods: Weiniger model variables (prior caesarean deliveries, placenta praevia and ultrasound features of PAS) were retrospectively collected from both cohorts and predictive performance of the model was evaluated. Main Outcome Measures: Surgical and/or pathological diagnosis of PAS. Results: The model c-statistic in cohorts A and B was 0.728 (95% CI: 0.662, 0.794) and 0.866 (95% CI: 0.754, 0.977) signifying acceptable and excellent discrimination, respectively. Based on calibration curves, the model underestimated average PAS risk in both cohorts. In both cohorts, high risk was overestimated and low risk underestimated. Use of this model compared to a “treat all” strategy had greater net benefit at a threshold probability of > 0.25 in cohort A, but no net benefit in cohort B. Conclusions: This study provides multicentre external validation of the Weiniger model for PAS prediction, making it a useful triaging tool for management of this high-risk obstetric condition. Clinical usefulness of this model is influenced by the incidence of risk factors and PAS ultrasound features, with better performance in a variable-risk population at threshold probability >25%.

Graded home introduction of egg is safe, well received and cost effective when managing childhood egg allergyTo the Editor,In Australia, an IgE mediated allergy to egg is a common food allergy in children.1-2 The 2011 HealthNuts study determined that 8.9% of children in Australia have an egg allergy.1-2IgE mediated allergy to egg can be mild and most children may outgrow this by 4-5 years of age.3-4 Almost 80% of children with IgE mediated egg allergy are tolerant of egg in a baked form with wheat being used as a matrix.1,3 Turner et al. suggests that the outcome of baked egg challenges can be unpredictable and can lead to anaphylaxis even in children with prior mild symptoms.5 Tolerance to baked egg is generally confirmed by a baked egg food challenge in hospital after which patients are encouraged to introduce baked egg products at home.6 Patients are reassessed and subsequently undergo a lightly cooked egg challenge in hospital where resolution is confirmed if successful.6Whereas there is evidence that majority of children with an egg allergy are tolerant to baked egg, there is debate as to whether it can reduce the duration of egg allergy.7-9 Recently, Gotesdyner et al found that a structured graded exposure using baked egg followed by lightly cooked egg compared to complete avoidance helped achieve tolerance to egg.3 Their findings suggest that an egg ladder may promote a faster resolution of egg allergy. However, due to the case control study design and small sample size definite conclusions could not be drawn.3Our Paediatric Allergy Service is a busy tertiary level clinic with more than 2000 outpatient interactions annually. To reduce the burden on tertiary resources, an egg tolerance ladder was developed (Appendix 1). It has been offered to patients considered low risk which includes (but is not limited to) patients with a single food allergy; mild or no eczema; mild, well controlled or no coexisting asthma; and/or a history of IgE mediated egg allergy without anaphylaxis. It has been designed to allow slow introduction of baked egg followed by foods containing small amounts of cooked egg and finally lightly cooked egg at home. Support throughout the home introduction process is provided by the treating team via email and phone contact.The aim of this study was to evaluate the use of this structured “egg ladder” with regards to its safety as well as user satisfaction and barriers that arose in negotiating it. We also attempted to determine potential risk factors which increased likelihood of clinical reaction to foods containing egg and rates of eventual tolerance to lightly cooked and raw egg achieved in the home environment. This study was approved by the Ethics Committee at John Hunter Children’s Hospital (2020/ETH01192).Patients with mild to moderate IgE mediated egg allergy aged 0-18 years seen in the Paediatric Allergy Clinic and commenced on an egg tolerance ladder by the Paediatric Immunologist were recruited retrospectively. Verbal and written education on the use of the ladder had been provided at the time of clinic review. Patients were excluded from home introduction if they had a history of anaphylaxis to any food containing egg or a non-IgE mediated egg allergy.A file audit identified a total of 98 patients for inclusion in this study who had been commenced on the egg ladder between September 2018 and June 2020. Patients were contacted by email and phone, and offered participation in a telephone survey to evaluate the use of the egg tolerance ladder. Almost half (47 patients) consented to the study. At the time of commencing the egg ladder, patients had a mean age of 40 months (IQR: 12-60 months). Six children did not have a skin prick test (SPT). The majority were sensitised with a mean SPT of 3.1mm. Most (66%) had at least one atopic comorbidity and almost half had more than one food allergy. The vast majority (87.2%) of patients commenced the egg ladder at home. This includes 23 patients already tolerant to baked egg prior to clinic presentation, based on clinical history. Only 3 (6%) used the resources of an inpatient challenge.Patients had spent an average of 15.5 months (IQR: 9-21.5 months) on the ladder. At the time of review, 43% of patients had completed the egg ladder but interestingly, four parents believed their child was still allergic to egg. The mean age of commencement on the egg ladder was higher than expected (40 months), and around the age a child is expected to outgrow an allergy to egg.3-4 Despite this, many patients reported reactions while using the egg ladder. A mild reaction was reported by 18 (38%) parents, 16 required treatment and of those one was given adrenaline. This child was 6 years of age, had an isolated egg allergy and small skin test (3.5mm). They reacted to Step 5 and have continued Step 4 at home successfully. Both families reporting a severe reaction recommenced the ladder and were able to subsequently progress successfully to Step 5 or 6. The majority had a mild skin response (rash or hives). Skin testing was a poor differentiator for clinical reaction with 38% of those with negative skin testing reporting a mild reaction with baked egg.Parental satisfaction was high with 78.7% satisfied or very satisfied with the egg ladder. Most of the remaining families were neutral with no families dissatisfied with the ladder use. Many stated that they valued the structured approach of introducing egg which helped identify their child’s level of tolerance, and allowed them to progress at their own pace. A number of parents identified the main barrier to progressing the ladder was the taste and/or texture of egg after successfully completing the ladder and subsequent difficulty maintaining regular lightly cooked egg in the diet. These families continued egg as an ingredient in cooked or baked food.There were some limitations to this study. Firstly, this was a retrospective small sized survey and some patients were unable to accurately recall timelines. As a voluntary survey there is also a risk of ascertainment bias. Baseline patient demographics (age, sex, SPT size, comorbid allergy diagnoses) of non-responders were compared to the study cohort with no significant differences identified. The initial education on commencing on the egg ladder was provided by multiple clinicians and information therefore was unable to be standardised. As expected, a number of patients at the time of the survey were still navigating the egg ladder and therefore had not had enough time to reach their individual threshold to determine if their child had outgrown their allergy. This may lead to under-reporting of egg tolerance on the ladder. Finally, follow up or assistance with the egg ladder was not provided unless the parent contacted the team. This may have resulted in less children completing the ladder due to parental anxiety over mild reactions.We have shown that the use of a structured egg ladder for egg allergic children without a history of anaphylaxis can be safe, is well tolerated and is a positive experience for families. It can prevent time consuming and costly inpatient supervised challenges unnecessarily consuming valuable and scarce resources in busy allergy clinics. Future prospective studies will help establish the role of home egg introduction in childhood egg allergy management in both tertiary and secondary health care settings.Conflicts of InterestNo conflicts to be declared.Leah Thomas1Jan Belcher1Rachael Phillips1Kahn Preece, MBBS, FRACP1Rani Bhatia, MBBS, FRACP11Department of Paediatric Allergy and Immunology, John Hunter Children’s Hospital, Newcastle, AustraliaReferences1. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. Journal of Allergy and Clinical Immunology. 2011;127:668-76.2. Dang TD, Peters RL, Koplin JJ, et al. Egg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts. Allergy. 2019; 74: 2.3. Gotesdyner L, Zeldin Y et al. A structured graduated protocol with heat denatured eggs in the treatment of egg allergy. Pediatric Allergy and Immunology. 2019;30:824-832.4. Leonard SA, Sampson HA, Sicerer SH, et al. Dietary baked egg accelerates resolution of egg allergy in children. Journal of Allergy and Clinical Immunology. 2012;13:2.5. Turner PJ, Mehr S, Joshi P et al. Safety to food challenges to extensively heated egg in egg-allergic children: a prospective cohort study. Pediatric Allergy and Immunology. 2013;24:450-455.6. Clark A, Islam S, King Y. A longitudinal study of resolution of allergy to well-cooked and uncooked egg. Clinical & Experimental Allergy. 2011;41:706-712.7 Lambert R, Grimshaw K, Elis B et al. Evidence that eating baked egg or milk influences egg or milk allergy resolution: A Systematic Review. Clin Exp Allergy. 2017;47(6):829-837.8. Upton J, Nowak-Wegrzyn A. The impact of baked egg and baked milk diets on IgE and Non-IgE mediated allergy. Clinical Reviews in Allergy & Immunology. 2018;55(2):118-138.9. Leonard SA, Caubet JC, Kim, JS, Groetch M, Wegrzyn AN. Baked Milk- and Egg-Containing Diet in the Management of Milk and Egg Allergy. Journal of Allergy and Clinical Immunology. 2015;1:13 – 23.

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